Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Proximal Nephron

Jia L. Zhuo, Xiao C. Li

10.1002/cphy.c110061

Source: Volume 3, Issue 3, July 2013

Published online: July 2013

Full Article on Wiley Online Library



Abstract

The kidney plays a fundamental role in maintaining body salt and fluid balance and blood pressure homeostasis through the actions of its proximal and distal tubular segments of nephrons. However, proximal tubules are well recognized to exert a more prominent role than distal counterparts. Proximal tubules are responsible for reabsorbing approximately 65% of filtered load and most, if not all, of filtered amino acids, glucose, solutes, and low molecular weight proteins. Proximal tubules also play a key role in regulating acid‐base balance by reabsorbing approximately 80% of filtered bicarbonate. The purpose of this review article is to provide a comprehensive overview of new insights and perspectives into current understanding of proximal tubules of nephrons, with an emphasis on the ultrastructure, molecular biology, cellular and integrative physiology, and the underlying signaling transduction mechanisms. The review is divided into three closely related sections. The first section focuses on the classification of nephrons and recent perspectives on the potential role of nephron numbers in human health and diseases. The second section reviews recent research on the structural and biochemical basis of proximal tubular function. The final section provides a comprehensive overview of new insights and perspectives in the physiological regulation of proximal tubular transport by vasoactive hormones. In the latter section, attention is particularly paid to new insights and perspectives learnt from recent cloning of transporters, development of transgenic animals with knockout or knockin of a particular gene of interest, and mapping of signaling pathways using microarrays and/or physiological proteomic approaches. © 2013 American Physiological Society. Compr Physiol 3:1079‐1123, 2013.

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images


Figure 1. Figure 1.

Classification and localization of superficial (short‐looped, upper) and juxtamedullary (long‐looped, lower) nephrons, together with the collecting system. The cortical medullary ray is the part of the cortex that contains the straight proximal tubules, cortical thick ascending limbs, and cortical collecting ducts, delineated by a dashed line. 1, renal corpuscle (Bowman's capsule and the glomerulus); 2, proximal convoluted tubule; 3, proximal straight tubule; 4, descending thin limb; 5, ascending thin limb; 6, thick ascending limb; 7, macula densa (located within the final portion of the thick ascending limb); 8, distal convoluted tubule; 9, connecting tubule; 9*, connecting tubule of a juxtamedullary nephron that arches upward to form a so‐called arcade (there are only a few of these in the human kidney); 10, cortical collecting duct; 11, outer medullary collecting duct; and 12, inner medullary collecting duct. Reproduced, with permission, from Kriz W and Bankir L. (290).
Figure 2. Figure 2.

Schematic location and ultrastructure of proximal tubular S1‐S3 segments in superficial and juxtamedullary neprhons. For superficial nephrons, S1 segments begin at the urinary pole of the renal corpuscle in the superficial cortex, transform gradually to S2 segments within the labyrinth, and S2 are transformed at different levels within the medullary rays. S3 segments terminate at the border of the outer stripe (OS) to the inner stripe. For juxtamedullary nephrons, S1 and S2 segments start at the urinary pole of the renal corpuscle in the inner cortex, and S3 segments also terminate at the border of the OS to the inner stripe. (A) The S1 segment has the most extensive cellular interdigitation and dense brush border membranes. (B) The vacuolar apparatus in the subapical cytoplasm, mitochondria, endoplasmic reticulum (ER), Golgi apparatus, lysosomes, and peroxisomes in proximal tubule cells. (C) The rabbit has tallest brush border microvilli in proximal tubule cells. (D) Many other species shows shortest microvilli in proximal tubule cells. Reproduced from Kriz and Kaissling, with permission (291).
Figure 3. Figure 3.

Low‐resolution profiles and ultrastructures of proximal tubules in the rat kidney. (A) Profiles of S1, S2, and S3 segments of juxtamedullary proximal tubules with different brush border heights, cytoplasmic density, and outer diameters. Magnification: X ∼1000. (B) Ultrastructures of S1, S2, and S3 proximal tubular cells in the rat kidney. Note that the mitochondria in S1 and S2 are located in lateral cell processes, whereas in S3 they are mainly scattered throughout the cytoplasm. The endocytic apparatus is the subapical cytoplasm is most prominent in S1 and S2 segments (broken lines), whereas endosomes (stars) and lysosomes (L) are localized deeper in the cytoplasm. There are few vacuolar apparatus and lysosomes present in the S3 segment, but peroxisomes (P) are more frequent in this segment. C, capillaries. Magnification: X ∼5400 from transmission electron microscopy. Reproduced from Kriz & Kaissling, with permission, (290).
Figure 4. Figure 4.

Localization of Na+‐K+‐ATPase α1‐ and γ‐subunits and aquaporin‐1 (AQP1) in the renal cortex. AQP1 was used as a marker of proximal tubule. Kidney cortex was triple labeled with α1‐ (red, TSA‐Cy3), AQP1 (green, FITC), and γ‐subunit (blue, Cy5) antibodies. Proximal segments (PCT) containing AQP1 stain were lightly labeled with α1‐ and γ‐subunits (bottom right: merged image). Conversely, distal segments (DCT) that were not labeled by the AQP1 antibody were brightly stained by α1‐ and γ‐subunits (bottom right: merged image). Scale bar, 50 μm. Reproduced from Wetzel and Sweadner, with permission (543).
Figure 5. Figure 5.

Localization and redistribution of NHE3 during acute hypertension. The endocytic compartment of the proximal tubule was labeled by intravenous injection of horseradish peroxidase (HRP), and rats were sham operated (control), or blood pressure was increased for 20 min (acute hypertension). Kidneys were fixed in situ, sectioned, and double labeled with either polyclonal anti‐NHE3 or monoclonal anti‐HRP (red). NHE3 is retracted from the body to the base of the microvilli during acute hypertension, with no evidence that NHE3 moves into endocytic tracer HRP‐labeled compartment. Reproduced from McDonough, with permission (343).
Figure 6. Figure 6.

Effects of 2 week infusion of a pressor dose of ANG II and concurrent losartan treatment on phosphorylated or activated NHE3 immunofluorescence staining (A‐C, not quantitative) or phospho‐NHE3 protein abundance in membrane fractions of proximal tubules of the rat kidney (semiquantitative). One hundred microgram proteins were loaded in each lane of Western blot gels. *, p < 0.05 or ** p < 0.01 versus control; †† p < 0.01 versuss ANG II‐infused rats. Reproduced from Li and Zhuo (313).
Figure 7. Figure 7.

Effects of 2 week infusion of the nonpressor dose of ANG II and concurrent losartan treatment on phosphorylated NHE3 immunofluorescence staining (A‐C, not quantitative) or phospho‐NHE3 protein abundance in membrane fractions of proximal tubules of the rat kidney (semiquantitative). One hundred microgram proteins were loaded in each lane of Western blot gels. *, p < 0.05 or **, p < 0.01 versus control; ††, p < 0.01 versus ANG II‐infused rats. Reproduced from Li and Zhuo, with permission (313).
Figure 8. Figure 8.

Effects of global NHE3 gene knockout on proximal tubule fluid and bicarbonate absorption and blood pressure in adult Slc9a3+/+ [wild type (WT)] and Slc9a3 −/− (NHE‐3 knockout) mice. (A and B) In situ microperfusion of proximal convoluted tubules revealed that fluid (A) and HCO3 − (B) absorption were sharply reduced in Slc9a3 −/− tubules (n = 14) relative to Slc9a3 +/+ tubules (n = 12). **, p < 0.001; Jv, fluid absorption; JHCO3, HCO3 − absorption. (C) Blood‐pressure measurements using the tail‐cuff method showed that systolic pressure was significantly reduced in awake Slc9a3 −/− mice (*, p < 0.05, n = 4 for each genotype). (D) Blood‐pressure measurements using a femoral artery catheter showed that mean arterial pressure was reduced (*, p < 0.05) in anaesthetized Slc9a3 −/− mice (n = 12) compared with both Slc9a3 +/− (n = 7) and Slc9a3 +/+ (n = 10) mice. Values for all analyses are mean SEM. Reproduced from Schultheis et al., with permission (451).
Figure 9. Figure 9.

Localization of the sodium and glucose cotransporter 2 (SGLT2) mRNAs in the kidney tubules by in situ hybridization. (A) Low‐power micrograph showing the pattern of hybridization of Hu 14 antisense cRNA probe (35S‐labeled) to rat kidney cryosections. A strong hybridization is detected over tubules in the cortex (C), whereas the signal is absent in outer medulla (OM), inner medulla (IM), and papilla (P). (B‐D) Sequential 5 μm sections of rat kidney cortex hybridized with Hu14 antisense cRNA probe (B) or stained with antibodies against the S1 segment specific marker GLUT2 (C) or carbonic anhydrase IV (D), which is specific for S2 segments of proximal tubules and the thick ascending limbs of Henle's loop. A strong hybridization signal is evident in B and is localized over tubules that show a basolateral staining for GLUT2 (indicated as S1 in C). In contrast, carbonic anhydrase IV positive tubules (indicated as S2 in D) do not contain a Hu14 hybridization signal. The S3 segment‐specific antiecto ATPase antibody did not stain tubules in the field corresponding to B and ecto‐ATPase‐positive tubules detected in other areas of the kidney did not contain Hu14 hybridization signal (not shown). Bar, 0.4 mm (A) and 0.1 mm (B‐D). Reproduced from Kenai et al., with permission (259).
Figure 10. Figure 10.

Effects of SGLT2 knockout on glucose reabsorption in the early proximal tubule of SGLT2−/− mice, as revealed by in vivo micropuncture studies under anesthesia. (A) Free‐flow collections of tubular fluid are performed along accessible proximal tubules at the kidney surface to establish a profile for FR glucose versus FR fluid. (B and C) Mean FR glucose (B) and fractional reabsorption of chloride (C) for early (FR fluid <40%) and late (FR fluid ≥40%) proximal tubular collections and up to the urine (n = 18 to 23 nephrons in four to five mice). *, p < 0.001 versus wild type (WT) mice. Reproduced from Vallon et al., with permission (516).
Figure 11. Figure 11.

(A‐E) Effect of intracellular microinjection of ANG II (1 nmol/L, ∼70‐100 fl) on [Ca2+]i responses in single proximal tubule cells at baseline (0 s) and 15, 30, 60, and 120 s after microinjection of Ang II in the cells. (F) Relative levels of [Ca2+]i signaling before and after microinjection of Ang II. Red represents the highest level of [Ca2+]i responses, whereas black is the background. **, p < 0.01 versus basal. Reproduced from Zhuo et al., with permission (592).
Figure 12. Figure 12.

Model of acid‐base transport in the proximal tubule (PT). The PT reabsorbs HCO3− by using active‐transport processes to secrete H+ into the tubule lumen and titrating HCO3− to CO2 and H2O. Thus, HCO3− reabsorption requires CO2 uptake across the apical membrane. Once inside the cell, CO2 and H2O recombine to regenerate HCO3−, which exits across the basolateral membrane. NHE3, Na‐H exchanger 3; AQP1, aquaporin 1; CA II and CA IV, carbonic anhydrases II and IV; NBCe1‐A, electrogenic Na/HCO3 co‐transporter 1, splice variant A. Reproduced from Boron, with permission (59).
Figure 13. Figure 13.

Osmolality in plasma and late proximal tubular (LPT) fluid in aquaporin‐1 (AQP1)‐knockout (−/−) and wild‐type (+/+) mice. Values are means ± SE and are shown for AQP1 +/+ (n = 21 nephrons in four mice), AQP1 −/− (n = 24/5), and hydrated AQP1 −/− mice (n = 19/3). (A) Relationship between absolute values of osmolalities in plasma and late proximal tubule fluid (where SE bars cannot be seen, they are smaller than the symbol used). (B) Transtubular osmotic gradients, that is, the osmolality differences (Δ) between plasma and LPT. *, p < 0.001 compared with AQP1 +/+ mice. Reproduced from Vallon et al., with permission (517).
Figure 14. Figure 14.

Normal renal handling of lithium reabsorption in proximal tubules in comparison with those of inulin, sodium and water in rodents and humans with a normal sodium intake. Data are drawn from Refs. (449,463,495,496).
Figure 15. Figure 15.

A schematic diagram showing physical, intraluminal, and humoral factors that regulate glomerulotubular balance (GTB). ⊕, increase. Ø, decrease.
Figure 16. Figure 16.

in vitro autoradiographic mapping of: (A) active renin binding in justaglomerular apparatus in the dog kidney pretreated with sodium depletion using the radiolabeled renin inhibitor, 125I‐H77, (B) angiotensin I‐converting enzyme binding in proximal tubules of the rat kidney using 125I‐351A, (C) AT1 receptor in the presence of the AT2 receptor blocker PD123319 or (D) AT2 receptor binding in the presence of the AT1 receptor blocker losartan using 125I‐[Sar1,Ile8]‐ANG II, (E) ANG (1‐7) receptor binding in the rat kidney using 125I‐ANG (1‐7) as the radioligand, and (F) ANG IV receptor binding in the rat kidney using 125I‐ANG (3‐8). The levels of binding are indicated by color calibration bars with red representing the highest, whereas blue showing the lowest levels of enzyme or receptor binding. G: glomerulus. IM: inner medulla. IS: inner stripe of the outer medulla. JGA: juxtaglomerular apparatus. P: proximal tubule. Reproduced from Zhuo and Li, with permission (591).
Figure 17. Figure 17.

A schematic representation of local generation of ANG II in proximal tubules of the kidney and its role in the regulation of proximal tubular reabsorption and glomerulotubular balance (GTB). ⊕, stimulation. Ø, inhibition.
Figure 18. Figure 18.

Schematic depiction of dopamine formation and cell signaling mechanisms activating sodium transport across the proximal renal tubule cell. DA indicates dopamine; D1R, dopamine D1 receptor; PLC, phospholipase C; DAG, diacylglycerol; and AC, adenylyl cyclase. Reproduced from Carey, with permission (81).
Figure 19. Figure 19.

A schematic diagram showing GRK4 and renal dopamine and ANG II type 1 receptor interactions to regulate renal tubular transport and blood pressure homeostasis. During conditions of moderately increased NaCl intake, the renal D1R is stimulated by dopamine produced in the kidney. The D1R or D3R, whose coupling to G protein subunits is regulated by G protein‐coupled receptor kinase type 4 (GRK4), inhibits sodium reabsorption in several nephron segments. This results in an increase in sodium excretion and maintenance of normal blood pressure. GRK4 wild‐type (GRK4 WT) also negatively regulates AT1R transcription. The decrease in AT1R expression, caused by GRK4 WT, facilitates the inhibitory effect of D1R on renal sodium transport. In essential hypertension, constitutively active variants of GRK4 not only uncouple D1R and D3R from G protein subunits, but also increase AT1R transcription in the kidney. These effects impair the ability of the kidney to excrete the excess sodium load, resulting in sodium retention, and ultimately hypertension. Green box, normal coupling of D1R and D3R to G protein subunits; red box, uncoupling of D1R and D3R from G protein subunits. Green arrows, stimulatory; red arrows, inhibitory. Reproduced from Jose, with permission (254).
Figure 20. Figure 20.

The intrarenal distribution of atrial natriuretic factor (ANF) receptors in the rat kidney, as visualized by quantitative in vitro autoradiography using [125I]‐labeled ANF as the radioligand. High levels of ANF receptor binding occur in the glomeruli (G) and the inner medulla (IM), whereas moderate levels of ANF binding are seen in the proximal convoluted tubules (PCT) and inner stripe of the outer medulla (VRB). Red represents highest whereas black the lowest levels of ANF receptor binding. Reproduced from Zhuo and Mendelsohn, with permission (583).
Figure 21. Figure 21.

Schematic representation of potential multilevel interactions between ANF and ANG II to regulate renal hemodynamics and proximal tubular transport of sodium and fluid in the kidney. A, afferent arteriole. E, efferent arteriole. AI, ANG I. AII, ANG II. CE, converting enzyme. CEI, converting enzyme inhibitor. Kf, ultrafiltration coefficient. ⊕, stimulation or increase. Ø, inhibition or decrease.
Figure 22. Figure 22.

The intrarenal distribution of endothelin 1 (ET‐1) receptors in the rat kidney, as visualized by quantitative in vitro autoradiography using [125I]‐endothelin 1 as the radioligand. High levels of ET‐1 receptor binding occur in the inner medulla (IM) and glomeruli (G), whereas moderate levels of ET‐1 binding are seen in the proximal convoluted tubules (PCT) and inner stripe of the outer medulla (VRB). Red represents highest whereas black the lowest levels of ET‐1 receptor binding. Reproduced from Zhuo and Mendelsohn, with permission (580,583).
Figure 23. Figure 23.

Relationship between the rates of single nephron GFR (SNGFR) and proximal tubular fluid reabsorption of WT, ACE 2/2, and ACE 1/3 mice during control (top) and during angiotensin II infusion (bottom). Lines are linear regression lines calculated for the range of the data. Reproduced from Hashimoto et al., with permission (206).
Figure 24. Figure 24.

Expression of an intracellular cyan fluorescent fusion of ANG II, ECFP/ANG II, selectively in freshly isolated proximal tubules of the rat kidney 2 weeks after intrarenal ECFP/ANG II transfer. The sodium and glucose cotransporter 2 (SGLT2) gene promoter was used to drive ECFP/ANG II expression selectively in proximal tubules of the kidney. Bars = 10 μm for the proximal tubule or 30 μm for the glomerulus. Reproduced from Li et al., with permission (310).
Figure 25. Figure 25.

Effects of proximal tubule‐specific transfer of ECFP/ANG II or its scrambled control, ECFP/ANG IIc, with or without losartan treatment on systolic blood pressure in rats (SBP; A) or ECFP/ANG II transfer in wild‐type or AT1a‐KO mice (B). *, p < 0.05 or **, p < 0.01 versus basal SBP. +, p < 0.05 or ++, p < 0.01 versus SBP in ECFP/ANG II‐transferred rats. #, p < 0.05 or ++ p < 0.01 versus SBP in wild‐type mice at basal or 2 weeks after intrarenal ECFP/ANG II transfer. Reproduced from Li et al., with permission (310).


Figure 1.

Classification and localization of superficial (short‐looped, upper) and juxtamedullary (long‐looped, lower) nephrons, together with the collecting system. The cortical medullary ray is the part of the cortex that contains the straight proximal tubules, cortical thick ascending limbs, and cortical collecting ducts, delineated by a dashed line. 1, renal corpuscle (Bowman's capsule and the glomerulus); 2, proximal convoluted tubule; 3, proximal straight tubule; 4, descending thin limb; 5, ascending thin limb; 6, thick ascending limb; 7, macula densa (located within the final portion of the thick ascending limb); 8, distal convoluted tubule; 9, connecting tubule; 9*, connecting tubule of a juxtamedullary nephron that arches upward to form a so‐called arcade (there are only a few of these in the human kidney); 10, cortical collecting duct; 11, outer medullary collecting duct; and 12, inner medullary collecting duct. Reproduced, with permission, from Kriz W and Bankir L. (290).



Figure 2.

Schematic location and ultrastructure of proximal tubular S1‐S3 segments in superficial and juxtamedullary neprhons. For superficial nephrons, S1 segments begin at the urinary pole of the renal corpuscle in the superficial cortex, transform gradually to S2 segments within the labyrinth, and S2 are transformed at different levels within the medullary rays. S3 segments terminate at the border of the outer stripe (OS) to the inner stripe. For juxtamedullary nephrons, S1 and S2 segments start at the urinary pole of the renal corpuscle in the inner cortex, and S3 segments also terminate at the border of the OS to the inner stripe. (A) The S1 segment has the most extensive cellular interdigitation and dense brush border membranes. (B) The vacuolar apparatus in the subapical cytoplasm, mitochondria, endoplasmic reticulum (ER), Golgi apparatus, lysosomes, and peroxisomes in proximal tubule cells. (C) The rabbit has tallest brush border microvilli in proximal tubule cells. (D) Many other species shows shortest microvilli in proximal tubule cells. Reproduced from Kriz and Kaissling, with permission (291).



Figure 3.

Low‐resolution profiles and ultrastructures of proximal tubules in the rat kidney. (A) Profiles of S1, S2, and S3 segments of juxtamedullary proximal tubules with different brush border heights, cytoplasmic density, and outer diameters. Magnification: X ∼1000. (B) Ultrastructures of S1, S2, and S3 proximal tubular cells in the rat kidney. Note that the mitochondria in S1 and S2 are located in lateral cell processes, whereas in S3 they are mainly scattered throughout the cytoplasm. The endocytic apparatus is the subapical cytoplasm is most prominent in S1 and S2 segments (broken lines), whereas endosomes (stars) and lysosomes (L) are localized deeper in the cytoplasm. There are few vacuolar apparatus and lysosomes present in the S3 segment, but peroxisomes (P) are more frequent in this segment. C, capillaries. Magnification: X ∼5400 from transmission electron microscopy. Reproduced from Kriz & Kaissling, with permission, (290).



Figure 4.

Localization of Na+‐K+‐ATPase α1‐ and γ‐subunits and aquaporin‐1 (AQP1) in the renal cortex. AQP1 was used as a marker of proximal tubule. Kidney cortex was triple labeled with α1‐ (red, TSA‐Cy3), AQP1 (green, FITC), and γ‐subunit (blue, Cy5) antibodies. Proximal segments (PCT) containing AQP1 stain were lightly labeled with α1‐ and γ‐subunits (bottom right: merged image). Conversely, distal segments (DCT) that were not labeled by the AQP1 antibody were brightly stained by α1‐ and γ‐subunits (bottom right: merged image). Scale bar, 50 μm. Reproduced from Wetzel and Sweadner, with permission (543).



Figure 5.

Localization and redistribution of NHE3 during acute hypertension. The endocytic compartment of the proximal tubule was labeled by intravenous injection of horseradish peroxidase (HRP), and rats were sham operated (control), or blood pressure was increased for 20 min (acute hypertension). Kidneys were fixed in situ, sectioned, and double labeled with either polyclonal anti‐NHE3 or monoclonal anti‐HRP (red). NHE3 is retracted from the body to the base of the microvilli during acute hypertension, with no evidence that NHE3 moves into endocytic tracer HRP‐labeled compartment. Reproduced from McDonough, with permission (343).



Figure 6.

Effects of 2 week infusion of a pressor dose of ANG II and concurrent losartan treatment on phosphorylated or activated NHE3 immunofluorescence staining (A‐C, not quantitative) or phospho‐NHE3 protein abundance in membrane fractions of proximal tubules of the rat kidney (semiquantitative). One hundred microgram proteins were loaded in each lane of Western blot gels. *, p < 0.05 or ** p < 0.01 versus control; †† p < 0.01 versuss ANG II‐infused rats. Reproduced from Li and Zhuo (313).



Figure 7.

Effects of 2 week infusion of the nonpressor dose of ANG II and concurrent losartan treatment on phosphorylated NHE3 immunofluorescence staining (A‐C, not quantitative) or phospho‐NHE3 protein abundance in membrane fractions of proximal tubules of the rat kidney (semiquantitative). One hundred microgram proteins were loaded in each lane of Western blot gels. *, p < 0.05 or **, p < 0.01 versus control; ††, p < 0.01 versus ANG II‐infused rats. Reproduced from Li and Zhuo, with permission (313).



Figure 8.

Effects of global NHE3 gene knockout on proximal tubule fluid and bicarbonate absorption and blood pressure in adult Slc9a3+/+ [wild type (WT)] and Slc9a3 −/− (NHE‐3 knockout) mice. (A and B) In situ microperfusion of proximal convoluted tubules revealed that fluid (A) and HCO3 − (B) absorption were sharply reduced in Slc9a3 −/− tubules (n = 14) relative to Slc9a3 +/+ tubules (n = 12). **, p < 0.001; Jv, fluid absorption; JHCO3, HCO3 − absorption. (C) Blood‐pressure measurements using the tail‐cuff method showed that systolic pressure was significantly reduced in awake Slc9a3 −/− mice (*, p < 0.05, n = 4 for each genotype). (D) Blood‐pressure measurements using a femoral artery catheter showed that mean arterial pressure was reduced (*, p < 0.05) in anaesthetized Slc9a3 −/− mice (n = 12) compared with both Slc9a3 +/− (n = 7) and Slc9a3 +/+ (n = 10) mice. Values for all analyses are mean SEM. Reproduced from Schultheis et al., with permission (451).



Figure 9.

Localization of the sodium and glucose cotransporter 2 (SGLT2) mRNAs in the kidney tubules by in situ hybridization. (A) Low‐power micrograph showing the pattern of hybridization of Hu 14 antisense cRNA probe (35S‐labeled) to rat kidney cryosections. A strong hybridization is detected over tubules in the cortex (C), whereas the signal is absent in outer medulla (OM), inner medulla (IM), and papilla (P). (B‐D) Sequential 5 μm sections of rat kidney cortex hybridized with Hu14 antisense cRNA probe (B) or stained with antibodies against the S1 segment specific marker GLUT2 (C) or carbonic anhydrase IV (D), which is specific for S2 segments of proximal tubules and the thick ascending limbs of Henle's loop. A strong hybridization signal is evident in B and is localized over tubules that show a basolateral staining for GLUT2 (indicated as S1 in C). In contrast, carbonic anhydrase IV positive tubules (indicated as S2 in D) do not contain a Hu14 hybridization signal. The S3 segment‐specific antiecto ATPase antibody did not stain tubules in the field corresponding to B and ecto‐ATPase‐positive tubules detected in other areas of the kidney did not contain Hu14 hybridization signal (not shown). Bar, 0.4 mm (A) and 0.1 mm (B‐D). Reproduced from Kenai et al., with permission (259).



Figure 10.

Effects of SGLT2 knockout on glucose reabsorption in the early proximal tubule of SGLT2−/− mice, as revealed by in vivo micropuncture studies under anesthesia. (A) Free‐flow collections of tubular fluid are performed along accessible proximal tubules at the kidney surface to establish a profile for FR glucose versus FR fluid. (B and C) Mean FR glucose (B) and fractional reabsorption of chloride (C) for early (FR fluid <40%) and late (FR fluid ≥40%) proximal tubular collections and up to the urine (n = 18 to 23 nephrons in four to five mice). *, p < 0.001 versus wild type (WT) mice. Reproduced from Vallon et al., with permission (516).



Figure 11.

(A‐E) Effect of intracellular microinjection of ANG II (1 nmol/L, ∼70‐100 fl) on [Ca2+]i responses in single proximal tubule cells at baseline (0 s) and 15, 30, 60, and 120 s after microinjection of Ang II in the cells. (F) Relative levels of [Ca2+]i signaling before and after microinjection of Ang II. Red represents the highest level of [Ca2+]i responses, whereas black is the background. **, p < 0.01 versus basal. Reproduced from Zhuo et al., with permission (592).



Figure 12.

Model of acid‐base transport in the proximal tubule (PT). The PT reabsorbs HCO3− by using active‐transport processes to secrete H+ into the tubule lumen and titrating HCO3− to CO2 and H2O. Thus, HCO3− reabsorption requires CO2 uptake across the apical membrane. Once inside the cell, CO2 and H2O recombine to regenerate HCO3−, which exits across the basolateral membrane. NHE3, Na‐H exchanger 3; AQP1, aquaporin 1; CA II and CA IV, carbonic anhydrases II and IV; NBCe1‐A, electrogenic Na/HCO3 co‐transporter 1, splice variant A. Reproduced from Boron, with permission (59).



Figure 13.

Osmolality in plasma and late proximal tubular (LPT) fluid in aquaporin‐1 (AQP1)‐knockout (−/−) and wild‐type (+/+) mice. Values are means ± SE and are shown for AQP1 +/+ (n = 21 nephrons in four mice), AQP1 −/− (n = 24/5), and hydrated AQP1 −/− mice (n = 19/3). (A) Relationship between absolute values of osmolalities in plasma and late proximal tubule fluid (where SE bars cannot be seen, they are smaller than the symbol used). (B) Transtubular osmotic gradients, that is, the osmolality differences (Δ) between plasma and LPT. *, p < 0.001 compared with AQP1 +/+ mice. Reproduced from Vallon et al., with permission (517).



Figure 14.

Normal renal handling of lithium reabsorption in proximal tubules in comparison with those of inulin, sodium and water in rodents and humans with a normal sodium intake. Data are drawn from Refs. (449,463,495,496).



Figure 15.

A schematic diagram showing physical, intraluminal, and humoral factors that regulate glomerulotubular balance (GTB). ⊕, increase. Ø, decrease.



Figure 16.

in vitro autoradiographic mapping of: (A) active renin binding in justaglomerular apparatus in the dog kidney pretreated with sodium depletion using the radiolabeled renin inhibitor, 125I‐H77, (B) angiotensin I‐converting enzyme binding in proximal tubules of the rat kidney using 125I‐351A, (C) AT1 receptor in the presence of the AT2 receptor blocker PD123319 or (D) AT2 receptor binding in the presence of the AT1 receptor blocker losartan using 125I‐[Sar1,Ile8]‐ANG II, (E) ANG (1‐7) receptor binding in the rat kidney using 125I‐ANG (1‐7) as the radioligand, and (F) ANG IV receptor binding in the rat kidney using 125I‐ANG (3‐8). The levels of binding are indicated by color calibration bars with red representing the highest, whereas blue showing the lowest levels of enzyme or receptor binding. G: glomerulus. IM: inner medulla. IS: inner stripe of the outer medulla. JGA: juxtaglomerular apparatus. P: proximal tubule. Reproduced from Zhuo and Li, with permission (591).



Figure 17.

A schematic representation of local generation of ANG II in proximal tubules of the kidney and its role in the regulation of proximal tubular reabsorption and glomerulotubular balance (GTB). ⊕, stimulation. Ø, inhibition.



Figure 18.

Schematic depiction of dopamine formation and cell signaling mechanisms activating sodium transport across the proximal renal tubule cell. DA indicates dopamine; D1R, dopamine D1 receptor; PLC, phospholipase C; DAG, diacylglycerol; and AC, adenylyl cyclase. Reproduced from Carey, with permission (81).



Figure 19.

A schematic diagram showing GRK4 and renal dopamine and ANG II type 1 receptor interactions to regulate renal tubular transport and blood pressure homeostasis. During conditions of moderately increased NaCl intake, the renal D1R is stimulated by dopamine produced in the kidney. The D1R or D3R, whose coupling to G protein subunits is regulated by G protein‐coupled receptor kinase type 4 (GRK4), inhibits sodium reabsorption in several nephron segments. This results in an increase in sodium excretion and maintenance of normal blood pressure. GRK4 wild‐type (GRK4 WT) also negatively regulates AT1R transcription. The decrease in AT1R expression, caused by GRK4 WT, facilitates the inhibitory effect of D1R on renal sodium transport. In essential hypertension, constitutively active variants of GRK4 not only uncouple D1R and D3R from G protein subunits, but also increase AT1R transcription in the kidney. These effects impair the ability of the kidney to excrete the excess sodium load, resulting in sodium retention, and ultimately hypertension. Green box, normal coupling of D1R and D3R to G protein subunits; red box, uncoupling of D1R and D3R from G protein subunits. Green arrows, stimulatory; red arrows, inhibitory. Reproduced from Jose, with permission (254).



Figure 20.

The intrarenal distribution of atrial natriuretic factor (ANF) receptors in the rat kidney, as visualized by quantitative in vitro autoradiography using [125I]‐labeled ANF as the radioligand. High levels of ANF receptor binding occur in the glomeruli (G) and the inner medulla (IM), whereas moderate levels of ANF binding are seen in the proximal convoluted tubules (PCT) and inner stripe of the outer medulla (VRB). Red represents highest whereas black the lowest levels of ANF receptor binding. Reproduced from Zhuo and Mendelsohn, with permission (583).



Figure 21.

Schematic representation of potential multilevel interactions between ANF and ANG II to regulate renal hemodynamics and proximal tubular transport of sodium and fluid in the kidney. A, afferent arteriole. E, efferent arteriole. AI, ANG I. AII, ANG II. CE, converting enzyme. CEI, converting enzyme inhibitor. Kf, ultrafiltration coefficient. ⊕, stimulation or increase. Ø, inhibition or decrease.



Figure 22.

The intrarenal distribution of endothelin 1 (ET‐1) receptors in the rat kidney, as visualized by quantitative in vitro autoradiography using [125I]‐endothelin 1 as the radioligand. High levels of ET‐1 receptor binding occur in the inner medulla (IM) and glomeruli (G), whereas moderate levels of ET‐1 binding are seen in the proximal convoluted tubules (PCT) and inner stripe of the outer medulla (VRB). Red represents highest whereas black the lowest levels of ET‐1 receptor binding. Reproduced from Zhuo and Mendelsohn, with permission (580,583).



Figure 23.

Relationship between the rates of single nephron GFR (SNGFR) and proximal tubular fluid reabsorption of WT, ACE 2/2, and ACE 1/3 mice during control (top) and during angiotensin II infusion (bottom). Lines are linear regression lines calculated for the range of the data. Reproduced from Hashimoto et al., with permission (206).



Figure 24.

Expression of an intracellular cyan fluorescent fusion of ANG II, ECFP/ANG II, selectively in freshly isolated proximal tubules of the rat kidney 2 weeks after intrarenal ECFP/ANG II transfer. The sodium and glucose cotransporter 2 (SGLT2) gene promoter was used to drive ECFP/ANG II expression selectively in proximal tubules of the kidney. Bars = 10 μm for the proximal tubule or 30 μm for the glomerulus. Reproduced from Li et al., with permission (310).



Figure 25.

Effects of proximal tubule‐specific transfer of ECFP/ANG II or its scrambled control, ECFP/ANG IIc, with or without losartan treatment on systolic blood pressure in rats (SBP; A) or ECFP/ANG II transfer in wild‐type or AT1a‐KO mice (B). *, p < 0.05 or **, p < 0.01 versus basal SBP. +, p < 0.05 or ++, p < 0.01 versus SBP in ECFP/ANG II‐transferred rats. #, p < 0.05 or ++ p < 0.01 versus SBP in wild‐type mice at basal or 2 weeks after intrarenal ECFP/ANG II transfer. Reproduced from Li et al., with permission (310).

References
 1. Abuladze N, Lee I, Newman D, Hwang J, Pushkin A, Kurtz I. Axial heterogeneity of sodium‐bicarbonate cotransporter expression in the rabbit proximal tubule. Am J Physiol 274: F628‐F633, 1998.
 2. Adachi M, Yang YY, Furuichi Y, Miyamoto C. Cloning and characterization of cDNA encoding human A‐type endothelin receptor. Biochem Biophys Res Commun 180: 1265‐1272, 1991.
 3. Aizman O, Aperia A. Na,K‐ATPase as a signal transducer. Ann N Y Acad Sci 986: 489‐496, 2003.
 4. Albrecht FE, Drago J, Felder RA, Printz MP, Eisner GM, Robillard JE, Sibley DR, Westphal HJ, Jose PA. Role of the D1A dopamine receptor in the pathogenesis of genetic hypertension. J Clin Invest 97: 2283‐2288, 1996.
 5. Alpern RJ. Cell mechanisms of proximal tubule acidification. Physiol Rev 70: 79‐114, 1990.
 6. Alpern RJ, Chambers M. Cell pH in the rat proximal convoluted tubule. Regulation by luminal and peritubular pH and sodium concentration. J Clin Invest 78: 502‐510, 1986.
 7. Amemiya M, Kusano E, Muto S, Tabei K, Ando Y, Alpern RJ, Asano Y. Glucagon acutely inhibits but chronically activates Na(+)/H(+) antiporter 3 activity in OKP cells. Exp Nephrol 10: 26‐33, 2002.
 8. Amemiya M, Loffing J, Lotscher M, Kaissling B, Alpern RJ, Moe OW. Expression of NHE‐3 in the apical membrane of rat renal proximal tubule and thick ascending limb. Kidney Int 48: 1206‐1215, 1995.
 9. Ando R, Sasaki S, Shiigai T, Takeuchi J. Lack of effect of alpha‐human atrial natriuretic polypeptide on volume reabsorption and p‐aminohippuric acid secretion in the rabbit proximal straight tubule. Jpn J Physiol 37: 81‐91, 1987.
 10. Andreoli TE, Schafer JA, Troutman SL. Perfusion rate‐dependence of transepithelial osmosis in isolated proximal convoluted tubules: Estimation of the hydraulic conductance. Kidney Int 14: 263‐269, 1978.
 11. Aperia AC. Intrarenal dopamine: A key signal in the interactive regulation of sodium metabolism. Annu Rev Physiol 62: 621‐647, 2000.
 12. Arai H, Hori S, Aramori I, Ohkubo H, Nakanishi S. Cloning and expression of a cDNA encoding an endothelin receptor. Nature 348: 730‐732, 1990.
 13. Ardaillou R, Chansel D. Synthesis and effects of active fragments of angiotensin II. Kidney Int 52: 1458‐1468, 1997.
 14. Aronson PS. Mechanisms of active H+ secretion in the proximal tubule. Am J Physiol 245: F647‐F659, 1983.
 15. Aronson PS. Ion exchangers mediating Na+, HCO3− and Cl− transport in the renal proximal tubule. J Nephrol 19 Suppl 9: S3‐S10, 2006.
 16. Aronson PS, Nee J, Suhm MA. Modifier role of internal H+ in activating the Na+‐H+ exchanger in renal microvillus membrane vesicles. Nature 299: 161‐163, 1982.
 17. Aronson PS, Sacktor B. The Na+ gradient‐dependent transport of D‐glucose in renal brush border membranes. J Biol Chem 250: 6032‐6039, 1975.
 18. Asico LD, Ladines C, Fuchs S, Accili D, Carey RM, Semeraro C, Pocchiari F, Felder RA, Eisner GM, Jose PA. Disruption of the dopamine D3 receptor gene produces renin‐dependent hypertension. J Clin Invest 102: 493‐498, 1998.
 19. Attaphitaya S, Park K, Melvin JE. Molecular cloning and functional expression of a rat Na+/H+ exchanger (NHE5) highly expressed in brain. J Biol Chem 274: 4383‐4388, 1999.
 20. Avner ED, Sweeney WE Jr., Nelson WJ. Abnormal sodium pump distribution during renal tubulogenesis in congenital murine polycystic kidney disease. Proc Natl Acad Sci U S A 89: 7447‐7451, 1992.
 21. Bacic D, Kaissling B, McLeroy P, Zou L, Baum M, Moe OW. Dopamine acutely decreases apical membrane Na/H exchanger NHE3 protein in mouse renal proximal tubule. Kidney Int 64: 2133‐2141, 2003.
 22. Baines AD, de RC. Functional heterogeneity of nephrons. II. Filtration rates, intraluminal flow velocities and fractional water reabsorption. Pflugers Arch 308: 260‐276, 1969.
 23. Baird NR, Orlowski J, Szabo EZ, Zaun HC, Schultheis PJ, Menon AG, Shull GE. Molecular cloning, genomic organization, and functional expression of Na+/H+ exchanger isoform 5 (NHE5) from human brain. J Biol Chem 274: 4377‐4382, 1999.
 24. Bakris GL, Fonseca VA, Sharma K, Wright EM. Renal sodium‐glucose transport: Role in diabetes mellitus and potential clinical implications. Kidney Int 75: 1272‐1277, 2009.
 25. Banday AA, Lokhandwala MF. Angiotensin II‐mediated biphasic regulation of proximal tubular Na+/H+ exchanger 3 is impaired during oxidative stress. Am J Physiol Renal Physiol 301: F364‐F370, 2011.
 26. Bankir L, Farman N. Heterogeneity of the glomeruli in the rabbit. Arch Anat Microsc Morphol Exp 62: 281‐291, 1973.
 27. Banks RO. Effects of a physiological dose of ANP on renal function in dogs. Am J Physiol 255: F907‐F910, 1988.
 28. Barcroft LC, Moseley AE, Lingrel JB, Watson AJ. Deletion of the Na/K‐ATPase alpha1‐subunit gene (Atp1a1) does not prevent cavitation of the preimplantation mouse embryo. Mech Dev 121: 417‐426, 2004.
 29. Barfuss DW, Schafer JA. Collection and analysis of absorbate from proximal straight tubules. Am J Physiol 241: F597‐F604, 1981.
 30. Barfuss DW, Schafer JA. Differences in active and passive glucose transport along the proximal nephron. Am J Physiol 241: F322‐F332, 1981.
 31. Barfuss DW, Schafer JA. Rate of formation and composition of absorbate from proximal nephron segments. Am J Physiol 247: F117‐F129, 1984.
 32. Bartoli E, Conger JD, Earley LE. Effect of intraluminal flow on proximal tubular reabsorption. J Clin Invest 52: 843‐849, 1973.
 33. Bartoli E, Earley LE. Effects of saline infusion on glomerulotubular balance. Kidney Int 1: 67‐77, 1972.
 34. Basgen JM, Steffes MW, Stillman AE, Mauer SM. Estimating glomerular number in situ using magnetic resonance imaging and biopsy. Kidney Int 45: 1668‐1672, 1994.
 35. Baum M, Toto RD. Lack of a direct effect of atrial natriuretic factor in the rabbit proximal tubule. Am J Physiol 250: F66‐F69, 1986.
 36. Beck JC, Sacktor B. Membrane potential‐sensitive fluorescence changes during Na+‐dependent D‐glucose transport in renal brush border membrane vesicles. J Biol Chem 253: 7158‐7162, 1978.
 37. Beck JC, Sacktor B. The sodium electrochemical potential‐mediated uphill transport of D‐glucose in renal brush border membrane vesicles. J Biol Chem 253: 5531‐5535, 1978.
 38. Beeman SC, Zhang M, Gubhaju L, Wu T, Bertram JF, Frakes DH, Cherry BR, Bennett KM. Measuring glomerular number and size in perfused kidneys using MRI. Am J Physiol Renal Physiol 300: F1454‐F1457, 2011.
 39. Beguin P, Wang X, Firsov D, Puoti A, Claeys D, Horisberger JD, Geering K. The gamma subunit is a specific component of the Na,K‐ATPase and modulates its transport function. EMBO J 16: 4250‐4260, 1997.
 40. Bell TD, Luo Z, Welch WJ. Glomerular tubular balance is suppressed in adenosine type 1 receptor‐deficient mice. Am J Physiol Renal Physiol 299: F1158‐F1163, 2010.
 41. Berry CA. Water permeability and pathways in the proximal tubule. Am J Physiol 245: F279‐F294, 1983.
 42. Berry CA, Rector FC, Jr. Electroneutral NaCl absorption in the proximal tubule: Mechanisms of apical Na‐coupled transport. Kidney Int 36: 403‐411, 1989.
 43. Berry CA, Rector FC, Jr. Mechanism of proximal NaCl reabsorption in the proximal tubule of the mammalian kidney. Semin Nephrol 11: 86‐97, 1991.
 44. Bertram JF. Counting in the kidney. Kidney Int 59: 792‐796, 2001.
 45. Bertram JF, Soosaipillai MC, Ricardo SD, Ryan GB. Total numbers of glomeruli and individual glomerular cell types in the normal rat kidney. Cell Tissue Res 270: 37‐45, 1992.
 46. Bevensee MO, Boron WF. Control of intracellular pH. In: Alpern RJ, Hebert SC, editors. The Kidney: Physiology and Pathophysiology. Burlington, San Diego, and London: Academic Press, 2008. Chapter 51, pp. 1429‐1480.
 47. Bharatula M, Hussain T, Lokhandwala MF. Angiotensin II AT1 receptor/signaling mechanisms in the biphasic effect of the peptide on proximal tubular Na+, K+‐ATPase. Clin Exp Hypertens 20: 465‐480, 1998.
 48. Biemesderfer D, Pizzonia J, Abu‐Alfa A, Exner M, Reilly R, Igarashi P, Aronson PS. NHE3: a Na+/H+ exchanger isoform of renal brush border. Am J Physiol 265: F736‐F742, 1993.
 49. Biemesderfer D, Reilly RF, Exner M, Igarashi P, Aronson PS. Immunocytochemical characterization of Na+‐H+ exchanger isoform NHE‐1 in rabbit kidney. Am J Physiol 263: F833‐F840, 1992.
 50. Biemesderfer D, Rutherford PA, Nagy T, Pizzonia JH, bu‐Alfa AK, Aronson PS. Monoclonal antibodies for high‐resolution localization of NHE3 in adult and neonatal rat kidney. Am J Physiol 273: F289‐F299, 1997.
 51. Blantz RC. The glomerular and tubular actions of angiotensin II. Am J Kidney Dis 10: 2‐6, 1987.
 52. Blaustein MP. The interrelationship between sodium and calcium fluxes across cell membranes. Rev Physiol Biochem Pharmacol 70: 33‐82, 33‐82, 1974.
 53. Blaustein MP, Lederer WJ. Sodium/calcium exchange: Its physiological implications. Physiol Rev 79: 763‐854, 1999.
 54. Bloch RD, Zikos D, Fisher KA, Schleicher L, Oyama M, Cheng JC, Skopicki HA, Sukowski EJ, Cragoe EJ, Jr., Peterson DR. Activation of proximal tubular Na+‐H+ exchange by angiotensin II. Am J Physiol 263: F135‐F143, 1992.
 55. Bobulescu IA, Quinones H, Gisler SM, Di SF, Hu MC, Shi M, Zhang J, Fuster DG, Wright N, Mumby M, Moe OW. Acute regulation of renal Na+/H+ exchanger NHE3 by dopamine: role of protein phosphatase 2A. Am J Physiol Renal Physiol 298 (5): F1205‐13, 2010.
 56. Bojesen E, Leyssac PP. Proximal tubular reabsorption in the rat kidney as studied by the occlusion time and lissamine green transit time technique. Acta Physiol Scand 76: 213‐235, 1969.
 57. Bookstein C, Musch MW, DePaoli A, Xie Y, Villereal M, Rao MC, Chang EB. A unique sodium‐hydrogen exchange isoform (NHE‐4) of the inner medulla of the rat kidney is induced by hyperosmolarity. J Biol Chem 269: 29704‐29709, 1994.
 58. Borenstein HB, Cupples WA, Sonnenberg H, Veress AT. The effect of a natriuretic atrial extract on renal haemodynamics and urinary excretion in anaesthetized rats. J Physiol 334: 133‐140, 1983.
 59. Boron WF. Acid‐base transport by the renal proximal tubule. J Am Soc Nephrol 17: 2368‐2382, 2006.
 60. Boron WF, Boulpaep EL. The electrogenic Na/HCO3 cotransporter. Kidney Int 36: 392‐402, 1989.
 61. Brechue WF, Kinne‐Saffran E, Kinne RK, Maren TH. Localization and activity of renal carbonic anhydrase (CA) in CA‐II deficient mice. Biochim Biophys Acta 1066: 201‐207, 1991.
 62. Brenner BM, Bennett CM, Berliner RW. The relationship between glomerular filtration rate and sodium reabsorption by the proximal tubule of the rat nephron. J Clin Invest 47: 1358‐1374, 1968.
 63. Brenner BM, Garcia DL, Anderson S. Glomeruli and blood pressure. Less of one, more the other? Am J Hypertens 1: 335‐347, 1988.
 64. Brenner BM, Troy JL. Postglomerular vascular protein concentration: Evidence for a causal role in governing fluid reabsorption and glomerulotublar balance by the renal proximal tubule. J Clin Invest 50: 336‐349, 1971.
 65. Briggs JP, Steipe B, Schubert G, Schnermann J. Micropuncture studies of the renal effects of atrial natriuretic substance. Pflugers Arch 395: 271‐276, 1982.
 66. Brochner‐Mortensen J, Stockel M, Sorensen PJ, Nielsen AH, Ditzel J. Proximal glomerulo‐tubular balance in patients with type 1 (insulin‐dependent) diabetes mellitus. Diabetologia 27: 189‐192, 1984.
 67. Brown D, Zhu XL, Sly WS. Localization of membrane‐associated carbonic anhydrase type IV in kidney epithelial cells. Proc Natl Acad Sci U S A 87: 7457‐7461, 1990.
 68. Bruns FJ, Alexander EA, Riley AL, Levinsky NG. Superficial and juxtamedullary nephron function during saline loading in the dog. J Clin Invest 53: 971‐979, 1974.
 69. Buentig WE, Earley LE. Demonstration of independent roles of proximal tubular reabsorption and intratubular load in the phenomenon of glomerulotubular balance during aortic constriction in the rat. J Clin Invest 50: 77‐89, 1971.
 70. Burg M, Patlak C, Green N, Villey D. Organic solutes in fluid absorption by renal proximal convoluted tubules. Am J Physiol 231: 627‐637, 1976.
 71. Burg MB, Green N. Role of monovalent ions in the reabsorption of fluid by isolated perfused proximal renal tubules of the rabbit. Kidney Int 10: 221‐228, 1976.
 72. Burg MB, Orloff J. Control of fluid absorption in the renal proximal tubule. J Clin Invest 47: 2016‐2024, 1968.
 73. Burg MB, Orloff J. Electrical potential difference across proximal convoluted tubules. Am J Physiol 219: 1714‐1716, 1970.
 74. Burnett JC, Jr., Granger JP, Opgenorth TJ. Effects of synthetic atrial natriuretic factor on renal function and renin release. Am J Physiol 247: F863‐F866, 1984.
 75. Burnett JC, Jr., Opgenorth TJ, Granger JP. The renal action of atrial natriuretic peptide during control of glomerular filtration. Kidney Int 30: 16‐19, 1986.
 76. Camargo MJ, Kleinert HD, Atlas SA, Sealey JE, Laragh JH, Maack T. Ca‐dependent hemodynamic and natriuretic effects of atrial extract in isolated rat kidney. Am J Physiol 246: F447‐F456, 1984.
 77. Campbell DJ. Circulating and tissue angiotensin systems. J Clin Invest 79: 1‐6, 1987.
 78. Campbell DJ. Tissue renin‐angiotensin system: Sites of angiotensin formation. J Cardiovasc Pharmacol 10 (Suppl 7): S1‐S8, 1987.
 79. Candido R, Burrell LM, Jandeleit K, Cooper ME. Vasoactive peptides and the kidney. In: Brenner BM, editor. Brenner: Brenner and Rector's The Kidney. St. Louis: Saunders, 2007.
 80. Capuano P, Bacic D, Roos M, Gisler SM, Stange G, Biber J, Kaissling B, Weinman EJ, Shenolikar S, Wagner CA, Murer H. Defective coupling of apical PTH receptors to phospholipase C prevents internalization of the Na+‐phosphate cotransporter NaPi‐IIa in Nherf1‐deficient mice. Am J Physiol Cell Physiol 292: C927‐C934, 2007.
 81. Carey RM. Theodore Cooper Lecture: Renal dopamine system: Paracrine regulator of sodium homeostasis and blood pressure. Hypertension 38: 297‐302, 2001.
 82. Carey RM, Wang ZQ, Siragy HM. Novel actions of angiotensin II via its renal type‐2 (AT(2)) receptor. Curr Hypertens Rep 1: 151‐157, 1999.
 83. Carriere S, Desrosiers M, Friborg J, Brunette MG. The effect of furosemide on the intrarenal blood flow distribution in the dog. Can J Physiol Pharmacol 50: 774‐783, 1972.
 84. Casellas D, Navar LG. In vitro perfusion of juxtamedullary nephrons in rats. Am J Physiol 246: F349‐F358, 1984.
 85. Chai SY, Sexton PM, Allen AM, Figdor R, Mendelsohn FA. In vitro autoradiographic localization of ANP receptors in rat kidney and adrenal gland. Am J Physiol 250: F753‐F757, 1986.
 86. Chai SY, Zhuo J, Mendelsohn FA. Localization of components of the renin‐angiotensin system and site of action of inhibitors. Arzneimittelforschung 43: 214‐221, 1993.
 87. Chan YL, Wang T. The role of protein kinase C in mediating the stimulatory effect of angiotensin II on renal tubular transport. Contrib Nephrol 95: 216‐221, 1991.
 88. Chappell MC. Emerging evidence for a functional angiotensin‐converting enzyme 2‐angiotensin‐(1‐7)‐MAS receptor axis: More than regulation of blood pressure? Hypertension 50: 596‐599, 2007.
 89. Chen C, Beach RE, Lokhandwala MF. Dopamine fails to inhibit renal tubular sodium pump in hypertensive rats. Hypertension 21: 364‐372, 1993.
 90. Chen JK, Zimpelmann J, Harris RC, Burns KD. Angiotensin IV induces tyrosine phosphorylation of focal adhesion kinase and paxillin in proximal tubule cells. Am J Physiol Renal Physiol 280: F980‐F988, 2001.
 91. Chen M, Todd‐Turla K, Wang WH, Cao X, Smart A, Brosius FC, Killen PD, Keiser JA, Briggs JP, Schnermann J. Endothelin‐1 mRNA in glomerular and epithelial cells of kidney. Am J Physiol 265: F542‐F550, 1993.
 92. Chobanian MC, Julin CM. Angiotensin II stimulates ammoniagenesis in canine renal proximal tubule segments. Am J Physiol 260: F19‐F26, 1991.
 93. Chou CL, Marsh DJ. Role of proximal convoluted tubule in pressure diuresis in the rat. Am J Physiol 251: F283‐F289, 1986.
 94. Chu TS, Peng Y, Cano A, Yanagisawa M, Alpern RJ. Endothelin(B) receptor activates NHE‐3 by a Ca2+‐dependent pathway in OKP cells. J Clin Invest 97: 1454‐1462, 1996.
 95. Cinelli AR, Efendiev R, Pedemonte CH. Trafficking of Na‐K‐ATPase and dopamine receptor molecules induced by changes in intracellular sodium concentration of renal epithelial cells. Am J Physiol Renal Physiol 295: F1117‐F1125, 2008.
 96. Clapp WL, Bowman P, Shaw GS, Patel P, Kone BC. Segmental localization of mRNAs encoding Na+‐K+‐ATPase alpha‐ and beta‐subunit isoforms in rat kidney using RT‐PCR. Kidney Int 46: 627‐638, 1994.
 97. Clausen T, Persson AE. Jens Christian Skou awarded the Nobel prize in chemistry for the identification of the Na+, K+‐pump. Acta Physiol Scand 163: 1‐2, 1998.
 98. Cogan MG. Atrial natriuretic factor can increase renal solute excretion primarily by raising glomerular filtration. Am J Physiol 250: F710‐F714, 1986.
 99. Cogan MG. Angiotensin II: A powerful controller of sodium transport in the early proximal tubule. Hypertension 15: 451‐458, 1990.
 100. Counillon L, Scholz W, Lang HJ, Pouyssegur J. Pharmacological characterization of stably transfected Na+/H+ antiporter isoforms using amiloride analogs and a new inhibitor exhibiting anti‐ischemic properties. Mol Pharmacol 44: 1041‐1045, 1993.
 101. Crowley SD, Gurley SB, Oliverio MI, Pazmino AK, Griffiths R, Flannery PJ, Spurney RF, Kim HS, Smithies O, Le TH, Coffman TM. Distinct roles for the kidney and systemic tissues in blood pressure regulation by the renin‐angiotensin system. J Clin Invest 115: 1092‐1099, 2005.
 102. Curran PF, Macintosh JR. A model system for biological water transport. Nature 193: 347‐348, 1962.
 103. D'Souza S, Garcia‐Cabado A, Yu F, Teter K, Lukacs G, Skorecki K, Moore HP, Orlowski J, Grinstein S. The epithelial sodium‐hydrogen antiporter Na+/H+ exchanger 3 accumulates and is functional in recycling endosomes. J Biol Chem 273: 2035‐2043, 1998.
 104. Danser AH, van Kats JP, Verdouw PD, Schalekamp MA. Evidence for the existence of a functional cardiac renin‐angiotensin system in humans. Circulation 96: 3795‐3796, 1997.
 105. de Bold AJ. Atrial natriuretic factor: A hormone produced by the heart. Science 230: 767‐770, 1985.
 106. de Bold AJ. Thirty years of research on atrial natriuretic factor: Historical background and emerging concepts. Can J Physiol Pharmacol 89 (8): 527‐31 2011.
 107. de Bold AJ, Borenstein HB, Veress AT, Sonnenberg H. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci 28: 89‐94, 1981.
 108. De Wardener HE, Mills IH, Clapham WF, Hayter CJ. Studies on the efferent mechanism of the sodium diuresis which follows the administration of intravenous saline in the dog. Clin Sci 21: 249‐258, 1961.
 109. Dean R, Zhuo JL, Alcorn D, Casley D, Mendelsohn FA. Cellular distribution of 125I‐endothelin‐1 binding in rat kidney following in vivo labeling. Am J Physiol 267: F845‐F852, 1994.
 110. Dean R, Zhuo JL, Alcorn D, Casley D, Mendelsohn FA. Cellular localization of endothelin receptor subtypes in the rat kidney following in vitro labelling. Clin Exp Pharmacol Physiol 23: 524‐531, 1996.
 111. Desir GV. Regulation of blood pressure and cardiovascular function by renalase. Kidney Int 76: 366‐370, 2009.
 112. Desir GV. Role of renalase in the regulation of blood pressure and the renal dopamine system. Curr Opin Nephrol Hypertens 20: 31‐36, 2011.
 113. Diamond JM, Bossert WH. Standing‐gradient osmotic flow. A mechanism for coupling of water and solute transport in epithelia. J Gen Physiol 50: 2061‐2083, 1967.
 114. Dirks JH, Cirksena WJ, Berliner RW. The effects of saline infusion on sodium reabsorption by the proximal tubule of the dog. J Clin Invest 44: 1160‐1170, 1965.
 115. Dlouha H, Bibr B, Jezek J, Zicha J. Single nephron glomerular filtration rate ratios of superficial, intercortical and juxtamedullary nephrons in rats during development. Pflugers Arch 366: 277‐279, 1976.
 116. Dominguez JH, Juhaszova M, Kleiboeker SB, Hale CC, Feister HA. Na+‐Ca2+ exchanger of rat proximal tubule: Gene expression and subcellular localization. Am J Physiol 263: F945‐F950, 1992.
 117. Dominguez JH, Rothrock JK, Macias WL, Price J. Na+ electrochemical gradient and Na+‐Ca2+ exchange in rat proximal tubule. Am J Physiol 257: F531‐F538, 1989.
 118. Donowitz M, Li X. Regulatory binding partners and complexes of NHE3. Physiol Rev 87: 825‐872, 2007.
 119. Dostanic‐Larson I, Lorenz JN, Van Huysse JW, Neumann JC, Moseley AE, Lingrel JB. Physiological role of the alpha1‐ and alpha2‐isoforms of the Na+‐K+‐ATPase and biological significance of their cardiac glycoside binding site. Am J Physiol Regul Integr Comp Physiol 290: R524‐R528, 2006.
 120. Douglas JG, Hopfer U. Novel aspect of angiotensin receptors and signal transduction in the kidney. Annu Rev Physiol 56: 649‐669, 1994.
 121.Drago J, Gerfen CR, Lachowicz JE, Steiner H, Hollon TR, Love PE, Ooi GT, Grinberg A, Lee EJ, Huang SP. Altered striatal function in a mutant mouse lacking D1A dopamine receptors. Proc Natl Acad Sci U S A 91: 12564‐12568, 1994.
 122. Du Z, Ferguson W, Wang T. Role of PKC and calcium in modulation of effects of angiotensin II on sodium transport in proximal tubule. Am J Physiol Renal Physiol 284: F688‐F692, 2003.
 123. Du Z, Wan L, Yan Q, Weinbaum S, Weinstein AM, Wang T. Regulation of glomerulotubular balance II: Impact of angiotensin II on flow‐dependent transport. Am J Physiol Renal Physiol 2012.
 124. Du Z, Yan Q, Wan L, Weinbaum S, Weinstein AM, Wang T. Regulation of glomerulotubular balance. I. Impact of dopamine on flow‐dependent transport. Am J Physiol Renal Physiol 303: F386‐F395, 2012.
 125. Dulin NO, Sorokin A, Reed E, Elliott S, Kehrl JH, Dunn MJ. RGS3 inhibits G protein‐mediated signaling via translocation to the membrane and binding to Galpha11. Mol Cell Biol 19: 714‐723, 1999.
 126. Efendiev R, Budu CE, Cinelli AR, Bertorello AM, Pedemonte CH. Intracellular Na+ regulates dopamine and angiotensin II receptors availability at the plasma membrane and their cellular responses in renal epithelia. J Biol Chem 278: 28719‐28726, 2003.
 127. Eiam‐Ong S, Hilden SA, King AJ, Johns CA, Madias NE. Endothelin‐1 stimulates the Na+/H+ and Na+/HCO3− transporters in rabbit renal cortex. Kidney Int 42: 18‐24, 1992.
 128. Elshourbagy NA, Lee JA, Korman DR, Nuthalaganti P, Sylvester DR, Dilella AG, Sutiphong JA, Kumar CS. Molecular cloning and characterization of the major endothelin receptor subtype in porcine cerebellum. Mol Pharmacol 41: 465‐473, 1992.
 129. Ernst SA. Transport ATPase cytochemistry: Ultrastructural localization of potassium‐dependent and potassium‐independent phosphatase activities in rat kidney cortex. J Cell Biol 66: 586‐608, 1975.
 130. Esther CR, Marino EM, Howard TE, Machaud A, Corvol P, Capecchi MR, Bernstein KE. The critical role of tissue angiotensin‐converting enzyme as revealed by gene targeting in mice. J Clin Invest 99: 2375‐2385, 1997.
 131. Eysenhardt CW. De structura renum observationes microscopiac. Berolinensis: 1818.
 132. Feraille E, Doucet A. Sodium‐potassium‐adenosinetriphosphatase‐dependent sodium transport in the kidney: Hormonal control. Physiol Rev 81: 345‐418, 2001.
 133. Ferrandi M, Salardi S, Tripodi G, Barassi P, Rivera R, Manunta P, Goldshleger R, Ferrari P, Bianchi G, Karlish SJ. Evidence for an interaction between adducin and Na(+)‐K(+)‐ATPase: Relation to genetic hypertension. Am J Physiol 277: H1338‐H1349, 1999.
 134. Ferrario CM, Chappell MC, Tallant EA, Brosnihan KB, Diz DI. Counterregulatory actions of angiotensin‐(1‐7). Hypertension 30: 535‐541, 1997.
 135. Fetterman GH, Shuplock NA, Philipp FJ, Gregg HS. The growth and maturation of human glomeruli and proximal convolutions from term to adulthood: Studies by microdissection. Pediatrics 35: 601‐619, 1965.
 136. Finco DR, Duncan JR. Relationship of glomerular number and diameter to body size of the dog. Am J Vet Res 33: 2447‐2450, 1972.
 137. Fitzgibbon W, Morgan T. Effect of atrial natriuretic peptide on collecting duct function evaluated by stop‐flow in rabbits. Clin Exp Pharmacol Physiol 14: 169‐174, 1987.
 138. Fitzgibbon W, Morgan T. Effect of atrial peptide on collecting duct function. Clin Exp Pharmacol Physiol 15: 845‐855, 1988.
 139. Fitzgibbons JP, Gennari FJ, Garfinkel HB, Cortell S. Dependence of saline‐induced natriuresis upon exposure of the kidney to the physical effects of extracellular fluid volume expansion. J Clin Invest 54: 1428‐1436, 1974.
 140. Friedman PA. Codependence of renal calcium and sodium transport. Annu Rev Physiol 60: 179‐197, 1998.
 141. Friedman PA, Figueiredo JF, Maack T, Windhager EE. Sodium‐calcium interactions in the renal proximal convoluted tubule of the rabbit. Am J Physiol 240: F558‐F568, 1981.
 142. Frindt G, Lee CO, Yang JM, Windhager EE. Potential role of cytoplasmic calcium ions in the regulation of sodium transport in renal tubules. Miner Electrolyte Metab 14: 40‐47, 1988.
 143. Fromter E. The Feldberg Lecture 1976. Solute transport across epithelia: What can we learn from micropuncture studies in kidney tubules? J Physiol 288: 1‐31, 1979.
 144. Fulladosa X, Moreso F, Narvaez JA, Grinyo JM, Seron D. Estimation of total glomerular number in stable renal transplants. J Am Soc Nephrol 14: 2662‐2668, 2003.
 145. Fuster DG, Bobulescu IA, Zhang J, Wade J, Moe OW. Characterization of the regulation of renal Na+/H+ exchanger NHE3 by insulin. Am J Physiol Renal Physiol 292: F577‐F585, 2007.
 146. Garcia NH, Garvin JL. Angiotensin 1‐7 has a biphasic effect on fluid absorption in the proximal straight tubule. J Am Soc Nephrol 5: 1133‐1138, 1994.
 147. Garcia NH, Garvin JL. Endothelin's biphasic effect on fluid absorption in the proximal straight tubule and its inhibitory cascade. J Clin Invest 93: 2572‐2577, 1994.
 148. Garcia R, Cantin M, Thibault G, Ong H, Genest J. Relationship of specific granules to the natriuretic and diuretic activity of rat atria. Experientia 38: 1071‐1073, 1982.
 149. Garg LC, Knepper MA, Burg MB. Mineralocorticoid effects on Na‐K‐ATPase in individual nephron segments. Am J Physiol 240: F536‐F544, 1981.
 150. Garvin J, Sanders K. Endothelin inhibits fluid and bicarbonate transport in part by reducing Na+/K+ ATPase activity in the rat proximal straight tubule. J Am Soc Nephrol 2: 976‐982, 1991.
 151. Garvin JL. Inhibition of Jv by ANF in rat proximal straight tubules requires angiotensin. Am J Physiol 257: F907‐F911, 1989.
 152. Garvin JL. Angiotensin stimulates bicarbonate transport and Na+/K+ ATPase in rat proximal straight tubules. J Am Soc Nephrol 1: 1146‐1152, 1991.
 153. Geibel J, Giebisch G, Boron WF. Angiotensin II stimulates both Na(+)‐H+ exchange and Na+/HCO3− cotransport in the rabbit proximal tubule. Proc Natl Acad Sci U S A 87: 7917‐7920, 1990.
 154. Gennari FJ, Maddox DA. Renal regulation of acid‐base homeostasis: Integrative response. In: Seldin DW, Giebisch G, editors. The Kidney: Physiology and Pathophysiology. New York: Raven Press, 1992.
 155. Gerich JE. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: Therapeutic implications. Diabet Med 27: 136‐142, 2010.
 156. Gertz KH, Boylan JW. Glomerulo‐tubular balance. In: Orloff J, Berliner RW, editors. Handbook of Physiology. Bethesda: American Physiological Society, 1973.
 157. Gertz KH, Mangos JA, Braun G, Pagel HD. On the glomerular tubular balance in the rat kidney. Pflugers Arch Gesamte Physiol Menschen Tiere 285: 360‐372, 1965.
 158. Giebisch G. Measurements of electrical potential differences on single nephrons of the perfused Necturus kidney. J Gen Physiol 44: 659‐678, 1961.
 159. Giebisch G, KLOSE RM, Windhager EE. Micorpuncture study of hypertonic sodium chloride loading in the rat. Am J Physiol 206: 687‐693, 1964.
 160. Giebisch G, Windhager EE. Renal tubular transfer of sodium, chloride and potassium. Am J Med 36: 643‐669, 1964.
 161. Gildea JJ, Israel JA, Johnson AK, Zhang J, Jose PA, Felder RA. Caveolin‐1 and dopamine‐mediated internalization of NaKATPase in human renal proximal tubule cells. Hypertension 54: 1070‐1076, 2009.
 162. Gildea JJ, Wang X, Shah N, Tran H, Spinosa M, Van SR, Sasaki M, Yatabe J, Carey RM, Jose PA, Felder RA. Dopamine and angiotensin type 2 receptors cooperatively inhibit sodium transport in human renal proximal tubule cells. Hypertension 60(2):396‐403, 2012.
 163. Glabman S, Aynedjian HS, Bank N. Micropuncture study of the effect of acute reductions in glomerular filtration rate on sodium and water reabsorption by the proximal tubules of the rat. J Clin Invest 44: 1410‐1416, 1965.
 164. Gmaj P, Murer H, Kinne R. Calcium ion transport across plasma membranes isolated from rat kidney cortex. Biochem J 178: 549‐557, 1979.
 165. Goetz KL. Atrial natriuretic peptide and atrial pressure. N Engl J Med 316: 485‐486, 1987.
 166. Goldman ID, Fyfe JM, Bowen D, Loftfield S, Schafer JA. The effect of microtubular inhibitors on transport of alpha‐aminoisobutyric acid. Inhibition of uphill transport without changes in transmembrane gradients of Na+, K+, or H+. Biochim Biophys Acta 467: 185‐191, 1977.
 167. Gottschalk CW, Lassiter WE. Micropuncture methodology. In: Orloff J, Berliner RW, editors. Handbook of Physiology. Washington, D.C.: American Physiological Society, 1973.
 168. Gottschalk CW, Mylle M. Micropuncture study of the mammalian urinary concentrating mechanism: Evidence for the countercurrent hypothesis. Am J Physiol 196: 927‐936, 1959.
 169. Goyal S, Mentone S, Aronson PS. Immunolocalization of NHE8 in rat kidney. Am J Physiol Renal Physiol 288: F530‐F538, 2005.
 170. Goyal S, Vanden Heuvel G, Aronson PS. Renal expression of novel Na+/H+ exchanger isoform NHE8. Am J Physiol Renal Physiol 284: F467‐F473, 2003.
 171. Granger JP, Haas JA, Pawlowska D, Knox FG. Effect of direct increases in renal interstitial hydrostatic pressure on sodium excretion. Am J Physiol 254: F527‐F532, 1988.
 172. Green R, Giebisch G. Luminal hypotonicity: A driving force for fluid absorption from the proximal tubule. Am J Physiol 246: F167‐F174, 1984.
 173. Green R, Giebisch G. Osmotic forces driving water reabsorption in the proximal tubule of the rat kidney. Am J Physiol 257: F669‐F675, 1989.
 174. Green R, Moriarty RJ, Giebisch G. Ionic requirements of proximal tubular fluid reabsorption flow dependence of fluid transport. Kidney Int 20: 580‐587, 1981.
 175. Guder WG. Stimulation of renal gluconeogenesis by angiotensin II. Biochim Biophys Acta 584: 507‐519, 1979.
 176. Guntupalli J, DuBose TD Jr., Effects of endothelin on rat renal proximal tubule Na+‐Pi cotransport and Na+/H+ exchange. Am J Physiol 266: F658‐F666, 1994.
 177. Gurley SB, Riquier‐Brison AD, Schnermann J, Sparks MA, Allen AM, Haase VH, Snouwaert JN, Le TH, McDonough AA, Koller BH, Coffman TM. AT1A angiotensin receptors in the renal proximal tubule regulate blood pressure. Cell Metab 13: 469‐475, 2011.
 178. Guyton AC, Hall JE. Textbook of Medical Physiology. Philadelphia: Saunders, Elsevier, 2011, pp. 305‐306.
 179. Guyton AC, Hall JE, Coleman TG, Manning RD, Jr., Norman RAJ. The dominant role of the kidneys in long‐term arterial pressure regulation in normal and hypertensive states. In: Laragh JH, Brenner BM, editors. Hypertension: Pathophysiology, Diagnosis, and Management. New York: Raven Press, 1995.
 180. Gwathmey TM, Pendergrass KD, Reid SD, Rose JC, Diz DI, Chappell MC. Angiotensin‐(1‐7)‐angiotensin‐converting enzyme 2 attenuates reactive oxygen species formation to angiotensin II within the cell nucleus. Hypertension 55: 166‐171, 2010.
 181. Gyory AZ, Kinne R. Energy source for transepithelial sodium transport in rat renal proximal tubules. Pflugers Arch 327: 234‐260, 1971.
 182. Haas JA, Granger JP, Knox FG. Effect of renal perfusion pressure on sodium reabsorption from proximal tubules of superficial and deep nephrons. Am J Physiol 250: F425‐F429, 1986.
 183. Haberle D. Significance of humoral factors in the tubulus fluid for maintenance of glomerulo‐tubular balance in the proximal tubulus of the rat kidney. Fortschr Med 96: 2337, 1978.
 184. Haberle DA, von BH. Characteristics of glomerulotubular balance. Am J Physiol 244: F355‐F366, 1983.
 185. Hakam AC, Hussain T. Angiotensin II type 2 receptor agonist directly inhibits proximal tubule sodium pump activity in obese but not in lean Zucker rats. Hypertension 47: 1117‐1124, 2006.
 186. Hall JE. Regulation of glomerular filtration rate and sodium excretion by angiotensin II. Fed Proc 45: 1431‐1437, 1986.
 187. Hall JE, Brands MW, Shek EW. Central role of the kidney and abnormal fluid volume control in hypertension. J Hum Hypertens 10: 633‐639, 1996.
 188. Hammond TG, Yusufi AN, Knox FG, Dousa TP. Administration of atrial natriuretic factor inhibits sodium‐coupled transport in proximal tubules. J Clin Invest 75: 1983‐1989, 1985.
 189. Handa RK. Characterization and signaling of the AT(4) receptor in human proximal tubule epithelial (HK‐2) cells. J Am Soc Nephrol 12: 440‐449, 2001.
 190. Handa RK, Krebs LT, Harding JW, Handa SE. Angiotensin IV AT4‐receptor system in the rat kidney. Am J Physiol 274: F290‐F299, 1998.
 191. Hansell P, Fasching A. The effect of dopamine receptor blockade on natriuresis is dependent on the degree of hypervolemia. Kidney Int 39: 253‐258, 1991.
 192. Harris PJ. Regulation of proximal tubule function by angiotensin. Clin Exp Pharmacol Physiol 19: 213‐222, 1992.
 193. Harris PJ, Navar LG. Tubular transport responses to angiotensin II. Am J Physiol Renal Physiol 248: F621‐F630, 1985.
 194. Harris PJ, Navar LG, Ploth DW. Evidence for angiotensin‐stimulated proximal tubular fluid reabsorption in normotensive and hypertensive rats: Effect of acute administration of captopril. Clin Sci (Lond) 66: 541‐544, 1984.
 195. Harris PJ, Skinner SL. Intra‐renal interactions between angiotensin II and atrial natriuretic factor. Kidney Int Suppl 30: S87‐S91, 1990.
 196. Harris PJ, Skinner SL, Zhuo JL. The effects of atrial natriuretic peptide and glucagon on proximal glomerulo‐tubular balance in anaesthetized rats. J Physiol 402: 29‐42, 1988.
 197. Harris PJ, Skinner SL, Zhuo JL. Haemodynamic and renal tubular responses to low‐dose infusion or bolus injection of the peptide ANF in anaesthetized rats. J Physiol 412: 309‐320, 1989.
 198. Harris PJ, Thomas D, Morgan TO. Atrial natriuretic peptide inhibits angiotensin‐stimulated proximal tubular sodium and water reabsorption. Nature 326: 697‐698, 1987.
 199. Harris PJ, Thomas D, Zhuo JL, Skinner SL. Regulation of proximal tubule sodium reabsorption by angiotensin II (AII) and atrial natriuretic factor (ANF). Acta Physiol Scand Suppl 591: 63‐65, 1990.
 200. Harris PJ, Young JA. Dose‐dependent stimulation and inhibition of proximal tubular sodium reabsorption by angiotensin II in the rat kidney. Pflugers Arch 367: 295‐297, 1977.
 201. Harris PJ, Zhuo JL, Mendelsohn FA, Skinner SL. Haemodynamic and renal tubular effects of low doses of endothelin in anaesthetized rats. J Physiol 433: 25‐39, 1991.
 202. Harris PJ, Zhuo JL, Skinner SL. Effects of angiotensins II and III on glomerulotubular balance in rats. Clin Exp Pharmacol Physiol 14: 489‐502, 1987.
 203. Harrison‐Bernard LM, Cook AK, Oliverio MI, Coffman TM. Renal segmental microvascular responses to ANG II in AT1A receptor null mice. Am J Physiol Renal Physiol 284: F538‐F545, 2003.
 204. Harrison‐Bernard LM, Monjure CJ, Bivona BJ. Efferent arterioles exclusively express the subtype 1A angiotensin receptor: Functional insights from genetic mouse models. Am J Physiol Renal Physiol 290: F1177‐F1186, 2006.
 205. Harrison‐Bernard LM, Zhuo J, Kobori H, Ohishi M, Navar LG. Intrarenal AT(1) receptor and ACE binding in ANG II‐induced hypertensive rats. Am J Physiol Renal Physiol 282: F19‐F25, 2002.
 206. Hashimoto S, Adams JW, Bernstein KE, Schnermann J. Micropuncture determination of nephron function in mice without tissue angiotensin‐converting enzyme. Am J Physiol Renal Physiol 288: F445‐F452, 2005.
 207. Haug C, Grill C, Schmid‐Kotsas A, Gruenert A, Jehle PM. Endothelin release by rabbit proximal tubule cells: Modulatory effects of cyclosporine A, tacrolimus, HGF and EGF. Kidney Int 54: 1626‐1636, 1998.
 208. Haynes WG, Webb DJ. Endothelin as a regulator of cardiovascular function in health and disease. J Hypertens 16: 1081‐1098, 1998.
 209. Hayslett JP, Kashgarian M. A micropuncture study of the renal handling of lithium. Pflugers Arch 380: 159‐163, 1979.
 210. He P, Klein J, Yun CC. Activation of Na+/H+ exchanger NHE3 by angiotensin II is mediated by inositol 1,4,5‐triphosphate (IP3) receptor‐binding protein released with IP3 (IRBIT) and Ca2+/calmodulin‐dependent protein kinase II. J Biol Chem 285: 27869‐27878, 2010.
 211. Hediger MA, Rhoads DB. Molecular physiology of sodium‐glucose cotransporters. Physiol Rev 74: 993‐1026, 1994.
 212. Heilmann M, Neudecker S, Wolf I, Gubhaju L, Sticht C, Schock‐Kusch D, Kriz W, Bertram JF, Schad LR, Gretz N. Quantification of glomerular number and size distribution in normal rat kidneys using magnetic resonance imaging. Nephrol Dial Transplant 27 (1): 100‐7, 2011.
 213. Hilden S, Sacktor B. Potential‐dependent D‐glucose uptake by renal brush border membrane vesicles in the absence of sodium. Am J Physiol 242: F340‐F345, 1982.
 214. Holzgreve H, Schrier RW, Eigler J. Renal regulation of the sodium balance. Internist (Berl) 12: 69‐76, 1971.
 215. Honegger KJ, Capuano P, Winter C, Bacic D, Stange G, Wagner CA, Biber J, Murer H, Hernando N. Regulation of sodium‐proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC). Proc Natl Acad Sci U S A 103: 803‐808, 2006.
 216. Hopfer U. Unraveling the complex mechanosensory machine of solitary cilia. Editorial Focus for Ms f657‐2009. Am J Physiol Renal Physiol 298 (5): F1095, 2010.
 217. Horita S, Zheng Y, Hara C, Yamada H, Kunimi M, Taniguchi S, Uwatoko S, Sugaya T, Goto A, Fujita T, Seki G. Biphasic regulation of Na+‐HCO3− cotransporter by angiotensin II type 1A receptor. Hypertension 40: 707‐712, 2002.
 218. Horster M, Burg M, Potts D, Orloff J. Fluid absorption by proximal tubules in the absence of a colloid osmotic gradient. Kidney Int 4: 6‐11, 1973.
 219. Horster M, Kemler BJ, Valtin H. Intracortical distribution of number and volume of glomeruli during postnatal maturation in the dog. J Clin Invest 50: 796‐800, 1971.
 220. Horster M, Nagel W, Schnermann J, Thurau K. On the problem of direct angiotensin effect on the resorption of sodium in the proximal tubule and Henle's loop of the rat kidney. Pflugers Arch Gesamte Physiol Menschen Tiere 292: 118‐128, 1966.
 221. Horster M, Thurau K. Micropuncture studies on the filtration rate of single superficial and juxtamedullary glomeruli in the rat kidney. Pflugers Arch Gesamte Physiol Menschen Tiere 301: 162‐181, 1968.
 222. Hosoda K, Nakao K, Hiroshi A, Suga S, Ogawa Y, Mukoyama M, Shirakami G, Saito Y, Nakanishi S, Imura H. Cloning and expression of human endothelin‐1 receptor cDNA. FEBS Lett 287: 23‐26, 1991.
 223. Houillier P, Chambrey R, Achard JM, Froissart M, Poggioli J, Paillard M. Signaling pathways in the biphasic effect of angiotensin II on apical Na/H antiport activity in proximal tubule. Kidney Int 50: 1496‐1505, 1996.
 224. Hoy WE, Bertram JF, Denton RD, Zimanyi M, Samuel T, Hughson MD. Nephron number, glomerular volume, renal disease and hypertension. Curr Opin Nephrol Hypertens 17: 258‐265, 2008.
 225. Hoy WE, Hughson MD, Diouf B, Zimanyi M, Samuel T, McNamara BJ, Douglas‐Denton RN, Holden L, Mott SA, Bertram JF. Distribution of volumes of individual glomeruli in kidneys at autopsy: Association with physical and clinical characteristics and with ethnic group. Am J Nephrol 33 (Suppl 1): 15‐20, 2011.
 226. Hoy WE, Hughson MD, Singh GR, Douglas‐Denton R, Bertram JF. Reduced nephron number and glomerulomegaly in Australian Aborigines: A group at high risk for renal disease and hypertension. Kidney Int 70: 104‐110, 2006.
 227. Hu MC, Fan L, Crowder LA, Karim‐Jimenez Z, Murer H, Moe OW. Dopamine acutely stimulates Na+/H+ exchanger (NHE3) endocytosis via clathrin‐coated vesicles: Dependence on protein kinase A‐mediated NHE3 phosphorylation. J Biol Chem 276: 26906‐26915, 2001.
 228. Huang CL, Lewicki J, Johnson LK, Cogan MG. Renal mechanism of action of rat atrial natriuretic factor. J Clin Invest 75: 769‐773, 1985.
 229. Hughes JM, Ragsdale NV, Felder RA, Chevalier RL, King B, Carey RM. Diuresis and natriuresis during continuous dopamine‐1 receptor stimulation. Hypertension 11: I69‐I74, 1988.
 230. Hughson M, Farris AB, III, Douglas‐Denton R, Hoy WE, Bertram JF. Glomerular number and size in autopsy kidneys: The relationship to birth weight. Kidney Int 63: 2113‐2122, 2003.
 231. Hughson MD, Gobe GC, Hoy WE, Manning RD, Jr., Douglas‐Denton R, Bertram JF. Associations of glomerular number and birth weight with clinicopathological features of African Americans and whites. Am J Kidney Dis 52: 18‐28, 2008.
 232. Hussain T, Lokhandwala MF. Renal dopamine receptor function in hypertension. Hypertension 32: 187‐197, 1998.
 233. Ichikawa I, Brenner BM. Importance of efferent arteriolar vascular tone in regulation of proximal tubule fluid reabsorption and glomerulotubular balance in the rat. J Clin Invest 65: 1192‐1201, 1980.
 234. Ichikawa I, Hoyer JR, Seiler MW, Brenner BM. Mechanism of glomerulotubular balance in the setting of heterogeneous glomerular injury. Preservation of a close functional linkage between individual nephrons and surrounding microvasculature. J Clin Invest 69: 185‐198, 1982.
 235. Ikeda K, Onimaru H, Yamada J, Inoue K, Ueno S, Onaka T, Toyoda H, Arata A, Ishikawa TO, Taketo MM, Fukuda A, Kawakami K. Malfunction of respiratory‐related neuronal activity in Na+, K+‐ATPase alpha2 subunit‐deficient mice is attributable to abnormal Cl‐ homeostasis in brainstem neurons. J Neurosci 24: 10693‐10701, 2004.
 236. Imig JD, Cook AK, Inscho EW. Postglomerular vasoconstriction to angiotensin II and norepinephrine depends on intracellular calcium release. Gen Pharmacol 34: 409‐415, 2000.
 237. Imig JD, Zhao X, Falck JR, Wei S, Capdevila JH. Enhanced renal microvascular reactivity to angiotensin II in hypertension is ameliorated by the sulfonimide analog of 11,12‐ epoxyeicosatrienoic acid. J Hypertens 19: 983‐992, 2001.
 238. Ingelfinger JR, Jung F, Diamant D, Haveran L, Lee E, Brem A, Tang SS. Rat proximal tubule cell line transformed with origin‐defective SV40 DNA: Autocrine ANG II feedback. Am J Physiol 276: F218‐F227, 1999.
 239. Inscho EW, Carmines PK, Cook AK, Navar LG. Afferent arteriolar responsiveness to altered perfusion pressure in renal hypertension. Hypertension 15: 748‐752, 1990.
 240. Inscho EW, Imig JD, Deichmann PC, Cook AK. Candesartan cilexetil protects against loss of autoregulatory efficiency in angiotensin II‐infused rats. J Am Soc Nephrol 10 (Suppl 11): S178‐S183, 1999.
 241. Itabashi A, Chan L, Shapiro JI, Cheung C, Schrier RW. Comparison of the natriuretic response to atriopeptin III and loop diuretic in the isolated perfused rat kidney. Clin Sci (Lond) 73: 143‐150, 1987.
 242. Iwamoto T, Kita S. Hypertension, Na+/Ca2+ exchanger, and Na+, K+‐ATPase. Kidney Int 69: 2148‐2154, 2006.
 243. Jacobson HR. Characteristics of volume reabsorption in rabbit superficial and juxtamedullary proximal convoluted tubules. J Clin Invest 63: 410‐418, 1979.
 244. Jacobson HR. Effects of CO2 and acetazolamide on bicarbonate and fluid transport in rabbit proximal tubules. Am J Physiol 240: F54‐F62, 1981.
 245. Jacobson HR, Kokko JP. Intrinsic differences in various segments of the proximal convoluted tubule. J Clin Invest 57: 818‐825, 1976.
 246. James PF, Grupp IL, Grupp G, Woo AL, Askew GR, Croyle ML, Walsh RA, Lingrel JB. Identification of a specific role for the Na,K‐ATPase alpha 2 isoform as a regulator of calcium in the heart. Mol Cell 3: 555‐563, 1999.
 247. Jamison RL. Micropuncture study of superficial and juxtamedullary nephrons in the rat. Am J Physiol 218: 46‐55, 1970.
 248. Jamison RL. Intrarenal heterogeneity. The case for two functionally dissimilar populations of nephrons in the mammalian kidney. Am J Med 54: 281‐289, 1973.
 249. Johnston CI, Fabris B, Jandeleit K. Intrarenal renin‐angiotensin system in renal physiology and pathophysiology. Kidney Int Suppl 42: S59‐S63, 1993.
 250. Jorgensen PL. Isolation and characterization of the components of the sodium pump. Q Rev Biophys 7: 239‐274, 1974.
 251. Jorgensen PL. Sodium and potassium ion pump in kidney tubules. Physiol Rev 60: 864‐917, 1980.
 252. Jose PA, Eisner GM, Felder RA. Role of dopamine receptors in the kidney in the regulation of blood pressure. Curr Opin Nephrol Hypertens 11: 87‐92, 2002.
 253. Jose PA, Soares‐da‐Silva P, Eisner GM, Felder RA. Dopamine and G protein‐coupled receptor kinase 4 in the kidney: Role in blood pressure regulation. Biochim Biophys Acta 1802: 1259‐1267, 2010.
 254. Jourdain M, Amiel C, Friedlander G. Modulation of Na‐H exchange activity by angiotensin II in opossum kidney cells. Am J Physiol 263: C1141‐C1146, 1992.
 255. Jung JS, Bhat RV, Preston GM, Guggino WB, Baraban JM, Agre P. Molecular characterization of an aquaporin cDNA from brain: Candidate osmoreceptor and regulator of water balance. Proc Natl Acad Sci U S A 91: 13052‐13056, 1994.
 256. Kaelin WG, Jr. Molecular biology. Use and abuse of RNAi to study mammalian gene function. Science 337: 421‐422, 2012.
 257. Kallskog O, Wolgast M. Driving forces over the peritubular capillary membrane in the rat kidney during antidiuresis and saline expansion. Acta Physiol Scand 89: 116‐125, 1973.
 258. Kanai Y, Lee WS, You G, Brown D, Hediger MA. The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D‐glucose. J Clin Invest 93: 397‐404, 1994.
 259. Kaplan JH. Biochemistry of Na,K‐ATPase. Annu Rev Biochem 71: 511‐535, 2002.
 260. Karim Z, Defontaine N, Paillard M, Poggioli J. Protein kinase C isoforms in rat kidney proximal tubule: Acute effect of angiotensin II. Am J Physiol 269: C134‐C140, 1995.
 261. Karim ZG, Chambrey R, Chalumeau C, Defontaine N, Warnock DG, Paillard M, Poggioli J. Regulation by PKC isoforms of Na(+)/H(+) exchanger in luminal membrane vesicles isolated from cortical tubules. Am J Physiol 277: F773‐F778, 1999.
 262. Kashgarian M, Biemesderfer D, Caplan M, Forbush B, III. Monoclonal antibody to Na,K‐ATPase: Immunocytochemical localization along nephron segments. Kidney Int 28: 899‐913, 1985.
 263. Katz AI, Doucet A, Morel F. Na‐K‐ATPase activity along the rabbit, rat, and mouse nephron. Am J Physiol 237: F114‐F120, 1979.
 264. Kaunisto K, Parkkila S, Rajaniemi H, Waheed A, Grubb J, Sly WS. Carbonic anhydrase XIV: Luminal expression suggests key role in renal acidification. Kidney Int 61: 2111‐2118, 2002.
 265. Kawakami K, Nojima H, Ohta T, Nagano K. Molecular cloning and sequence analysis of human Na,K‐ATPase beta‐subunit. Nucleic Acids Res 14: 2833‐2844, 1986.
 266. Kawakami K, Ohta T, Nojima H, Nagano K. Primary structure of the alpha‐subunit of human Na,K‐ATPase deduced from cDNA sequence. J Biochem 100: 389‐397, 1986.
 267. Kemp BA, Bell JF, Rottkamp DM, Howell NL, Shao W, Navar LG, Padia SH, Carey RM. Intrarenal angiotensin III is the predominant agonist for proximal tubule angiotensin type 2 receptors. Hypertension 60 (2): 387‐95, 2012.
 268. Kessler SP, Hashimoto S, Senanayake PS, Gaughan C, Sen GC, Schnermann J. Nephron function in transgenic mice with selective vascular or tubular expression of Angiotensin‐converting enzyme. J Am Soc Nephrol 16: 3535‐3542, 2005.
 269. Kiil F. Mechanism of glomerulotubular balance: The whole kidney approach. Ren Physiol 5: 209‐221, 1982.
 270. Kirchner KA. Lithium as a marker for proximal tubular delivery during low salt intake and diuretic infusion. Am J Physiol 253: F188‐F196, 1987.
 271. Kitamura K, Shiraishi N, Singer WD, Handlogten ME, Tomita K, Miller RT. Endothelin‐B receptors activate Galpha13. Am J Physiol 276: C930‐C937, 1999.
 272. Kittelson JA. The postnatal growth of the kidney of the albino rat, with observations on an adult human kidney. Anat Rec 13: 385‐408, 1917.
 273. Knox FG, Cuche J‐L, Ott CE, Diaz‐Buxo JA, Marchand G. Regulation of glomerular filtration and proximal tubule reabsorption. Circ Res 36: 107‐118, 1975.
 274. Kobori H, Harrison‐Bernard LM, Navar LG. Enhancement of angiotensinogen expression in angiotensin II‐dependent hypertension. Hypertension 37: 1329‐1335, 2001.
 275. Kobori H, Nangaku M, Navar LG, Nishiyama A. The intrarenal renin‐angiotensin system: From physiology to the pathobiology of hypertension and kidney disease. Pharmacol Rev 59: 251‐287, 2007.
 276. Kohan DE. Endothelin synthesis by rabbit renal tubule cells. Am J Physiol 261: F221‐F226, 1991.
 277. Kohan DE. Endothelins: Renal tubule synthesis and actions. Clin Exp Pharmacol Physiol 23: 337‐344, 1996.
 278. Kohan DE. Endothelin, hypertension and chronic kidney disease: New insights. Curr Opin Nephrol Hypertens 19: 134‐139, 2010.
 279. Kohan DE, Rossi NF, Inscho EW, Pollock DM. Regulation of blood pressure and salt homeostasis by endothelin. Physiol Rev 91: 1‐77, 2011.
 280. Kohzuki M, Johnston CI, Abe K, Chai SY, Casley DJ, Yasujima M, Yoshinaga K, Mendelsohn FA. In vitro autoradiographic endothelin‐1 binding sites and sarafotoxin S6B binding sites in rat tissues. Clin Exp Pharmacol Physiol 18: 509‐515, 1991.
 281. Kohzuki M, Johnston CI, Chai SY, Casley DJ, Mendelsohn FA. Localization of endothelin receptors in rat kidney. Eur J Pharmacol 160: 193‐194, 1989.
 282. Kokko JP, Burg MB, Orloff J. Characteristics of NaCl and water transport in the renal proximal tubule. J Clin Invest 50: 69‐76, 1971.
 283. Kokko JP, Rector FC. Flow dependence of transtubular potential difference in isolated perfused segments of rabbit proximal convoluted tubule. J Clin Invest 50: 2745‐2750, 1971.
 284. Kolb RJ, Woost PG, Hopfer U. Membrane trafficking of angiotensin receptor type‐1 and mechanochemical signal transduction in proximal tubule cells. Hypertension 44: 352‐359, 2004.
 285. Komuro I, Wenninger KE, Philipson KD, Izumo S. Molecular cloning and characterization of the human cardiac Na+/Ca2+ exchanger cDNA. Proc Natl Acad Sci U S A 89: 4769‐4773, 1992.
 286. Kondo Y, Imai M, Kangawa K, Matsuo H. Lack of direct action of alpha‐human atrial natriuretic polypeptide on the in vitro perfused segments of Henle's loop isolated from rabbit kidney. Pflugers Arch 406: 273‐278, 1986.
 287. Koomans HA, Boer WH, Dorhout Mees EJ. Evaluation of lithium clearance as a marker of proximal tubule sodium handling. Kidney Int 36: 2‐12, 1989.
 288. Krapf R, Solioz M. Na/H antiporter mRNA expression in single nephron segments of rat kidney cortex. J Clin Invest 88: 783‐788, 1991.
 289. Kriz W, Bankir L. A standard nomenclature for structures of the kidney. The Renal Commission of the International Union of Physiological Sciences (IUPS). Kidney Int 33: 1‐7, 1988.
 290. Kriz W, Kaissling B. Structural and functional organization of the kidney. In: Alpern RJ, Hebert SC, editors. Seldin and Giebisch's The Kidney: Physiology and Pathophysiology. London: Academic Press, 2008.
 291. Laghmani K, Preisig PA, Alpern RJ. The role of endothelin in proximal tubule proton secretion and the adaptation to a chronic metabolic acidosis. J Nephrol 15 (Suppl 5): S75‐S87, 2002.
 292. Laghmani K, Preisig PA, Moe OW, Yanagisawa M, Alpern RJ. Endothelin‐1/endothelin‐B receptor‐mediated increases in NHE3 activity in chronic metabolic acidosis. J Clin Invest 107: 1563‐1569, 2001.
 293. Lameire NH, Lifschitz MD, Stein JH. Heterogeneity of nephron function. Annu Rev Physiol 39: 159‐184, 1977.
 294. Lang F. Cell volume control. In: Alpern RJ, Hebert SC, editors. The Kidney: Physiology and Pathophysiology. Burlington, San Diego, & London: Academic Press, 2008.
 295. Lang F, Messner G, Rehwald W. Electrophysiology of sodium‐coupled transport in proximal renal tubules. Am J Physiol 250: F953‐F962, 1986.
 296. Larsen EH, Mobjerg N. Na+ recirculation and isosmotic transport. J Membr Biol 212: 1‐15, 2006.
 297. Larsen EH, Willumsen NJ, Mobjerg N, Sorensen JN. The lateral intercellular space as osmotic coupling compartment in isotonic transport. Acta Physiol (Oxf) 195: 171‐186, 2009.
 298. Le TH, Oliverio MI, Kim HS, Salzler H, Dash RC, Howell DN, Smithies O, Bronson S, Coffman TM. A gammaGT‐AT1A receptor transgene protects renal cortical structure in AT1 receptor‐deficient mice. Physiol Genomics 18: 290‐298, 2004.
 299. Ledoussal C, Lorenz JN, Nieman ML, Soleimani M, Schultheis PJ, Shull GE. Renal salt wasting in mice lacking NHE3 Na+/H+ exchanger but not in mice lacking NHE2. Am J Physiol Renal Physiol 281: F718‐F727, 2001.
 300. Lee YJ, Lee YJ, Han HJ. Regulatory mechanisms of Na(+)/glucose cotransporters in renal proximal tubule cells. Kidney Int Suppl S27‐S35, 2007.
 301. Leong PK, Yang LE, Holstein‐Rathlou NH, McDonough AA. Angiotensin II clamp prevents the second step in renal apical NHE3 internalization during acute hypertension. Am J Physiol Renal Physiol 283: F1142‐F1150, 2002.
 302. Lewis SE, Erickson RP, Barnett LB, Venta PJ, Tashian RE. N‐ethyl‐N‐nitrosourea‐induced null mutation at the mouse Car‐2 locus: An animal model for human carbonic anhydrase II deficiency syndrome. Proc Natl Acad Sci U S A 85: 1962‐1966, 1988.
 303. Lewy JE, Windhager EE. Peritubular control of proximal tubular fluid reabsorption in the rat kidney. Am J Physiol 214: 943‐954, 1968.
 304. Leyssac PP. Dependence of glomerular filtration rate on proximal tubular reabsorption of salt. Acta Physiol Scand 58: 236‐242, 1963.
 305. Leyssac PP. The in vivo effect of angiotensin on the proximal tubular reabsorption of salt in rat kidneys. Acta Physiol Scand 62: 436‐448, 1964.
 306. Li H, Weatherford ET, Davis DR, Keen HL, Grobe JL, Daugherty A, Cassis LA, Allen AM, Sigmund CD. Renal proximal tubule angiotensin AT1A receptors regulate blood pressure. Am J Physiol Regul Integr Comp Physiol 301 (4): R1067‐77, 2011.
 307. Li XC, Campbell DJ, Ohishi M, Yuan S, Zhuo JL. AT1 receptor‐activated signaling mediates angiotensin IV‐induced renal cortical vasoconstriction in rats. Am J Physiol Renal Physiol 290: F1024‐F1033, 2006.
 308. Li XC, Carretero OA, Navar LG, Zhuo JL. AT1 receptor‐mediated accumulation of extracellular angiotensin II in proximal tubule cells: Role of cytoskeleton microtubules and tyrosine phosphatases. Am J Physiol Renal Physiol 291: F375‐F383, 2006.
 309. Li XC, Cook JL, Rubera I, Tauc M, Zhang F, Zhuo JL. Intrarenal transfer of an intracellular cyan fluorescent fusion of angiotensin II selectively in proximal tubules increases blood pressure in rats and mice. Am J Physiol Renal Physiol 300: F1076‐F1088, 2011.
 310. Li XC, Hopfer U, Zhuo JL. AT1 receptor‐mediated uptake of angiotensin II and NHE‐3 expression in proximal tubule cells through the microtubule‐dependent endocytic pathway. Am J Physiol Renal Physiol 297: F1342‐F1352, 2009.
 311. Li XC, Zhuo JL. Selective knockdown of AT1 receptors by RNA interference inhibits Val5‐Ang II endocytosis and NHE‐3 expression in immortalized rabbit proximal tubule cells. Am J Physiol Cell Physiol. 293, C367‐C378. 2007.
 312. Li XC, Zhuo JL. Phosphoproteomic analysis of AT1 receptor‐mediated signaling responses in proximal tubules of angiotensin II‐induced hypertensive rats. Kidney Int 80: 620‐632, 2011.
 313. Licht C, Laghmani K, Yanagisawa M, Preisig PA, Alpern RJ. An autocrine role for endothelin‐1 in the regulation of proximal tubule NHE3. Kidney Int 65: 1320‐1326, 2004.
 314. Lin HY, Kaji EH, Winkel GK, Ives HE, Lodish HF. Cloning and functional expression of a vascular smooth muscle endothelin 1 receptor. Proc Natl Acad Sci U S A 88: 3185‐3189, 1991.
 315. Litchfield JB, Bott PA. Micropuncture study of renal excretion of water, K, Na, and Cl in the rat. Am J Physiol 203: 667‐670, 1962.
 316. Liu FY, Cogan MG. Angiotensin II stimulation of hydrogen ion secretion in the rat early proximal tubule. Modes of action, mechanism, and kinetics. J Clin Invest 82: 601‐607, 1988.
 317. Liu FY, Cogan MG. Atrial natriuretic factor does not inhibit basal or angiotensin II‐ stimulated proximal transport. Am J Physiol 255: F434‐F437, 1988.
 318. Liu FY, Cogan MG. Role of angiotensin II in glomerulotubular balance. Am J Physiol 259: F72‐F79, 1990.
 319. Liu FY, Cogan MG. Role of protein kinase C in proximal bicarbonate absorption and angiotensin signaling. Am J Physiol 258: F927‐F933, 1990.
 320. Liu FY, Cogan MG, Rector FC, Jr. Axial heterogeneity in the rat proximal convoluted tubule. II. Osmolality and osmotic water permeability. Am J Physiol 247: F822‐F826, 1984.
 321. Liu J, Kesiry R, Periyasamy SM, Malhotra D, Xie Z, Shapiro JI. Ouabain induces endocytosis of plasmalemmal Na/K‐ATPase in LLC‐PK1 cells by a clathrin‐dependent mechanism. Kidney Int 66: 227‐241, 2004.
 322. Liu J, Liang M, Liu L, Malhotra D, Xie Z, Shapiro JI. Ouabain‐induced endocytosis of the plasmalemmal Na/K‐ATPase in LLC‐PK1 cells requires caveolin‐1. Kidney Int 67: 1844‐1854, 2005.
 323. Liu J, Yan Y, Liu L, Xie Z, Malhotra D, Joe B, Shapiro JI. Impairment of Na/K‐ATPase Signaling in Renal Proximal Tubule Contributes to Dahl Salt‐sensitive Hypertension. J Biol Chem 286: 22806‐22813, 2011.
 324. Lorenz JN, Schultheis PJ, Traynor T, Shull GE, Schnermann J. Micropuncture analysis of single‐nephron function in NHE3‐deficient mice. Am J Physiol 277: F447‐F453, 1999.
 325. Lorenzen M, Lee CO, Windhager EE. Cytosolic Ca2+ and Na+ activities in perfused proximal tubules of Necturus kidney. Am J Physiol 247: F93‐102, 1984.
 326. Luft FC. Renalase, a catecholamine‐metabolizing hormone from the kidney. Cell Metab 1: 358‐360, 2005.
 327. Luyckx VA, Brenner BM. Low birth weight, nephron number, and kidney disease. Kidney Int Suppl S68‐S77, 2005.
 328. Ly JP, Onay T, Sison K, Sivaskandarajah G, Sabbisetti V, Li L, Bonventre JV, Flenniken A, Paragas N, Barasch JM, Adamson SL, Osborne L, Rossant J, Schnermann J, Quaggin SE. The sweet pee model for Sglt2 mutation. J Am Soc Nephrol 22: 113‐123, 2011.
 329. Lytton J. Na+/Ca2+ exchangers: Three mammalian gene families control Ca2+ transport. Biochem J 406: 365‐382, 2007.
 330. Ma T, Yang B, Gillespie A, Carlson EJ, Epstein CJ, Verkman AS. Severely impaired urinary concentrating ability in transgenic mice lacking aquaporin‐1 water channels. J Biol Chem 273: 4296‐4299, 1998.
 331. Maack T, Camargo MJ, Kleinert HD, Laragh JH, Atlas SA. Atrial natriuretic factor: Structure and functional properties. Kidney Int 27: 607‐615, 1985.
 332. Maddox DA, Gennari FJ. The early proximal tubule: A high‐capacity delivery‐responsive reabsorptive site. Am J Physiol 252: F573‐F584, 1987.
 333. Madhun ZT, Goldthwait DA, McKay D, Hopfer U, Douglas JG. An epoxygenase metabolite of arachidonic acid mediates angiotensin II‐induced rises in cytosolic calcium in rabbit proximal tubule epithelial cells. J Clin Invest 88: 456‐461, 1991.
 334. Madjdpour C, Bacic D, Kaissling B, Murer H, Biber J. Segment‐specific expression of sodium‐phosphate cotransporters NaPi‐IIa and ‐IIc and interacting proteins in mouse renal proximal tubules. Pflugers Arch 448: 402‐410, 2004.
 335. Madsen KM, Nielsen S, Tisher CC. Anatomy of the kidney. In: Brenner BM, editor. Brenner and Rector's The Kidney. Saunders, An Imprint of Elsevier, Philadelphia. pp. 25‐90, 2008.
 336. Maduwegedera D, Kett MM, Flower RL, Lambert GW, Bertram JF, Wintour EM, Denton KM. Sex differences in postnatal growth and renal development in offspring of rabbit mothers with chronic secondary hypertension. Am J Physiol Regul Integr Comp Physiol 292: R706‐R714, 2007.
 337. Manhiani MM, Cormican MT, Brands MW. Chronic sodium‐retaining action of insulin in diabetic dogs. Am J Physiol Renal Physiol 300: F957‐F965, 2011.
 338. Marsenic O. Glucose control by the kidney: An emerging target in diabetes. Am J Kidney Dis 53: 875‐883, 2009.
 339. Mathisen O, Monclair T, Holdaas H, Kiil F. Bicarbonate as mediator of proximal tubular NaCl reabsorption and glomerulotubular balance. Scand J Clin Lab Invest 38: 7‐17, 1978.
 340. Matsusaka T, Niimura F, Shimizu A, Pastan I, Saito A, Kobori H, Nishiyama A, Ichikawa I. Liver angiotensinogen is the primary source of renal angiotensin II. J Am Soc Nephrol 23: 1181‐1189, 2012.
 341. Maunsbach AB, Boulpaep EL. Hydrostatic pressure changes related to paracellular shunt ultrastructure in proximal tubule. Kidney Int 17: 732‐748, 1980.
 342. McDonough AA. Mechanisms of proximal tubule sodium transport regulation that link extracellular fluid volume and blood pressure. Am J Physiol Regul Integr Comp Physiol 298: R851‐R861, 2010.
 343. McDonough AA, Leong PK, Yang LE. Mechanisms of pressure natriuresis: How blood pressure regulates renal sodium transport. Ann N Y Acad Sci 986: 669‐677, 2003.
 344. Mendelsohn FA. Evidence for the local occurrence of angiotensin II in rat kidney and its modulation by dietary sodium intake and converting enzyme blockade. Clin Sci (Lond) 57: 173‐179, 1979.
 345. Mendelsohn FA. Angiotensin II: Evidence for its role as an intrarenal hormone. Kidney Int Suppl 12: S78‐S81, 1982.
 346. Mendelsohn FA, Allen AM, Chai SY, Sexton PM, Figdor R. Overlapping distributions of receptors for atrial natriuretic peptide and angiotensin II visualized by in vitro autoradiography: Morphological basis of physiological antagonism. Can J Physiol Pharmacol 65: 1517‐1521, 1987.
 347. Menini S, Ricci C, Iacobini C, Bianchi G, Pugliese G, Pesce C. Glomerular number and size in Milan hypertensive and normotensive rats: Their relationship to susceptibility and resistance to hypertension and renal disease. J Hypertens 22: 2185‐2192, 2004.
 348. Mercer RW, Biemesderfer D, Bliss DP, Jr., Collins JH, Forbush B, III. Molecular cloning and immunological characterization of the gamma polypeptide, a small protein associated with the Na,K‐ATPase. J Cell Biol 121: 579‐586, 1993.
 349. Mimran A, Casellas D. The renin‐angiotensin system and nephron function heterogeneity. Kidney Int Suppl 20: S57‐S63, 1987.
 350. Miyazaki E, Sakaguchi M, Wakabayashi S, Shigekawa M, Mihara K. NHE6 protein possesses a signal peptide destined for endoplasmic reticulum membrane and localizes in secretory organelles of the cell. J Biol Chem 276: 49221‐49227, 2001.
 351. Moe OW. Acute regulation of proximal tubule apical membrane Na‐H exchanger NHE‐3: role of phosphorylation, protein trafficking, and regulatory factors. J Am Soc Nephrol 10: 2412‐2425, 1999.
 352. Molitoris BA, Dahl R, Geerdes A. Cytoskeleton disruption and apical redistribution of proximal tubule Na(+)‐K(+)‐ATPase during ischemia. Am J Physiol 263: F488‐F495, 1992.
 353. Moran A, Handler JS, Turner RJ. Na+‐dependent hexose transport in vesicles from cultured renal epithelial cell line. Am J Physiol 243: C293‐C298, 1982.
 354. Morgan T, Berliner RW. In vivo perfusion of proximal tubules of the rat: Glomerulotubular balance. Am J Physiol 217: 992‐997, 1969.
 355. Mori K, Ogawa Y, Ebihara K, Tamura N, Tashiro K, Kuwahara T, Mukoyama M, Sugawara A, Ozaki S, Tanaka I, Nakao K. Isolation and characterization of CA XIV, a novel membrane‐bound carbonic anhydrase from mouse kidney. J Biol Chem 274: 15701‐15705, 1999.
 356. Moseley AE, Lieske SP, Wetzel RK, James PF, He S, Shelly DA, Paul RJ, Boivin GP, Witte DP, Ramirez JM, Sweadner KJ, Lingrel JB. The Na,K‐ATPase alpha 2 isoform is expressed in neurons, and its absence disrupts neuronal activity in newborn mice. J Biol Chem 278: 5317‐5324, 2003.
 357. Mount DB, Yu ASL. Transport of inorganic solutes: Sodium, chloride, potassium, magnesium, calcium and phosphate. Brenner: Brenner and Rector's The Kidney. St. Louis: Saunders, 2007.
 358. Mullins LJ. Steady‐state calcium fluxes: Membrane versus mitochondrial control of ionized calcium in axoplasm. Fed Proc 35: 2583‐2588, 1976.
 359. Murawski IJ, Maina RW, Gupta IR. The relationship between nephron number, kidney size and body weight in two inbred mouse strains. Organogenesis 6: 189‐194, 2010.
 360. Murer H, Hopfer U, Kinne R. Sodium/proton antiport in brush‐border‐membrane vesicles isolated from rat small intestine and kidney. Biochem J 154: 597‐604, 1976.
 361. Murray RD, Itoh S, Inagami T, Misono K, Seto S, Scicli AG, Carretero OA. Effects of synthetic atrial natriuretic factor in the isolated perfused rat kidney. Am J Physiol 249: F603‐F609, 1985.
 362. Murtazina R, Kovbasnjuk O, Zachos NC, Li X, Chen Y, Hubbard A, Hogema BM, Steplock D, Seidler U, Hoque KM, Tse CM, De Jonge HR, Weinman EJ, Donowitz M. Tissue‐specific regulation of sodium/proton exchanger isoform 3 activity in Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) null mice. cAMP inhibition is differentially dependent on NHERF1 and exchange protein directly activated by cAMP in ileum versus proximal tubule. J Biol Chem 282: 25141‐25151, 2007.
 363. Myers BD, Deen WM, Brenner BM. Effects of norepinephrine and angiotensin II on the determinants of glomerular ultrafiltration and proximal tubule fluid reabsorption in the rat. Circ Res 37: 101‐110, 1975.
 364. Nair S, Wilding JP. Sodium glucose cotransporter 2 inhibitors as a new treatment for diabetes mellitus. J Clin Endocrinol Metab 95: 34‐42, 2010.
 365. Nakamura N, Tanaka S, Teko Y, Mitsui K, Kanazawa H. Four Na+/H+ exchanger isoforms are distributed to Golgi and post‐Golgi compartments and are involved in organelle pH regulation. J Biol Chem 280: 1561‐1572, 2005.
 366. Nakamuta M, Takayanagi R, Sakai Y, Sakamoto S, Hagiwara H, Mizuno T, Saito Y, Hirose S, Yamamoto M, Nawata H. Cloning and sequence analysis of a cDNA encoding human non‐selective type of endothelin receptor. Biochem Biophys Res Commun 177: 34‐39, 1991.
 367. Navar LG, Carmines PK, Huang WC, Mitchell KD. The tubular effects of angiotensin II. Kidney Int Suppl 20: S81‐S88, 1987.
 368. Navar LG, Imig JD, Zou L, Wang CT. Intrarenal production of angiotensin II. Semin Nephrol 17: 412‐422, 1997.
 369. Navar LG, Inscho EW, Majid SA, Imig JD, Harrison‐Bernard LM, Mitchell KD. Paracrine regulation of the renal microcirculation. Physiol Rev 76: 425‐536, 1996.
 370. Navar LG, Kobori H, Prieto‐Carrasquero M. Intrarenal Angiotensin II and Hypertension. Curr Hypertens Rep 5: 135‐143, 2003.
 371. Navar LG, Lewis L, Hymel A, Braam B, Mitchell KD. Tubular fluid concentrations and kidney contents of angiotensins I and II in anesthetized rats. J Am Soc Nephrol 5: 1153‐1158, 1994.
 372. Navar LG, Satou R, Gonzalez‐Villalobos RA. The increasing complexity of the intratubular Renin‐Angiotensin system. J Am Soc Nephrol 23: 1130‐1132, 2012.
 373. Navar LG, Schafer JA. Comment on “Lithium clearance: A new research area. News Physiol Sci 2: 34‐35, 1987.
 374. Navar LG, Zou L, Von Thun A, Tarng WC, Imig JD, Mitchell KD. Unraveling the mystery of Goldblatt hypertension. News Physiol Sci 13: 170‐176, 1998.
 375. Needleman P, Adams SP, Cole BR, Currie MG, Geller DM, Michener ML, Saper CB, Schwartz D, Standaert DG. Atriopeptins as cardiac hormones. Hypertension 7: 469‐482, 1985.
 376. Neumann KH, Rector FC, Jr. Mechanism of NaCl and water reabsorption in the proximal convoluted tubule of rat kidney. J Clin Invest 58: 1110‐1118, 1976.
 377. Nicoll DA, Longoni S, Philipson KD. Molecular cloning and functional expression of the cardiac sarcolemmal Na(+)‐Ca2+ exchanger. Science 250: 562‐565, 1990.
 378. Nonoguchi H, Sands JM, Knepper MA. ANF inhibits NaCl and fluid absorption in cortical collecting duct of rat kidney. Am J Physiol 256: F179‐F186, 1989.
 379. Noonan WT, Woo AL, Nieman ML, Prasad V, Schultheis PJ, Shull GE, Lorenz JN. Blood pressure maintenance in NHE3‐deficient mice with transgenic expression of NHE3 in small intestine. Am J Physiol Regul Integr Comp Physiol 288: R685‐R691, 2005.
 380. Nurnberger A, Rabiger M, Mack A, Diaz J, Sokoloff P, Muhlbauer B, Luippold G. Subapical localization of the dopamine D3 receptor in proximal tubules of the rat kidney. J Histochem Cytochem 52: 1647‐1655, 2004.
 381. O'Connell DP, Botkin SJ, Ramos SI, Sibley DR, Ariano MA, Felder RA, Carey RM. Localization of dopamine D1A receptor protein in rat kidneys. Am J Physiol 268: F1185‐F1197, 1995.
 382. O'Connell DP, Vaughan CJ, Aherne AM, Botkin SJ, Wang ZQ, Felder RA, Carey RM. Expression of the dopamine D3 receptor protein in the rat kidney. Hypertension 32: 886‐895, 1998.
 383. Ogawa Y, Nakao K, Arai H, Nakagawa O, Hosoda K, Suga S, Nakanishi S, Imura H. Molecular cloning of a non‐isopeptide‐selective human endothelin receptor. Biochem Biophys Res Commun 178: 248‐255, 1991.
 384. Oliver J, Macdowell M. The structural and functional aspects of the handling of glucose by the nephrons and the kidney and their correlation by means of structural‐functional equivalents. J Clin Invest 40: 1093‐1112, 1961.
 385. Olsen NV, Aachmann‐Andersen NJ, Oturai P, Munch‐Andersen T, Borno A, Hulston C, Holstein‐Rathlou NH, Robach P, Lundby C. Erythropoietin down‐regulates proximal renal tubular reabsorption and causes a fall in glomerular filtration rate in humans. J Physiol 589: 1273‐1281, 2011.
 386. Ong AC, Jowett TP, Moorhead JF, Owen JS. Human high density lipoproteins stimulate endothelin‐1 release by cultured human renal proximal tubular cells. Kidney Int 46: 1315‐1321, 1994.
 387. Orlowski J. Heterologous expression and functional properties of amiloride high affinity (NHE‐1) and low affinity (NHE‐3) isoforms of the rat Na/H exchanger. J Biol Chem 268: 16369‐16377, 1993.
 388. Orlowski J, Kandasamy RA, Shull GE. Molecular cloning of putative members of the Na/H exchanger gene family. cDNA cloning, deduced amino acid sequence, and mRNA tissue expression of the rat Na/H exchanger NHE‐1 and two structurally related proteins. J Biol Chem 267: 9331‐9339, 1992.
 389. Ozono R, O'Connell DP, Wang ZQ, Moore AF, Sanada H, Felder RA, Carey RM. Localization of the dopamine D1 receptor protein in the human heart and kidney. Hypertension 30: 725‐729, 1997.
 390. Ozono R, Wang ZQ, Moore AF, Inagami T, Siragy HM, Carey RM. Expression of the subtype 2 angiotensin (AT2) receptor protein in rat kidney. Hypertension 30: 1238‐1246, 1997.
 391. Padia SH, Howell NL, Siragy HM, Carey RM. Renal angiotensin type 2 receptors mediate natriuresis via angiotensin III in the angiotensin II type 1 receptor‐blocked rat. Hypertension 47: 537‐544, 2006.
 392. Padia SH, Kemp BA, Howell NL, Gildea JJ, Keller SR, Carey RM. Intrarenal angiotensin III infusion induces natriuresis and angiotensin type 2 receptor translocation in Wistar‐Kyoto but not in spontaneously hypertensive rats. Hypertension 53: 338‐343, 2009.
 393. Padia SH, Kemp BA, Howell NL, Keller SR, Gildea JJ, Carey RM. Mechanisms of dopamine D(1) and angiotensin type 2 receptor interaction in natriuresis. Hypertension 59: 437‐445, 2012.
 394. Padia SH, Kemp BA, Howell NL, Siragy HM, Fournie‐Zaluski MC, Roques BP, Carey RM. Intrarenal aminopeptidase N inhibition augments natriuretic responses to angiotensin III in angiotensin type 1 receptor‐blocked rats. Hypertension 49: 625‐630, 2007.
 395. Palmer LG, Alpern RJ, Seldin DW. Physiology and pathophysiology of sodium retention and wastage. In: Alpern RJ, Hebert SC, editors. The Kidney: Physiology and Pathophysiology. Burlington, San Diego, London: Academic Press, 2008.
 396. Pandey KN. Biology of natriuretic peptides and their receptors. Peptides 26: 901‐932, 2005.
 397. Pandey KN. Emerging Roles of Natriuretic Peptides and their Receptors in Pathophysiology of Hypertension and Cardiovascular Regulation. J Am Soc Hypertens 2: 210‐226, 2008.
 398. Panico C, Luo Z, Damiano S, Artigiano F, Gill P, Welch WJ. Renal proximal tubular reabsorption is reduced in adult spontaneously hypertensive rats: Roles of superoxide and Na+/H+ exchanger 3. Hypertension 54: 1291‐1297, 2009.
 399. Pao AC, Bhargava A, Di SF, Quigley R, Shao X, Wang J, Thomas S, Zhang J, Shi M, Funder JW, Moe OW, Pearce D. Expression and role of serum and glucocorticoid‐regulated kinase 2 in the regulation of Na+/H+ exchanger 3 in the mammalian kidney. Am J Physiol Renal Physiol 299: F1496‐F1506, 2010.
 400. Parker MD, Boron WF. Sodium‐coupled bicarbonate transporters. In: Alpern RJ, Hebert SC, editors. Seldin and Giebisch's The Kidney: Physiology and Pathophysiology. London: Academic Press, 2008.
 401. Pelayo JC, Fildes RD, Eisner GM, Jose PA. Effects of dopamine blockade on renal sodium excretion. Am J Physiol 245: F247‐F253, 1983.
 402. Peng Y, Amemiya M, Yang X, Fan L, Moe OW, Yin H, Preisig PA, Yanagisawa M, Alpern RJ. ET(B) receptor activation causes exocytic insertion of NHE3 in OKP cells. Am J Physiol Renal Physiol 280: F34‐F42, 2001.
 403. Peng Y, Moe OW, Chu T, Preisig PA, Yanagisawa M, Alpern RJ. ETB receptor activation leads to activation and phosphorylation of NHE3. Am J Physiol 276: C938‐C945, 1999.
 404. Perico N, Cornejo RP, Benigni A, Malanchini B, Ladny JR, Remuzzi G. Endothelin induces diuresis and natriuresis in the rat by acting on proximal tubular cells through a mechanism mediated by lipoxygenase products. J Am Soc Nephrol 2: 57‐69, 1991.
 405. Periyasamy SM, Liu J, Tanta F, Kabak B, Wakefield B, Malhotra D, Kennedy DJ, Nadoor A, Fedorova OV, Gunning W, Xie Z, Bagrov AY, Shapiro JI. Salt loading induces redistribution of the plasmalemmal Na/K‐ATPase in proximal tubule cells. Kidney Int 67: 1868‐1877, 2005.
 406. Pesce C. Glomerular number and size: Facts and artefacts. Anat Rec 251: 66‐71, 1998.
 407. Peterson LN, de RC, Sonnenberg H, Levine DZ. Thick ascending limb response to dDAVP and atrial natriuretic factor in vivo. Am J Physiol 252: F374‐F381, 1987.
 408. Philipson KD, Nicoll DA, Ottolia M, Quednau BD, Reuter H, John S, Qiu Z. The Na+/Ca2+ exchange molecule: An overview. Ann N Y Acad Sci 976: 1‐10, 2002.
 409. Pinho MJ, Serrao MP, Gomes P, Hopfer U, Jose PA, Soares‐da‐Silva P. Over‐expression of renal LAT1 and LAT2 and enhanced L‐DOPA uptake in SHR immortalized renal proximal tubular cells. Kidney Int 66: 216‐226, 2004.
 410. Pittner J, Wolgast M, Casellas D, Persson AE. Increased shear stress‐released NO and decreased endothelial calcium in rat isolated perfused juxtamedullary nephrons. Kidney Int 67: 227‐236, 2005.
 411. Pollock DM. Dissecting the complex physiology of endothelin: New lessons from genetic models. Hypertension 56: 31‐33, 2010.
 412. Pritchard JB, Miller DS. Proximal tubular transport of organic anions and cations. In: Seldin DW, Giebisch G, editors. The Kidney: Physiology and Pathophysiology. New York: Raven Press, 1992.
 413. Pruijm M, Wuerzner G, Maillard M, Bovet P, Renaud C, Bochud M, Burnier M. Glomerular hyperfiltration and increased proximal sodium reabsorption in subjects with type 2 diabetes or impaired fasting glucose in a population of the African region. Nephrol Dial Transplant 25: 2225‐2231, 2010.
 414. Puelles VG, Hoy WE, Hughson MD, Diouf B, Douglas‐Denton RN, Bertram JF. Glomerular number and size variability and risk for kidney disease. Curr Opin Nephrol Hypertens 20: 7‐15, 2011.
 415. Purkerson JM, Kittelberger AM, Schwartz GJ. Basolateral carbonic anhydrase IV in the proximal tubule is a glycosylphosphatidylinositol‐anchored protein. Kidney Int 71: 407‐416, 2007.
 416. Purkerson JM, Schwartz GJ. The role of carbonic anhydrases in renal physiology. Kidney Int 71: 103‐115, 2007.
 417. Quamme GA, DIRKS JH. Micropuncture techniques. Kidney Int 30: 152‐165, 1986.
 418. Quinn MD, Marsh DJ. Peritubular capillary control of proximal tubule reabsorption in the rat. Am J Physiol 236: F478‐F487, 1979.
 419. Rakugi H, Ogihara T, Nakamaru M, Saito H, Shima J, Sakaguchi K, Kumahara Y. Renal interaction of atrial natriuretic peptide with angiotensin II: Glomerular and tubular effects. Clin Exp Pharmacol Physiol 16: 97‐107, 1989.
 420. Rakugi H, Ogihara T, Nakamaru M, Saito H, Shima J, Sakaguchi K, Kumahara Y. Role of angiotensin II in the renal response to atrial natriuretic peptide in normal subjects. J Cardiovasc Pharmacol 13 Suppl 6: S55‐S58, 1989.
 421. Rector FC, Jr. Sodium, bicarbonate, and chloride absorption by the proximal tubule. Am J Physiol 244: F461‐F471, 1983.
 422. Rector FC, Jr., Brunner FP, Seldin DW. Mechanism of glomerulotubular balance. I. Effect of aortic constriction and elevated ureteropelvic pressure on glomerular filtration rate, fractional reabsorption, transit time, and tubular size in the proximal tubule of the rat. J Clin Invest 45: 590‐602, 1966.
 423. Reilly AM, Harris PJ, Williams DA. Biphasic effect of angiotensin II on intracellular sodium concentration in rat proximal tubules. Am J Physiol 269: F374‐F380, 1995.
 424. Reilly RF, Shugrue CA. cDNA cloning of a renal Na+‐Ca2+ exchanger. Am J Physiol 262: F1105‐F1109, 1992.
 425. Reilly RF, Shugrue CA, Lattanzi D, Biemesderfer D. Immunolocalization of the Na+/Ca2+ exchanger in rabbit kidney. Am J Physiol 265: F327‐F332, 1993.
 426. Riquier‐Brison AD, Leong PK, Pihakaski‐Maunsbach K, McDonough AA. Angiotensin II stimulates trafficking of NHE3, NaPi2, and associated proteins into the proximal tubule microvilli. Am J Physiol Renal Physiol 298: F177‐F186, 2010.
 427. Rodicio J, Herrera‐Acosta J, Sellman JC, Rector FC, Jr. , Seldin DW. Studies on glomerulotubular balance during aortic constriction, ureteral obstruction and venous occlusion in hydropenic and saline‐loaded rats. Nephron 6: 437‐456, 1969.
 428. Roman RJ. Pressure diuresis mechanism in the control of renal function and arterial pressure. Fed Proc 45: 2878‐2884, 1986.
 429. Roman RJ. Pressure‐diuresis in volume‐expanded rats. Tubular reabsorption in superficial and deep nephrons. Hypertension 12: 177‐183, 1988.
 430. Romano G, Giagu P, Favret G, Bartoli E. Effect of endothelin 1 on proximal reabsorption and tubuloglomerular feedback. Kidney Blood Press Res 23: 360‐365, 2000.
 431. Romero MF. Molecular pathophysiology of SLC4 bicarbonate transporters. Curr Opin Nephrol Hypertens 14: 495‐501, 2005.
 432. Rostgaard J, Moller O. Localization of Na+, K+ ‐ATPase to the inside of the basolateral cell membranes of epithelial cells of proximal and distal tubules in rabbit kidney. Cell Tissue Res 212: 17‐28, 1980.
 433. Sackin H, Palmer LG. Electrophysiological analysis of transepithelial transport. In: Alpern RJ, Hebert SC, editors. Seldin and Giebisch's The Kidney: Physiology and Pathophysiology. London: Academic Press, 2008.
 434. Sakamoto A, Yanagisawa M, Sakurai T, Takuwa Y, Yanagisawa H, Masaki T. Cloning and functional expression of human cDNA for the ETB endothelin receptor. Biochem Biophys Res Commun 178: 656‐663, 1991.
 435. Sakurai T, Yanagisawa M, Takuwa Y, Miyazaki H, Kimura S, Goto K, Masaki T. Cloning of a cDNA encoding a non‐isopeptide‐selective subtype of the endothelin receptor. Nature 348: 732‐735, 1990.
 436. Salazar FJ, Granger JP, Fiksen‐Olsen MJ, Bentley MD, Romero JC. Possible modulatory role of angiotensin II on atrial peptide‐induced natriuresis. Am J Physiol 253: F880‐F883, 1987.
 437. Samuel T, Hoy WE, Douglas‐Denton R, Hughson MD, Bertram JF. Determinants of glomerular volume in different cortical zones of the human kidney. J Am Soc Nephrol 16: 3102‐3109, 2005.
 438. Sardet C, Franchi A, Pouyssegur J. Molecular cloning, primary structure, and expression of the human growth factor‐activatable Na+/H+ antiporter. Cell 56: 271‐280, 1989.
 439. Schafer JA. Robert F. Pitts Memorial Lecture. Mechanisms coupling the absorption of solutes and water in the proximal nephron. Kidney Int 25: 708‐716, 1984.
 440. Schafer JA, Andreoli TE. Rheogenic and passive Na+ absorption by the proximal nephron. Annu Rev Physiol 41: 211‐227, 1979.
 441. Schafer JA, Troutman SL, Andreoli TE. Volume reabsorption, transepithelial potential differences, and ionic permeability properties in mammalian superficial proximal straight tubules. J Gen Physiol 64: 582‐607, 1974.
 442. Scherzer P, Popovtzer MM. Segmental localization of mRNAs encoding Na+‐K+‐ATPase alpha(1)‐ and beta(1)‐subunits in diabetic rat kidneys using RT‐PCR. Am J Physiol Renal Physiol 282: F492‐F500, 2002.
 443. Schneider MP, Boesen EI, Pollock DM. Contrasting actions of endothelin ET(A) and ET(B) receptors in cardiovascular disease. Annu Rev Pharmacol Toxicol 47: 731‐759, 2007.
 444. Schnermann J. Sodium transport deficiency and sodium balance in gene‐targeted mice. Acta Physiol Scand 173: 59‐66, 2001.
 445. Schnermann J, Chou CL, Ma T, Traynor T, Knepper MA, Verkman AS. Defective proximal tubular fluid reabsorption in transgenic aquaporin‐1 null mice. Proc Natl Acad Sci U S A 95: 9660‐9664, 1998.
 446. Schnermann J, Wahl M, Liebau G, Fischbach H. Balance between tubular flow rate and net fluid reabsorption in the proximal convolution of the rat kidney. I. Dependency of reabsorptive net fluid flux upon proximal tubular surface area at spontaneous variations of filtration rate. Pflugers Arch 304: 90‐103, 1968.
 447. Schou M, Thomsen K, Vestergaard P. The renal lithium clearance and its correlations with other biological variables: Observations in a large group of physically healthy persons. Clin Nephrol 25: 207‐211, 1986.
 448. Schreuder MF, Nauta J. Prenatal programming of nephron number and blood pressure. Kidney Int 72: 265‐268, 2007.
 449. Schultheis PJ, Clarke LL, Meneton P, Miller ML, Soleimani M, Gawenis LR, Riddle TM, Duffy JJ, Doetschman T, Wang T, Giebisch G, Aronson PS, Lorenz JN, Shull GE. Renal and intestinal absorptive defects in mice lacking the NHE3 Na+/H+ exchanger. Nat Genet 19: 282‐285, 1998.
 450. Schulz A, Hansch J, Kuhn K, Schlesener M, Kossmehl P, Nyengaard JR, Wendt N, Huber M, Kreutz R. Nephron deficit is not required for progressive proteinuria development in the Munich Wistar Fromter rat. Physiol Genomics 35: 30‐35, 2008.
 451. Schuster VL, Kokko JP, Jacobson HR. Angiotensin II directly stimulates sodium transport in rabbit proximal convoluted tubules. J Clin Invest 73: 507‐515, 1984.
 452. Schuster VL, Seldin DW. Renal clearance. In: Seldin DW, Giebisch G, editors. The Kidney: Physiology and Pathophysiology. New York: Raven Press, 1985.
 453. Schwartz GJ, Kittelberger AM, Barnhart DA, Vijayakumar S. Carbonic anhydrase IV is expressed in H(+)‐secreting cells of rabbit kidney. Am J Physiol Renal Physiol 278: F894‐F904, 2000.
 454. Seri I. Dopamine and natriuresis. Mechanism of action and developmental aspects. Am J Hypertens 3: 82S‐86S, 1990.
 455. Serneri GG, Modesti PA, Cecioni I, Biagini D, Migliorini A, Costoli A, Colella A, Naldoni A, Paoletti P. Plasma endothelin and renal endothelin are two distinct systems involved in volume homeostasis. Am J Physiol 268: H1829‐H1837, 1995.
 456. Sexton PM, Zhuo J, Mendelsohn FA. Localization and regulation of renal receptors for angiotensin II and atrial natriuretic peptide. Tohoku J Exp Med 166: 41‐56, 1992.
 457. Shamraj OI, Lingrel JB. A putative fourth Na+,K+‐ATPase alpha‐subunit gene is expressed in testis. Proc Natl Acad Sci U S A 91: 12952‐12956, 1994.
 458. Sheng S, Johnson JP, Kleyman TR. Epithelial Na+ channels. In: Alpern RJ, Hebert SC, editors. Seldin and Giebisch' The Kidney: Physiology and Pathophysiology. London: Academic Press, 2008.
 459. Shenolikar S, Voltz JW, Minkoff CM, Wade JB, Weinman EJ. Targeted disruption of the mouse NHERF‐1 gene promotes internalization of proximal tubule sodium‐phosphate cotransporter type IIa and renal phosphate wasting. Proc Natl Acad Sci U S A 99: 11470‐11475, 2002.
 460. Shichiri M, Hirata Y, Ando K, Emori T, Ohta K, Kimoto S, Ogura M, Inoue A, Marumo F. Plasma endothelin levels in hypertension and chronic renal failure. Hypertension 15: 493‐496, 1990.
 461. Shirley DG, Walter SJ, Thomsen K. A comparison of micropuncture and lithium clearance methods in the assessment of renal tubular function in rats with diabetes insipidus. Pflugers Arch 399: 266‐270, 1983.
 462. Shull GE, Greeb J, Lingrel JB. Molecular cloning of three distinct forms of the Na+,K+‐ATPase alpha‐subunit from rat brain. Biochemistry 25: 8125‐8132, 1986.
 463. Shull GE, Lane LK, Lingrel JB. Amino‐acid sequence of the beta‐subunit of the (Na+ ‐ K+)ATPase deduced from a cDNA. Nature 321: 429‐431, 1986.
 464. Shull GE, Lingrel JB. Molecular cloning of the rat stomach (H+ + K+)‐ATPase. J Biol Chem 261: 16788‐16791, 1986.
 465. Shull GE, Schwartz A, Lingrel JB. Amino‐acid sequence of the catalytic subunit of the (Na+ ‐ K+)ATPase deduced from a complementary DNA. Nature 316: 691‐695, 1985.
 466. Silverman M. Glucose reabsorption in the kidney:glucouria: Molecular mechanism of Na+/glucose cotransport. In: Alpern RJ, Hebert SC, editors. Seldin and Giebisch's The Kidney: Physiology and Pathophysiology. London: Academic Press, 2008.
 467. Sindic A, Chang MH, Mount DB, Romero MF. Renal physiology of SLC26 anion exchangers. Curr Opin Nephrol Hypertens 16: 484‐490, 2007.
 468. Skou JC. The influence of some cations on an adenosine triphosphatase from peripheral nerves. Biochim Biophys Acta 23: 394‐401, 1957.
 469. Sly WS, Hewett‐Emmett D, Whyte MP, Yu YS, Tashian RE. Carbonic anhydrase II deficiency identified as the primary defect in the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. Proc Natl Acad Sci U S A 80: 2752‐2756, 1983.
 470. Sly WS, Hu PY. Human carbonic anhydrases and carbonic anhydrase deficiencies. Annu Rev Biochem 64: 375‐401.: 375‐401, 1995.
 471. Sly WS, Whyte MP, Sundaram V, Tashian RE, Hewett‐Emmett D, Guibaud P, Vainsel M, Baluarte HJ, Gruskin A, Al‐Mosawi M. Carbonic anhydrase II deficiency in 12 families with the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. N Engl J Med 313: 139‐145, 1985.
 472. Smith HW. The Kidney: Structure and Function in Health and Disease. New York: Oxford University Press, 1951, pp. 460‐495.
 473. Soleimani M, Singh G, Bizal GL, Gullans SR, McAteer JA. Na+/H+ exchanger isoforms NHE‐2 and NHE‐1 in inner medullary collecting duct cells. Expression, functional localization, and differential regulation. J Biol Chem 269: 27973‐27978, 1994.
 474. Solomon LR, Atherton JC, Bobinski H, Cottam SL, Gray C, Green R, Watts HJ. Effect of a meal containing protein on lithium clearance and plasma immunoreactive atrial natriuretic peptide in man. Clin Sci (Lond) 75: 151‐157, 1988.
 475. Sonnenberg H, Chong CK, Veress AT. Cardiac atrial factor–an endogenous diuretic? Can J Physiol Pharmacol 59: 1278‐1279, 1981.
 476. Sonnenberg H, Cupples WA, de Bold AJ, Veress AT. Intrarenal localization of the natriuretic effect of cardiac atrial extract. Can J Physiol Pharmacol 60: 1149‐1152, 1982.
 477. Sonnenberg H, Honrath U, Chong CK, Wilson DR. Atrial natriuretic factor inhibits sodium transport in medullary collecting duct. Am J Physiol 250: F963‐F966, 1986.
 478. Sorensen SS, Madsen JK, Pedersen EB. Systemic and renal effect of intravenous infusion of endothelin‐1 in healthy human volunteers. Am J Physiol 266: F411‐F418, 1994.
 479. Souster LP, Emery JL. The sizes of renal glomeruli in fetuses and infants. J Anat 130: 595‐602, 1980.
 480. Staudacher T, Pech B, Tappe M, Gross G, Muhlbauer B, Luippold G. Arterial blood pressure and renal sodium excretion in dopamine D3 receptor knockout mice. Hypertens Res 30: 93‐101, 2007.
 481. Steele TH, Manuel MA, Newton M, Boner G. Renal lithium reabsorption in man: Physiologic and pharmacologic determinants. Am J Med Sci 269: 349‐363, 1975.
 482. Stein JH, Reineck JH, Osgood RW, Ferris TF. Effect of acetylcholine on proximal tubular sodium reabsorption in the dog. Am J Physiol 220: 227‐232, 1971.
 483. Sterio DC. The unbiased estimation of number and sizes of arbitrary particles using the disector. J Microsc 134: 127‐136, 1984.
 484. Su Z, Zimpelmann J, Burns KD. Angiotensin‐(1‐7) inhibits angiotensin II‐stimulated phosphorylation of MAP kinases in proximal tubular cells. Kidney Int 69: 2212‐2218, 2006.
 485. Sun D, Wilborn TW, Schafer JA. Dopamine D4 receptor isoform mRNA and protein are expressed in the rat cortical collecting duct. Am J Physiol 275: F742‐F751, 1998.
 486. Szabo AJ, Muller V, Chen GF, Samsell LJ, Erdely A, Baylis C. Nephron number determines susceptibility to renal mass reduction‐induced CKD in Lewis and Fisher 344 rats: Implications for development of experimentally induced chronic allograft nephropathy. Nephrol Dial Transplant 23: 2492‐2495, 2008.
 487. Takada T, Yamamoto A, Omori K, Tashiro Y. Quantitative immunogold localization of Na, K‐ATPase along rat nephron. Histochemistry 98: 183‐197, 1992.
 488. Takemoto F, Uchida S, Ogata E, Kurokawa K. Endothelin‐1 and endothelin‐3 binding to rat nephrons. Am J Physiol 264: F827‐F832, 1993.
 489. Tang SS, Jung F, Diamant D, Brown D, Bachinsky D, Hellman P, Ingelfinger JR. Temperature‐sensitive SV40 immortalized rat proximal tubule cell line has functional renin‐angiotensin system. Am J Physiol 268: F435‐F446, 1995.
 490. Taylor A, Windhager EE. Possible role of cytosolic calcium and Na‐Ca exchange in regulation of transepithelial sodium transport. Am J Physiol 236: F505‐F512, 1979.
 491. Tendron A, Decramer S, Justrabo E, Gouyon JB, Semama DS, Gilbert T. Cyclosporin A administration during pregnancy induces a permanent nephron deficit in young rabbits. J Am Soc Nephrol 14: 3188‐3196, 2003.
 492. Thomsen K. Lithium clearance: A new method for determining proximal and distal tubular reabsorption of sodium and water. Nephron 37: 217‐223, 1984.
 493. Thomsen K, Holstein‐Rathlou NH, Leyssac PP. Comparison of three measures of proximal tubular reabsorption: Lithium clearance, occlusion time, and micropuncture. Am J Physiol 241: F348‐F355, 1981.
 494. Thomsen K, Olesen OV. Renal lithium clearance as a measure of the delivery of water and sodium from the proximal tubule in humans. Am J Med Sci 288: 158‐161, 1984.
 495. Thomson SC, Blantz RC. Glomerulotubular balance, tubuloglomerular feedback, and salt homeostasis. J Am Soc Nephrol 19: 2272‐2275, 2008.
 496. Thomson SC, Deng A, Wead L, Richter K, Blantz RC, Vallon V. An unexpected role for angiotensin II in the link between dietary salt and proximal reabsorption. J Clin Invest 116: 1110‐1116, 2006.
 497. Torielli L, Tivodar S, Montella RC, Iacone R, Padoani G, Tarsini P, Russo O, Sarnataro D, Strazzullo P, Ferrari P, Bianchi G, Zurzolo C. alpha‐Adducin mutations increase Na/K pump activity in renal cells by affecting constitutive endocytosis: Implications for tubular Na reabsorption. Am J Physiol Renal Physiol 295: F478‐F487, 2008.
 498. Tse CM, Brant SR, Walker MS, Pouyssegur J, Donowitz M. Cloning and sequencing of a rabbit cDNA encoding an intestinal and kidney‐specific Na+/H+ exchanger isoform (NHE‐3). J Biol Chem 267: 9340‐9346, 1992.
 499. Tse CM, Levine SA, Yun CH, Brant SR, Pouyssegur J, Montrose MH, Donowitz M. Functional characteristics of a cloned epithelial Na+/H+ exchanger (NHE3): resistance to amiloride and inhibition by protein kinase C. Proc Natl Acad Sci U S A 90: 9110‐9114, 1993.
 500. Tse CM, Levine SA, Yun CH, Montrose MH, Little PJ, Pouyssegur J, Donowitz M. Cloning and expression of a rabbit cDNA encoding a serum‐activated ethylisopropylamiloride‐resistant epithelial Na+/H+ exchanger isoform (NHE‐2). J Biol Chem 268: 11917‐11924, 1993.
 501. Tse CM, Ma AI, Yang VW, Watson AJ, Levine S, Montrose MH, Potter J, Sardet C, Pouyssegur J, Donowitz M. Molecular cloning and expression of a cDNA encoding the rabbit ileal villus cell basolateral membrane Na+/H+ exchanger. EMBO J 10: 1957‐1967, 1991.
 502. Tsuruoka S, Kittelberger AM, Schwartz GJ. Carbonic anhydrase II and IV mRNA in rabbit nephron segments: Stimulation during metabolic acidosis. Am J Physiol 274: F259‐F267, 1998.
 503. Tucker BJ, Blantz RC. Determinants of proximal tubular reabsorption as mechanisms of glomerulotubular balance. Am J Physiol 235: F142‐F150, 1978.
 504. Turner RJ, Moran A. Heterogeneity of sodium‐dependent D‐glucose transport sites along the proximal tubule: Evidence from vesicle studies. Am J Physiol 242: F406‐F414, 1982.
 505. Uchida S, Takemoto F, Ogata E, Kurokawa K. Detection of endothelin‐1 mRNA by RT‐PCR in isolated rat renal tubules. Biochem Biophys Res Commun 188: 108‐113, 1992.
 506. Uchida S, Takemoto F, Ogata E, Kurokawa K. Endothelin‐1 and ‐3 binding to ETB receptors in rat renal tubules. J Cardiovasc Pharmacol 22 (Suppl 8): S177‐S180, 1993.
 507. Ujiie K, Terada Y, Nonoguchi H, Shinohara M, Tomita K, Marumo F. Messenger RNA expression and synthesis of endothelin‐1 along rat nephron segments. J Clin Invest 90: 1043‐1048, 1992.
 508. Ullrich KJ, Greger R. Approaches to the study of tubular transport functions. In: Seldin DW, Giebisch G, editors. The Kidney: Physiology and Pathophysiology. New York: Raven Press, 1985.
 509. Ullrich KJ, Rumrich G, Kloss S. Specificity and sodium dependence of the active sugar transport in the proximal convolution of the rat kidney. Pflugers Arch 351: 35‐48, 1974.
 510. Ussing HH, Eskesen K. Mechanism of isotonic water transport in glands. Acta Physiol Scand 136: 443‐454, 1989.
 511. Ussing HH, Lind F, Larsen EH. Ion secretion and isotonic transport in frog skin glands. J Membr Biol 152: 101‐110, 1996.
 512. Vallon V. Micropuncturing the nephron. Pflugers Arch 458: 189‐201, 2009.
 513. Vallon V. The proximal tubule in the pathophysiology of the diabetic kidney. Am J Physiol Regul Integr Comp Physiol 300: R1009‐R1022, 2011.
 514. Vallon V, Platt KA, Cunard R, Schroth J, Whaley J, Thomson SC, Koepsell H, Rieg T. SGLT2 mediates glucose reabsorption in the early proximal tubule. J Am Soc Nephrol 22: 104‐112, 2011.
 515. Vallon V, Verkman AS, Schnermann J. Luminal hypotonicity in proximal tubules of aquaporin‐1‐knockout mice. Am J Physiol Renal Physiol 278: F1030‐F1033, 2000.
 516. van Kats JP, Schalekamp MA, Verdouw PD, Duncker DJ, Danser AH. Intrarenal angiotensin II: Interstitial and cellular levels and site of production. Kidney Int 60: 2311‐2317, 2001.
 517. Vives D, Farage S, Motta R, Lopes AG, Caruso‐Neves C. Atrial natriuretic peptides and urodilatin modulate proximal tubule Na(+)‐ATPase activity through activation of the NPR‐A/cGMP/PKG pathway. Peptides 31: 903‐908, 2010.
 518. Wade JB, Liu J, Coleman RA, Cunningham R, Steplock DA, Lee‐Kwon W, Pallone TL, Shenolikar S, Weinman EJ. Localization and interaction of NHERF isoforms in the renal proximal tubule of the mouse. Am J Physiol Cell Physiol 285: C1494‐C1503, 2003.
 519. Wagner CA, Geibel JP. Expression, function, and the regulation of Na+.K+‐ATPase in the kidney. In: Alpern RJ, Hebert SC, editors. Seldin and Giebisch's The Kidney: Physiology and Pathophysiology. London: Academic Press, 2008.
 520. Wakabayashi S, Shigekawa M, Pouyssegur J. Molecular physiology of vertebrate Na+/H+ exchangers. Physiol Rev 77: 51‐74, 1997.
 521. Walker AM, Bott PA, OLIVER J, MacDowell MC. The collection and analysis of fluid from single nephrons of the mammalian kidney. Am J Physiol 134: 580‐595, 1941.
 522. Walker AM, OLIVER J. Methods for the collection of fluid from single glomeruli and tubules of the mammalian kidney. Am J Physiol 134: 562‐579, 1941.
 523. Walter R, Helmle‐Kolb C, Forgo J, Binswanger U, Murer H. Stimulation of Na+/H+ exchange activity by endothelin in opossum kidney cells. Pflugers Arch 430: 137‐144, 1995.
 524. Wang D, Zhang H, Lang F, Yun CC. Acute activation of NHE3 by dexamethasone correlates with activation of SGK1 and requires a functional glucocorticoid receptor. Am J Physiol Cell Physiol 292: C396‐C404, 2007.
 525. Wang T. Flow‐activated transport events along the nephron. Curr Opin Nephrol Hypertens 15: 530‐536, 2006.
 526. Wang T, Chan YL. Mechanism of angiotensin II action on proximal tubular transport. J Pharmacol Exp Ther 252: 689‐695, 1990.
 527. Wang T, Chan YL. The role of phosphoinositide turnover in mediating the biphasic effect of angiotensin II on renal tubular transport. J Pharmacol Exp Ther 256: 309‐317, 1991.
 528. Wang T, Yang CL, Abbiati T, Schultheis PJ, Shull GE, Giebisch G, Aronson PS. Mechanism of proximal tubule bicarbonate absorption in NHE3 null mice. Am J Physiol 277: F298‐F302, 1999.
 529. Wang X, Armando I, Upadhyay K, Pascua A, Jose PA. The regulation of proximal tubular salt transport in hypertension: An update. Curr Opin Nephrol Hypertens 18: 412‐420, 2009.
 530. Wang Z, Orlowski J, Shull GE. Primary structure and functional expression of a novel gastrointestinal isoform of the rat Na/H exchanger. J Biol Chem 268: 11925‐11928, 1993.
 531. Wang ZQ, Felder RA, Carey RM. Selective inhibition of the renal dopamine subtype D1A receptor induces antinatriuresis in conscious rats. Hypertension 33: 504‐510, 1999.
 532. Weinman EJ, Cunningham R, Shenolikar S. NHERF and regulation of the renal sodium‐hydrogen exchanger NHE3. Pflugers Arch 450: 137‐144, 2005.
 533. Weinman EJ, Cunningham R, Wade JB, Shenolikar S. The role of NHERF‐1 in the regulation of renal proximal tubule sodium‐hydrogen exchanger 3 and sodium‐dependent phosphate cotransporter 2a. J Physiol 567: 27‐32, 2005.
 534. Weinman EJ, Shenolikar S. Regulation of the renal brush border membrane Na+‐H+ exchanger. Annu Rev Physiol 55: 289‐304, 1993.
 535. Weinstein AM. Sodium and chloride transport: Proximal nephron. In: Alpern RJ, Hebert SC, editors. Seldin and Giebisch's The Kidney: Physiology and Pathophysiology. London: Academic Press, 2008.
 536. Wendel M, Knels L, Kummer W, Koch T. Distribution of endothelin receptor subtypes ETA and ETB in the rat kidney. J Histochem Cytochem 54: 1193‐1203, 2006.
 537. Wesson LG. Glomerulotubular balance: History of a name. Kidney Int 4: 236‐238, 1973.
 538. Wesson LG, Jr., Anslow WP, Jr., Smith HW. The excretion of strong electrolytes. Bull N Y Acad Med 24: 586‐606, 1948a.
 539. Wesson LG, Anslow WP, Smith HW. The excretion of strong electrolytes. Bull NY Acad Med 24: 586‐606, 1948b.
 540. Wesson LG, Anslow WP, Jr., Smith HW. The renal excretion of strong electrolytes. Fed Proc 7: 132, 1948c.
 541. Wetzel RK, Sweadner KJ. Immunocytochemical localization of Na‐K‐ATPase alpha‐ and gamma‐subunits in rat kidney. Am J Physiol Renal Physiol 281: F531‐F545, 2001.
 542. Whittembury G, Windhager EE. Electrical potential difference measurements in perfused single proximal tubules of Necturus kidney. J Gen Physiol 44: 679‐687, 1961.
 543. Wiederholt M, Hierholzer K, Windhager EE, Giebisch G. Microperfusion study of fluid reabsorption in proximal tubules of rat kidneys. Am J Physiol 213: 809‐818, 1967.
 544. Wilcox CS, Baylis C, Wingo CS. Glomerular‐tubular balance and proximal regulation. In: Seldin DW, Giebisch G, editors. The Kidney: Physiology and Pathophysiology. New York: Raven Press, 1992.
 545. Wilcox CS, Welch WJ, Schreiner GF, Belardinelli L. Natriuretic and diuretic actions of a highly selective adenosine A1 receptor antagonist. J Am Soc Nephrol 10: 714‐720, 1999.
 546. Wilkes BM, Susin M, Mento PF, Macica CM, Girardi EP, Boss E, Nord EP. Localization of endothelin‐like immunoreactivity in rat kidneys. Am J Physiol 260: F913‐F920, 1991.
 547. Winghager EE. Glomerulo‐tubular balance of sale and water. Physiologist 11: 103‐114, 1968.
 548. Woo AL, Noonan WT, Schultheis PJ, Neumann JC, Manning PA, Lorenz JN, Shull GE. Renal function in NHE3‐deficient mice with transgenic rescue of small intestinal absorptive defect. Am J Physiol Renal Physiol 284: F1190‐F1198, 2003.
 549. Woodhall PB, Tisher CC, Simonton CA, Robinson RR. Relationship between para‐aminohippurate secretion and cellular morphology in rabbit proximal tubules. J Clin Invest 61: 1320‐1329, 1978.
 550. Wright EM. Renal Na(+)‐glucose cotransporters. Am J Physiol Renal Physiol 280: F10‐F18, 2001.
 551. Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev 91: 733‐794, 2011.
 552. Wu MS, Biemesderfer D, Giebisch G, Aronson PS. Role of NHE3 in mediating renal brush border Na+‐H+ exchange. Adaptation to metabolic acidosis. J Biol Chem 271: 32749‐32752, 1996.
 553. Xu H, Chen R, Ghishan FK. Subcloning, localization, and expression of the rat intestinal sodium‐hydrogen exchanger isoform 8. Am J Physiol Gastrointest Liver Physiol 289: G36‐G41, 2005.
 554. Xu J, Li G, Wang P, Velazquez H, Yao X, Li Y, Wu Y, Peixoto A, Crowley S, Desir GV. Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure. J Clin Invest 115: 1275‐1280, 2005.
 555. Yamaguchi I, Jose PA, Mouradian MM, Canessa LM, Monsma FJ, Jr., Sibley DR, Takeyasu K, Felder RA. Expression of dopamine D1A receptor gene in proximal tubule of rat kidneys. Am J Physiol 264: F280‐F285, 1993.
 556. Yamamoto T, Suzuki H, Kubo Y, Matsumoto A, Uemura H. Endothelin A receptor‐like immunoreactivity on the basal infoldings of rat renal tubules and collecting ducts. Arch Histol Cytol 71: 77‐87, 2008.
 557. Yamamoto T, Uemura H. Distribution of endothelin‐B receptor‐like immunoreactivity in rat brain, kidney, and pancreas. J Cardiovasc Pharmacol 31 (Suppl 1): S207‐S211, 1998.
 558. Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332: 411‐415, 1988.
 559. Yingst DR, Araghi A, Doci TM, Mattingly R, Beierwaltes WH. Decreased renal perfusion rapidly increases plasma membrane Na‐K‐ATPase in rat cortex by an angiotensin II‐dependent mechanism. Am J Physiol Renal Physiol 297: F1324‐F1329, 2009.
 560. Yingst DR, Massey KJ, Rossi NF, Mohanty MJ, Mattingly RR. Angiotensin II directly stimulates activity and alters the phosphorylation of Na‐K‐ATPase in rat proximal tubule with a rapid time course. Am J Physiol Renal Physiol 287: F713‐F721, 2004.
 561. Yingst DR, Polasek PM. Sensitivity and reversibility of Ca‐dependent inhibition of the (Na+‐K+)‐ATPase of human red blood cells. Biochim Biophys Acta 813: 282‐286, 1985.
 562. You G, Lee WS, Barros EJ, Kanai Y, Huo TL, Khawaja S, Wells RG, Nigam SK, Hediger MA. Molecular characteristics of Na(+)‐coupled glucose transporters in adult and embryonic rat kidney. J Biol Chem 270: 29365‐29371, 1995.
 563. Yu C, Yang Z, Ren H, Zhang Y, Han Y, He D, Lu Q, Wang X, Wang X, Yang C, Asico LD, Hopfer U, Eisner GM, Jose PA, Zeng C. D3 dopamine receptor regulation of ETB receptors in renal proximal tubule cells from WKY and SHRs. Am J Hypertens 22: 877‐883, 2009.
 564. Yu P, Asico LD, Luo Y, Andrews P, Eisner GM, Hopfer U, Felder RA, Jose PA. D1 dopamine receptor hyperphosphorylation in renal proximal tubules in hypertension. Kidney Int 70: 1072‐1079, 2006.
 565. Yun CH, Tse CM, Nath SK, Levine SA, Brant SR, Donowitz M. Mammalian Na+/H+ exchanger gene family: Structure and function studies. Am J Physiol 269: G1‐11, 1995.
 566. Zeidel ML, Seifter JL, Lear S, Brenner BM, Silva P. Atrial peptides inhibit oxygen consumption in kidney medullary collecting duct cells. Am J Physiol 251: F379‐F383, 1986.
 567. Zeng C, Asico LD, Wang X, Hopfer U, Eisner GM, Felder RA, Jose PA. Angiotensin II regulation of AT1 and D3 dopamine receptors in renal proximal tubule cells of SHR. Hypertension 41: 724‐729, 2003.
 568. Zeng C, Jose PA. Dopamine receptors: Important antihypertensive counterbalance against hypertensive factors. Hypertension 57: 11‐17, 2011.
 569. Zeng C, Liu Y, Wang Z, He D, Huang L, Yu P, Zheng S, Jones JE, Asico LD, Hopfer U, Eisner GM, Felder RA, Jose PA. Activation of D3 dopamine receptor decreases angiotensin II type 1 receptor expression in rat renal proximal tubule cells. Circ Res 99: 494‐500, 2006.
 570. Zeng C, Zhang M, Asico LD, Eisner GM, Jose PA. The dopaminergic system in hypertension. Clin Sci (Lond) 112: 583‐597, 2007.
 571. Zhang J, Ren C, Chen L, Navedo MF, Antos LK, Kinsey SP, Iwamoto T, Philipson KD, Kotlikoff MI, Santana LF, Wier WG, Matteson DR, Blaustein MP. Knockout of Na+/Ca2+ exchanger in smooth muscle attenuates vasoconstriction and L‐type Ca2+ channel current and lowers blood pressure. Am J Physiol Heart Circ Physiol 298: H1472‐H1483, 2010.
 572. Zhao D, Zhang J, Blaustein MP, Navar LG. Attenuated renal vascular responses to acute angiotensin II infusion in smooth muscle specific Na+/Ca2+ exchanger knockout mice. Am J Physiol Renal Physiol 301 (3): F574‐9, 2011.
 573. Zhou Y, Bouyer P, Boron WF. Role of the AT1A receptor in the CO2− induced stimulation of HCO3− reabsorption by renal proximal tubules. Am J Physiol Renal Physiol 293: F110‐F120, 2007.
 574. Zhu Y, Wang DH. Segmental regulation of sodium and water excretion by TRPV1 activation in the kidney. J Cardiovasc Pharmacol 51: 437‐442, 2008.
 575. Zhuo JL, Alcorn D, Harris PJ, Mendelsohn FA. Localization and properties of angiotensin II receptors in rat kidney. Kidney Int Suppl 42: S40‐S46, 1993.
 576. Zhuo JL, Allen AM, Alcorn D, MacGregor D, Aldred GP, Mendelsohn FA. The distribution of angiotensin II receptors. In: Laragh JH, Brenner BM, editors. Hypertension: Pathology, Diagnosis & Management. 1(2nd Ed.). New York: Raven Press, 1995, pp. 1739‐1762.
 577. Zhuo JL, Dean R, MacGregor D, Alcorn D, Mendelsohn FA. Presence of angiotensin II AT2 receptor binding sites in the adventitia of human kidney vasculature. Clin Exp Pharmacol Physiol Suppl 3: S147‐S154, 1996.
 578. Zhuo JL, Dean R, Maric C, Alcorn D, Harris P, Mendelsohn FA. Localization and roles of angiotensin, endothelin and bradykinin receptors in interstitial cells of the renal medulla. Ulfendahl, H. and Aurell, M, editors. Wenner‐Gren Foundation International Symposium: Renin‐Angiotensin, 221‐235, 1998.
 579. Zhuo JL, Dean R, Maric C, Aldred PG, Harris P, Alcorn D, Mendelsohn FA. Localization and interactions of vasoactive peptide receptors in renomedullary interstitial cells of the kidney. Kidney Int Suppl 67: S22‐S28, 1998.
 580. Zhuo JL, Harris PJ, Skinner SL. Modulation of proximal tubular reabsorption by angiotensin II. Clin Exp Pharmacol Physiol 13: 277‐281, 1986.
 581. Zhuo JL, Mendelsohn FA. Intrarenal Angiotensin II Receptors. In: Robertson JIS, Nicholls MG, editors. The Renin‐Angiotensin System: Biochemistry, Pathophysiology and Therapeutics. London & New York: Gower Medical Publishing, 1993, 1, pp. 25.1‐25.14.
 582. Zhuo JL, Moeller I, Jenkins T, Chai SY, Allen AM, Ohishi M, Mendelsohn FA. Mapping tissue angiotensin‐converting enzyme and angiotensin AT1, AT2 and AT4 receptors. J Hypertens 16: 2027‐2037, 1998.
 583. Zhuo JL, Song K, Chai SY, Mendelsohn FA. Anatomical localization of components of the renin‐angiotensin system in different organs and tissues. In: MacGregor GA, Sever PS, editors. Inhibition of the Renin‐Angiotensin System: Recent Advances. Hong Kong: Gardiner‐Calwell Communications (Pacific) Ltd., 1993, pp. 17‐25.
 584. Zhuo JL, Song K, Harris PJ, Mendelsohn FA. In vitro autoradiography reveals predominantly AT1 angiotensin II receptors in rat kidney. Ren Physiol Biochem 15: 231‐239, 1992.
 585. Zhuo JL, Thomas D, Harris PJ, Skinner SL. The role of endogenous angiotensin II in the regulation of renal haemodynamics and proximal fluid reabsorption in the rat. J Physiol 453: 1‐13, 1992.
 586. Zhuo JL. Renomedullary interstitial cells: A target for endocrine and paracrine actions of vasoactive peptides in the renal medulla. Clin Exp Pharmacol Physiol 27: 465‐473, 2000.
 587. Zhuo JL, Harris PJ, Skinner SL. Atrial natriuretic factor modulates proximal glomerulotubular balance in anesthetized rats. Hypertension 14: 666‐673, 1989.
 588. Zhuo JL, Li XC. Novel roles of intracrine angiotensin II and signalling mechanisms in kidney cells. J Renin Angiotensin Aldosterone Syst 8: 23‐33, 2007.
 589. Zhuo JL, Li XC. New insights and perspectives on intrarenal renin‐angiotensin system: Focus on intracrine/intracellular angiotensin II. Peptides 32: 1551‐1565, 2011.
 590. Zhuo JL, Li XC, Garvin JL, Navar LG, Carretero OA. Intracellular angiotensin II induces cytosolic Ca2+ mobilization by stimulating intracellular AT1 receptors in proximal tubule cells. Am J Physiol Renal Physiol 290: F1382‐F1390. 2006.
 591. Zimanyi MA, Hoy WE, Douglas‐Denton RN, Hughson MD, Holden LM, Bertram JF. Nephron number and individual glomerular volumes in male Caucasian and African American subjects. Nephrol Dial Transplant 24: 2428‐2433, 2009.
 592. Zimmerman RS, Schirger JA, Edwards BS, Schwab TR, Heublein DM, Burnett JC, Jr. Cardio‐renal‐endocrine dynamics during stepwise infusion of physiologic and pharmacologic concentrations of atrial natriuretic factor in the dog. Circ Res 61: 63‐69, 1987.

Related Articles:

Atrial Natriuretic Factor
Biochemical Characterization of Individual Nephron Segments
Dopamine and Renal Function and Blood Pressure Regulation
Functional Ultrastructure of the Proximal Tubule
Glucose Transport in the Renal Proximal Tubule
Hypertension: Physiology and Pathophysiology
Mechanisms of Fluid Transport Across Renal Tubules
Natriuretic Peptides
Nephron Heterogeneity
Principles of Electrolyte Transport Across Plasma Membranes of Renal Tubular Cells
Structure and Function of the Thin Limbs of the Loop of Henle
Renal Acidification: Integrated Tubular Responses
Micropuncture of the Kidney: A Primer on Techniques
Renal Micropuncture Techniques
Renin–Angiotensin–Aldosterone System and the Renal Regulation of Sodium, Potassium, and Blood Pressure Homeostasis
A Standard Nomenclature for Structures of the Kidney
Tubular Transport of Amino Acids and Small Peptides
Chronic Blood Pressure Control

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Proximal Nephron
 

How to Cite

Jia L. Zhuo, Xiao C. Li. Proximal Nephron. Compr Physiol 2013, 3: 1079-1123. doi: 10.1002/cphy.c110061