Hydraulic and colloid osmotic pressure profiles along idealized glomerular capillaries in hydropenic and euvolemic rats. Values shown are mean values from studies listed in Tables 2 and 3. ΔP = P_GC‐P_T and ΔΠ = Π_GC‐Π_T, where P_GC and P_T are hydraulic pressures in glomerular capillary and Bowman's space, respectively, and Π_GC and Π_T are corresponding colloid osmotic pressures. Because Π_T is negligible, ΔΠ essentially equals Π_GC P_UF is the ultrafiltration pressure at any point. Area between ΔP and ΔΠ curves represents net ultrafiltration pressure, (P_UF). Curves A and B in left panel represent two of many possible ΔΠ profiles under conditions of filtration pressure equilibrium. Curve D, disequilibrium; line C, hypothetical linear ΔΠ profile; Q_A, glomerular plasma flow ra])G SNGFR, single nephron glomerular filtration rate.

Relationship between glomerular capillary ultrafiltration coefficient(K_f) and body weight in rats. Each point represents mean values obtained from one study. Open squares and open circles indicate data obtained from Munich‐Wistar rats and include only those studies in which animals were at or near filtration pressure disequilibrium [euvolemic or plasma‐expanded male or male plus female rats from Tables 3 and 4, (squares) or hydropenic and euvolemic female rats at disequilibrium from Tables 2 and 3 (circles)]. Thus K_f values are unique rather than miminum estimates. Open triangle, study in hydropenic Holtzman rats at equilibrium and thus is minimum value 39. Solid line, representing open symbols, is given by equation y = 0.021(x) −0.47 (r = 0.67). Filled squares, values obtained in euvolemic Munich‐Wistar rats fasted for 12–24 h (Table 3). All other filled symbols were obtained in species without surface glomeruli and hence relied on stop‐flow pressure measurements to estimate (P_GC). Included are data from Sprague‐Dawley rats (filled circles) spontaneous hypertensive rats (half‐filled circles), and Wistar‐Kyoto rats (filled triangles) from Table 8. Dashed line, denoting best fit to filled symbols, is given by equation y = 0.0074(x) + 0.25 (r = 0.80, P<0.01 vs. solid line).

Relationships of single nephron glomerular filtration rate (SNGFR) and single nephron filtration fraction (SNFF) to isolated changes in glomerular plasma flow rate. Because SNGFR and SNFF can also be affected by changes in 〈ΔP〉, K_f, or Π_A, only studies in which 〈ΔP〉 = 35–40 mm Hg, minimum K_f ≥ 3 nl/min · mm Hg, and Π;_A≅18–20 mm Hg are included. Included are studies from Tables 2–4 as well as studies under a variety of physiological conditions that fell within these limits 117,349,353,355,362,659,660,661,694. Solid lines denote model predictions based on mean values of 〈ΔP〉, K_f, and Π_A observed in these studies [〈ΔP〉 = 36.4 mm Hg, Π_A = 18.8 mm Hg, and K_f = 4.9 nl/(min · mm Hg)].

Relationship between single nephron glomerular filtration rate (SNGFR) and glomerular plasma flow rate. Each point represents mean values obtained in one study. Open circles, Munich‐Wistar rats presented in Tables 2–4; closed triangles, Wistar‐Kyoto rats; open triangles, Holtzman tats; closed circles, spontaneous hypertensive rats presented in Table 8; open squares, Sprague‐Dawley rats (presented in Table 8 (and refs. 138,208,209,472); closed squares, dogs presented in Table 7; half‐closed circles, calculated values of SNGFR and glomerular plasma flow rate in humans based on dividing GFR and renal plasma flow by 1 million (the total number of nephrons) for a variety of studies (see Fig. 5).

Relationship between whole‐kidney glomerular filtration rate (GFR) and renal plasma flow rate in dogs (values expressed per kidney) and humans [values shown for one kidney and expressed as ml/(min · 1.73 m²)]. Human data: closed circles, studies conducted following a low‐protein meal 608, on alternate‐day protein feeding 346, or following overnight fast (82, 112, 641. Administration of a protein meal (open circles or half‐closed circles) resulted in increased GFR and renal plasma flow in three studies 130,346,608. Lines connect values in same study. Closed squares, no information given regarding diets 167,626,793; open square, cardiac failure patients 166. Dog studies: open triangles, variations in GFR and renal plasma flow resulted primarily from variations in renal perfusion pressure, including either normal 99,156,316,338,384,479,551,556,568,567,570,738,771 or reduced 156,527,567,738 arterial pressures; closed triangles, values obtained following hyperoncotic plasma expansion 403; response to a saline load 338.

Relationship of single nephron glomerular filtration rate (SNGFR) and single nephron filtration fraction (SNFF) to variations in the transcapillary hydraulic pressure gradient ((ΔP)). Each point denotes mean value from one study. To minimize variations in SNGFR and SNFF caused by differences in Π_A and K_f, all studies selected had Π_A values between 16 and 20 mm Hg and had normal values of K_f ≥ 3 nl/(min · mm Hg). Data are compared at two selected ranges of glomerular plasma flow rate (Q_A) (130–170 nl/min; mean, 147 ± 2 nl/min or 40–70 nl/min; mean, 60 ± 3 nl/min) in which a relatively wide range of 〈ΔP〉 values were obtained. Low Q_A data were from several studies 140,405,515,622,659. High Q_A data include all studies listed in Tables 3 and 4 that meet guidelines as well as other studies 349,355,356,362,515,659,660. Dashed lines, model predictions for low Q_A studies using mean values of (17 mm Hg) and Q_A (60 nl/min) obtained in these studies, together with mean (unique) value of K_f in high Q_A experiments, assuming that variations in Q_A per se do not alter K_f 231; solid lines, model predictions for high Q_A data from rats using mean values of Π_A (18 mm Hg), Q_A (147 nl/min), and K_f [5.4 nl/(min · mm Hg)] obtained in these studies.

Effects of selective alterations in K_f on single nephron glomerular filtration rate (SNGFR) and single nephron filtration fraction (SNFF). Only studies in which a unique value of K_f was obtained (i.e., Π_E/〈ΔP〉 ≤ 0.95) are included. Data are shown for two ranges of Q_A: open circles, 90–125 nl/min (mean, Q_A = 100nl/min); and closed circles, 150–180 nl/min (mean, Q_A≅ 170 nl/min). For low Q_A studies, Π_A was limited to 16–20 mm Hg and 〈ΔP〉 from 36 to 42 mm Hg. High flow studies had similar ranges of Π_A (17–22 mm Hg) and 〈ΔP〉 (36–43 mm Hg). Model predictions shown by dashed lines are for low Q_A values (data from refs. 27,75,238,349,352,469,548,584,659,660,708,756); solid lines represent predictions for high Q_A values (data from refs. 77,231,236,353,355,358,585,586,758,805).

Theoretical relationships between plasma oncotic pressure (Π_A) and both single nephron glomerular filtration rate (SNGFR) and single nephron filtration fraction (SNFF). Dashed line, model predictions for euvolemic Munich‐Wistar rats based on values of Q_A, 〈ΔP〉, and K_f of 151 nl/min, 35 mm Hg, and 5.6 nl/(min · mm Hg), respectively (Table 3); solid line, hydropenia in which Q_A and 〈ΔP〉 were 79 nl/min and 34 mm Hg (Table 2), respectively. Because only a minimum value of K_f can be determined in hydropenic rats (Π_E = 〈ΔP〉, Table 2), the unique value of 5.6 nl/min · mm Hg determined in euvolemic rats was used.

Relationship between K_f and plasma protein concentration (C_A). Closed circles, mean values (± S.E.M.) obtained by Baylis et al. 77 under a variety of conditions, with and without volume expansion, designed to alter C_A; closed square, a study in which an isovolemic reduction in hematocrit produced filtration pressure disequilibrium without volume expansion 515; closed triangles, values obtained in rats with isoncotic plasma volume expansion in which Q_A was varied by altering renal perfusion pressure by aortic constriction or carotid occlusion 231.

Hydraulic pressure profile in rat kidney. Open circles, values obtained in studies of euvolemic Munich‐Wistar rats (Table 3); closed circles, studies of hydropenic rats (Table 2); closed triangles, values obtained by Casellas and Navar 171 in Sprague‐Dawley rats in unique population of juxtamedullary nephrons at inside cortical surface apposed to pelvic lining and arcuate veins. Hydraulic pressures can be obtained in proximal (Early a.a.) and distal (Late a.a.) portions of afferent arteriole and in proximal (Early e.a.) and distal (Late e.a.) segments of efferent arteriole, and in peritubular capillaries (P_c), interlobular veins (I.V.), and renal vein (R.V.). For micropuncture experiments, systemic arterial pressure () averaged — 110 mm Hg, whereas in study of Casellas and Navar 171 arcuate artery (Arc. Art.) was perfused with whole blood at 96 mm Hg. , hydraulic pressure in glomerular capillaries.

Pathways of renin synthesis and processing in mouse submaxillary gland. A: proposed sites of cleavage (upward arrows) and M_rs of each compound (far right column). B: synthesis, packaging into granules, and secretion of renin.

Cellular control of renin release. Occupancy of adenylate cyclase (AC)‐linked receptors by agonists [norepinephrine (NE), histamine (H), and prostaglandins (PG)] results in stimulation of cAMP production and phosphorylation of intermediate protein kinase (PK) that stimulates (+) renin secretion. N, guanine nucleotide regulatory proteins specific for each agonist. Though not shown, angiotensin II (AΠ) and vasopressin (AVP) also act through N (or G) proteins to increase calcium influx as well as calcium release from intracellular storage sites. Membrane depolarization (Dep.) can also increase Ca²⁺ influx through voltage‐sensitive channels. Increased [Ca²⁺], leads to formation of the calcium‐calmodulin (Ca‐CM) complex that inhibits (−) renin release. Decreases in [Ca²⁺]_i uncouples the Ca‐CM complex, thus de‐inhibiting renin release. R_AΠ, R_avp, R_H2, R_β. and R_PG; receptors for angiotensin II, arginine vasopressin, histamine (H₂‐type), norepinephrine (β‐type), and prostaglandins, respectively.

Effects of intravenous infusion of angiotensin II (200–600 ng/kg/min) determinants of glomerular ultrafiltration in Munich‐Wistar rat. Left, data obtained when renal perfusion pressure () was allowed to increase; right, results obtained when increase in was prevented. Data are means ± S.E. SNGFR, single nephron glomerular filtration rate.

Role of angiotensin II in mediating altered renal function of congestive heart failure induced by myocardial infarction (M.I.). Control euvolemic sham‐operated rats were studied during two periods; before (open circles) and during (filled circles) infusion of angiotensin I‐converting enzyme inhibitor teprotide [SQ20881; 359,363]. SNGFR, single nephron glomerular filtration ra])G SNFF, single nephron filtration fracti])R , renal perfusion pressure.

Mechanism of action of angiotensin II (AT II) in contraction of renal vasculature and glomerular mesangial cells. R, receptor; G_αβγ, guanine nucleotide‐binding regulatory protein with its three subunits, α, β, and γ; GTP, guanine trisphospha])G PLC, phospholipase C; PlP₂, phosphatidylinositol‐4,5‐bisphospha])G IP₃, inositol‐1,4,5‐trisphospha])G DAG, 1,2‐diacylglycerol; Ca²⁺, intracellular free calcium; PKC, protein kinase C; LC, lipocortin; PLA₂, phospholipase A₂; PL, membrane phospholipids; AA, arachidonic acid; PGE₂, prostaglandin E₂; cAMP, cyclic adenosine monophospha])G cAMP‐PK, cAMP‐dependent protein kinase; MLCK, myosin light chain kinase; P‐MLCK, phosphorylated MLCK; MLCK‐CAM, MLCK‐calcium‐calmodulin active complex; P_i, phospha])G *, activated form of enzyme. Parts A, B, and C in upper panel show sequence of events leading from occupancy of the receptor to activation of PLC. Lower panel shows sequence of events occurring in cells after PLC activation.

Lipoxygenase pathway for biosynthesis of vasoactive leukotrienes and cyclooxygenase pathway for synthesis and degradation of prostaglandins, prostacyclin, and thromboxane A₂ (T_xA₂).

Effects of PGE₂, PGI₂, and dibutyryl (DB)‐cAMP on the determinants of glomerular filtration in rat. Data include effects on single nephron glomerular filtration rate (SNGFR), panel A; glomerular plasma flow rate (Q_A), panel B; mean glomerular capillary hydraulic pressure (), panel C; glomerular ultrafiltration coefficient (K_f), panel D; and sum of the pre‐ and postglomerular resistances (R_TA), panel E. Euvolemic control animals were infused with cyclooxygenase inhibitors meclofenamate (Meclo.) or indomethacin (Indo.) or a cyclooxygenase inhibitor plus angiotensin II competitive antagonist saralasin. Effects of PGE₂, PGI₂, and DB‐cAMP were first examined during inhibition of endogenous prostaglandin production by Indo. or Meclo. and then with the added inhibition of endogenous angiotensin II by saralasin.

Effects of reduced mean arterial pressure on the measured determinants of glomerular ultrafiltration in hydropenic rats (A) and in mildly plasma‐expanded Munich‐Wistar rats before (B) and during (C) the administration of smooth muscle relaxant papaverine. Data (from ref. 228 and 622) are shown as means ± 1 S.E.

Filtrate‐to‐plasma concentration ratio (θ) as function of molecular size for dextran sulfate (DS), neutral dextran (D), and diethylaminoethyl dextran (DEAE). Symbols, mean values ± S.E. measured by Bohrer et al. 120,122 in normal hydropenic Munich‐Wistar rats; curves are theoretical calculations based on values of Q_A, 〈ΔP〉, and C_A reported in those studies with K_f = 4.8 nl/(min · mm Hg), r_o = 47 Å, and C_m= 165 mEq/liter.

Schematic of macromolecular solute (represented as sphere of radius, r_s) moving through membrane pore (of radius r_o and length l). λ = r_s/r_o.

Hindrance factors for convection (W) and diffusion (H) based on hydrodynamic theory for movement of uncharged spherical molecules in cylindrical pores.

Filtrate‐to‐plasma concentration ratio (θ) as function of molecular charge (z) molecular radius (r_s). Results are shown for two values of membrane fixed charge concentration (C_m). Other inputs were Q_A = 75 nl/min, 〈ΔP> = 35 mm Hg, C_A = 5.7 g/dl, K_f = 4.8 nl/(min · mm Hg), and r_o = 50 Å, all representative of the normal hydropenic Munich‐Wistar rat.

Filtrate‐to‐plasma concentration ratio (θ) for serum albumin as function of membrane fixed charge concentration (C_m) and effective molecular charge (z). Other inputs were Q_A = 75 nl/min, 〈ΔP〉 = 35 mm Hg, C_A = 5.7 g/dl, K_f = 4.8 nl/(min · mm Hg), and r_o = 50 Å, all representative of the normal hydropenic Munich‐Wistar rat.

Relationship between filtrate‐to‐plasma concentration ratio (θ), effective molecular charge (z), and glomerular plasma flow rate (Q_A). Calculations assumed C_m = 165 mEq/liter, r_s = 30 Å, 〈ΔP〉 = 35 mm Hg, C_A, = 5.7g/dl, K_f = 4.8 nl/‐(min · mm Hg), and r_o = 50 Å, all representative of the normal hydropenic Munich‐Wistar rat.

Relationship between filtrate‐to‐plasma concentration ratio (θ), effective molecular charge (z), and transmembrane hydraulic pressure difference 〈ΔP〉. Input quantities were C_m=165 mEq/liter, r_s = 30Å, Q_A = 75 nl/min, C_A = 5.7g/dl, K_f = 4.8 nl/min · mm Hg), and r_o = 50Å.

Relationship between filtrate‐to‐plasma concentration ratio (θ), effective molecular charge (z), and ultrafiltration coefficient(K_f). Effective pore radius is assumed to remain constant. Input quantities were C_m=165 mEq/liter, r_s = 30 Å, Q_A = 75 nl/min, 〈ΔP〉 = 35 mm Hg, C_A = 5.7g/dl, and r_o = 50 A.