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Physiology of Endothelin and the Kidney

Donald E. Kohan, Edward W. Inscho, Donald Wesson, David M. Pollock

10.1002/cphy.c100039

Source: Volume 1, Issue 2, April 2011

Published online: April 2011

Full Article on Wiley Online Library



Abstract

Since its discovery in 1988 as an endothelial cell‐derived peptide that exerts the most potent vasoconstriction of any known endogenous compound, endothelin (ET) has emerged as an important regulator of renal physiology and pathophysiology. This review focuses on how the ET system impacts renal function in health; it is apparent that ET regulates multiple aspects of kidney function. These include modulation of glomerular filtration rate and renal blood flow, control of renin release, and regulation of transport of sodium, water, protons, and bicarbonate. These effects are exerted through ET interactions with almost every cell type in the kidney, including mesangial cells, podocytes, endothelium, vascular smooth muscle, every section of the nephron, and renal nerves. In addition, while not the subject of the current review, ET can also indirectly affect renal function through modulation of extrarenal systems, including the vasculature, nervous system, adrenal gland, circulating hormones, and the heart. As will become apparent, these pleiotropic effects of ET are of fundamental physiologic importance in the control of renal function in health. In addition, to help put these effects into perspective, we will also discuss, albeit to a relatively limited extent, how alterations in the ET system can contribute to hypertension and kidney disease. © 2011 American Physiological Society. Compr Physiol 1:883‐919, 2011.

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Figure 1. Figure 1.

Biosynthetic and degradation pathways for endothelin‐1 (ET‐1). ET‐1 mRNA encodes preproET‐1. The short signal peptide is cleaved to yield proET‐1 which, in turn, is cleaved by furin or PC7 convertases at dibasic amino acids to yield Big ET‐1. Big ET‐1 is cleaved by different ET‐converting enzymes (ECE) to mature ET‐1. ET‐1 is degraded by neutral endopeptidase and deamidase.
Figure 2. Figure 2.

Schema of ET in vasculature. Endothelial cells express ETB exclusively and are the predominant vascular source of ET‐1. ET‐1 and nitric oxide synthase 3 (NOS3) can increase ETB activity or amount, respectively, leading to NO and PGE2 production with resulting vasolaxation. Activation of vascular smooth muscle ETA or ETB leads to a signaling cascade involving G‐proteins, phospholipase C (PLC) and inositol triphosphate (IP3) that activate voltage‐operated Ca2+ channel (VOC) and sarcoplasmic reticulum (SR)‐mediated increases in [Ca2+]i and calmodulin (CaM) activation. CaM, together with activation of protein kinase C (PKC) by diacylglycerol (DAG) and Ras/Raf/ERK1/2 activation, causes myosin light chain kinase (MLCK) activation and cell contraction.
Figure 3. Figure 3.

Schema of functional ET receptors in the glomerulus and renal arterioles (Panel A), nephron (Panel B) and vasa recta (Panel C). A = contractile ETA; B = contractile ETB; white B with shadow: relaxant or natriuretic ETB that stimulates NO production; white A with shadow: natriuretic ETA. The amount of ET receptor shown in a given area is representative of the level of ET receptor activity in that region. Afferent arteriolar smooth muscle has more vasoconstrictive ET receptors than do efferent arterioles, while efferent arteriole endothelium has more vasodilatory ETB than does afferent arteriole (Panel A). Podocytes and mesangial cells contain primarily contractile ETA (Panel A). The inner medullary collecting duct (IMCD) has the greatest density of natriuretic ET receptors, although natriuretic ET receptors exist in the cortical collecting duct (CCD), thick ascending limb (TAL) and proximal tubule (PT) (Panel B). Vasa recta express contractile ETA on pericytes and vasodilatory ETB on endothelial cells (Panel C).
Figure 4. Figure 4.

Synthesis and actions of ET‐1 in mesangial cells. A large variety of substances stimulate ET‐1 production, including ET‐1 itself. Vasodilators tend to inhibit mesangial cell ET‐1 synthesis. ET‐1 likely acts in an autocrine manner. In general, ETA activation leads to cell contraction, while ETB activation causes relaxation. Please see text for definitions of abbreviations.
Figure 5. Figure 5.

Synthesis and actions of ET‐1 in the proximal tubule. ET‐1 production is enhanced during inflammation, hypoxia, glomerular injury, and acidemia. Most studies implicate ETB in mediating ET effects on the proximal tubule, although ETA activation may result in inhibition of Na reabsorption. ETB effects appear to depend upon the concentration of ET‐1, with lower concentrations stimulating Na transport processes and higher concentrations having the opposite effect. It is likely that ET‐1 exerts primary a natriuretic effect on the proximal tubule under physiologic conditions. Please see text for definitions of abbreviations.
Figure 6. Figure 6.

Synthesis and actions of ET‐1 in the thick ascending limb. ET‐1 production is stimulated by increased medullary osmolality which occurs during high Na intake. ET‐1 can then act in an autocrine manner, via ETB, to stimulate NOS3 activity and inhibit NKCC2. ETB may also increased 20‐HETE with possible inhibition of Na/K ATPase activity, although this is unproven. Please see text for definitions of abbreviations.
Figure 7. Figure 7.

Synthesis and actions of ET‐1 in the collecting duct (CD). ET‐1 gene transcription is under complex control, involving transactivators binding to cis elements in the ET‐1 promoter, as well as histone methylation. The latter effect mediates aldosterone stimulation of CD ET‐1 production; this may serve as a negative feedback regulator of aldosterone‐stimulated Na transport in this nephron segment. ETB mediates ET‐1 inhibition of water transport, primarily through inhibition of AVP‐stimulated adenylyl cyclase (AC) activity. ETB also mediates ET‐1 inhibition of ENaC activity; this involves both NO and MAPK. V2 and AT1 receptors have been reported to inhibit ETB expression in this nephron segment. The role of ETA in regulating CD Na and water transport is uncertain. Please see text for definitions of abbreviations.
Figure 8. Figure 8.

Role of the renal ET system in control of urinary acid excretion. Dietary acid intake stimulates renal and possibly adrenal ET‐1 production. Renal ET‐1 increases proximal tubule H+ secretion and distal nephron H+ secretion and bicarbonate reabsorption. Adrenal ET‐1 increases aldosterone that stimulates distal nephron H+ secretion. Please see text for definitions of abbreviations.
Figure 9. Figure 9.

Integrated renal response to high Na intake. High Na intake increases renal ET‐1 synthesis, particularly in the nephron. This can reduced tubule Na reabsorption by inhibiting Na transport mechanisms in the proximal tubule, thick ascending limb (TAL) and collecting duct (CD). ET‐1, most likely derived from the medullary CD and/or medullary TAL, may also increase medullary blood flow through vasodilation of vasa recta.


Figure 1.

Biosynthetic and degradation pathways for endothelin‐1 (ET‐1). ET‐1 mRNA encodes preproET‐1. The short signal peptide is cleaved to yield proET‐1 which, in turn, is cleaved by furin or PC7 convertases at dibasic amino acids to yield Big ET‐1. Big ET‐1 is cleaved by different ET‐converting enzymes (ECE) to mature ET‐1. ET‐1 is degraded by neutral endopeptidase and deamidase.



Figure 2.

Schema of ET in vasculature. Endothelial cells express ETB exclusively and are the predominant vascular source of ET‐1. ET‐1 and nitric oxide synthase 3 (NOS3) can increase ETB activity or amount, respectively, leading to NO and PGE2 production with resulting vasolaxation. Activation of vascular smooth muscle ETA or ETB leads to a signaling cascade involving G‐proteins, phospholipase C (PLC) and inositol triphosphate (IP3) that activate voltage‐operated Ca2+ channel (VOC) and sarcoplasmic reticulum (SR)‐mediated increases in [Ca2+]i and calmodulin (CaM) activation. CaM, together with activation of protein kinase C (PKC) by diacylglycerol (DAG) and Ras/Raf/ERK1/2 activation, causes myosin light chain kinase (MLCK) activation and cell contraction.



Figure 3.

Schema of functional ET receptors in the glomerulus and renal arterioles (Panel A), nephron (Panel B) and vasa recta (Panel C). A = contractile ETA; B = contractile ETB; white B with shadow: relaxant or natriuretic ETB that stimulates NO production; white A with shadow: natriuretic ETA. The amount of ET receptor shown in a given area is representative of the level of ET receptor activity in that region. Afferent arteriolar smooth muscle has more vasoconstrictive ET receptors than do efferent arterioles, while efferent arteriole endothelium has more vasodilatory ETB than does afferent arteriole (Panel A). Podocytes and mesangial cells contain primarily contractile ETA (Panel A). The inner medullary collecting duct (IMCD) has the greatest density of natriuretic ET receptors, although natriuretic ET receptors exist in the cortical collecting duct (CCD), thick ascending limb (TAL) and proximal tubule (PT) (Panel B). Vasa recta express contractile ETA on pericytes and vasodilatory ETB on endothelial cells (Panel C).



Figure 4.

Synthesis and actions of ET‐1 in mesangial cells. A large variety of substances stimulate ET‐1 production, including ET‐1 itself. Vasodilators tend to inhibit mesangial cell ET‐1 synthesis. ET‐1 likely acts in an autocrine manner. In general, ETA activation leads to cell contraction, while ETB activation causes relaxation. Please see text for definitions of abbreviations.



Figure 5.

Synthesis and actions of ET‐1 in the proximal tubule. ET‐1 production is enhanced during inflammation, hypoxia, glomerular injury, and acidemia. Most studies implicate ETB in mediating ET effects on the proximal tubule, although ETA activation may result in inhibition of Na reabsorption. ETB effects appear to depend upon the concentration of ET‐1, with lower concentrations stimulating Na transport processes and higher concentrations having the opposite effect. It is likely that ET‐1 exerts primary a natriuretic effect on the proximal tubule under physiologic conditions. Please see text for definitions of abbreviations.



Figure 6.

Synthesis and actions of ET‐1 in the thick ascending limb. ET‐1 production is stimulated by increased medullary osmolality which occurs during high Na intake. ET‐1 can then act in an autocrine manner, via ETB, to stimulate NOS3 activity and inhibit NKCC2. ETB may also increased 20‐HETE with possible inhibition of Na/K ATPase activity, although this is unproven. Please see text for definitions of abbreviations.



Figure 7.

Synthesis and actions of ET‐1 in the collecting duct (CD). ET‐1 gene transcription is under complex control, involving transactivators binding to cis elements in the ET‐1 promoter, as well as histone methylation. The latter effect mediates aldosterone stimulation of CD ET‐1 production; this may serve as a negative feedback regulator of aldosterone‐stimulated Na transport in this nephron segment. ETB mediates ET‐1 inhibition of water transport, primarily through inhibition of AVP‐stimulated adenylyl cyclase (AC) activity. ETB also mediates ET‐1 inhibition of ENaC activity; this involves both NO and MAPK. V2 and AT1 receptors have been reported to inhibit ETB expression in this nephron segment. The role of ETA in regulating CD Na and water transport is uncertain. Please see text for definitions of abbreviations.



Figure 8.

Role of the renal ET system in control of urinary acid excretion. Dietary acid intake stimulates renal and possibly adrenal ET‐1 production. Renal ET‐1 increases proximal tubule H+ secretion and distal nephron H+ secretion and bicarbonate reabsorption. Adrenal ET‐1 increases aldosterone that stimulates distal nephron H+ secretion. Please see text for definitions of abbreviations.



Figure 9.

Integrated renal response to high Na intake. High Na intake increases renal ET‐1 synthesis, particularly in the nephron. This can reduced tubule Na reabsorption by inhibiting Na transport mechanisms in the proximal tubule, thick ascending limb (TAL) and collecting duct (CD). ET‐1, most likely derived from the medullary CD and/or medullary TAL, may also increase medullary blood flow through vasodilation of vasa recta.

References
 1. Abassi Z, Ellahham S, Winaver J, Hoffman A. The intrarenal endothelin system and hypertension. News Physiol Sci 16: 152–156, 2001.
 2. Abassi ZA, Tate JE, Golomb E, Keiser HR. Role of neutral endopeptidase in the metabolism of endothelin. Hypertension 20: 89–95, 1992.
 3. Ackermann M, Ritthaler T, Riegger G, Kurtz A, Kramer BK. Endothelin inhibits cAMP‐induced renal release from isolated renal juxtaglomerular cells. J Cardiovasc Pharmacol 26: S135–S137, 1995.
 4. Ahn D, Ge Y, Stricklett PK, Gill P, Taylor D, Hughes AK, Yanagisawa M, Miller L, Nelson RD, Kohan DE. Collecting duct‐specific knockout of endothelin‐1 causes hypertension and sodium retention. J Clin Invest 114: 504–511, 2004.
 5. Akabane S, Yoshimi H, Yoshida K, Kawano Y, Ashida T, Kinoshita O, Matsushima Y, Kawamura M, Imanishi M, Kuramochi M, Omae T. Differential effects of endothelin‐1 and big endothelin on canine kidneys. J Cardiovasc Pharmacol 17(Suppl. 7): S302–S304, 1991.
 6. Albrightson CR, Pullen M, Wu H‐L, Dytko G, Hersh LB, Nambi P. Thrombin‐mediated down‐regulation of endothelin receptors in mesangial cells coincides with the down‐regulation of neutral endopeptidase activity. Mol Pharmacol 47: 1156–1163, 1995.
 7. Allen SW, Chatfield BA, Koppenhafer SA, Schaffer MS, Wolfe RR, Abman SH. Circulating immunoreactive endothelin‐1 in children with pulmonary hypertension. with acute hypoxic pulmonary vasoreactivity Association. Am Rev Respir Dis 148: 519–522, 1993.
 8. Amano M, Ito M, Kimura K, Fukata Y, Chihara K, Nakano T, Matsuura Y, Kaibuchi K. Phosphorylation and activation of myosin by Rho‐associated kinase (Rho‐kinase). J Biol Chem 271: 20246–20249, 1996.
 9. Ambuhl PM, Yang X, Peng Y, Preisig PA, Moe OW, Alpern RJ. Glucocorticoids enhance acid activation of the Na+/H+ exchanger 3 (NHE3). J Clin Invest 103: 429–435, 1999.
 10. Amemiya M, Mori H, Imamura S, Toyoda A, Funayama I, Asano Y, Kusano E, Tabei K. Stimulation of NHE3 in OKP cells by an autocrine mechanism. Nephron Exp Nephrol 96: e23–e30, 2004.
 11. Amiri F, Ko EA, Javeshghani D, Reudelhuber TL, Schiffrin EL. Deleterious combined effects of salt‐loading and endothelial cell restricted endothelin‐1 overexpression on blood pressure and vascular function in mice. J Hypertens 28: 1243–1251.
 12. Amiri F, Virdis A, Neves MF, Iglarz M, Seidah NG, Touyz RM, Reudelhuber TL, Schiffrin EL. Endothelium‐restricted overexpression of human endothelin‐1 causes vascular remodeling and endothelial dysfunction. Circulation 110: 2233–2240, 2004.
 13. Andersen LJ, Norsk P, Johansen LB, Christensen P, Engstrom T, Bie P. Osmoregulatory control of renal sodium excretion after sodium loading in humans. Am J Physiol 275: R1833–R1842, 1998.
 14. Andreis PG, Tortorella C, Malendowicz LK, Nussdorfer GG. Endothelins stimulate aldosterone secretion from dispersed rat adrenal zona glomerulosa cells, acting through ETB receptors coupled with the phospholipase C‐dependent signaling pathway. Peptides 22: 117–122, 2001.
 15. 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.
 16. Arendshorst WJ, Thai TL. Regulation of the renal microcirculation by ryanodine receptors and calcium‐induced calcium release. Curr Opin Nephrol Hypertens 18: 40–49, 2009.
 17. Arinami T, Ishikawa M, Inoue A, Yanagisawa M, Masaki T, Yoshida MC, Hamaguchi H. Chromosomal assignments of the human endothelin family genes: The endothelin‐1 gene(EDN1) to 6p23‐p24, the endothelin‐2 gene(EDN2) to Ip34, and the endothelin‐3 gene(EDN3) to 20q13.2‐q13.3. Am J Hum Genet 48: 990–996, 1991.
 18. Atkins JL, Burg MB. Bicarbonate transport by isolated perfused rat collecting ducts. Am J Physiol 249: F485–F489, 1985.
 19. Backer A, Bokemeyer D, Kramer HJ. Endothelin synthesis and receptors in porcine kidney. Acta Physiol Scand 171: 105–112, 2001.
 20. Badr KF, Murray JJ, Breyer MD, Takahashi K, Inagami T, Harris RC. Mesangial cell, glomerular and renal vascular responses to endothelin in the rat kidney. Elucidation of signal transduction pathways. J Clin Invest 83: 336–342, 1989.
 21. Bailey M, Haton C, Orea V, Sassard J, Bailly C, Unwin R, Imbert‐Teboul M. ETA receptor‐mediated Ca2+ signaling in thin descending limbs of Henle's loop: Impariment in genetic hypertension. Kidney Int 63: 1276–1284, 2003.
 22. Balakrishnan SM, Wang HD, Gopalakrishnan V, Wilson TW, McNeill JR. Effect of an endothelin antagonist on hemodynamic responses to angiotensin II. Hypertension 28: 806–809, 1996.
 23. Baldi E, Dunn MJ. Endothelin binding and receptor down regulation in rat glomerular mesangial cells. J Pharmacol Exp Ther 256: 581–586, 1991.
 24. Ballew JR, Fink GD. Role of endothelin ETB receptor activation in angiotensin II‐induced hypertension: Effects of salt intake. Am J Physiol Heart Circ Physiol 281: H2218–2225, 2001.
 25. Barton M. Reversal of proteinuric renal disease and the emerging role of endothelin. Nat Clin Pract Nephrol 4: 490–501, 2008.
 26. Baum M, Moe OW, Gentry DL, Alpern RJ. Effect of glucocorticoids on renal cortical NHE‐3 and NHE‐1 mRNA. Am J Physiol 267: F437–F442, 1994.
 27. Beck K‐F, Mohaupt MG, Sterzel RB. Endothelin‐1 inhibits cytokine‐stimulated transcription of inducible nitric oxide synthase in glomerular mesangial cells. Kidney Int 48: 1893–1899, 1995.
 28. Benigni A, Perico N, Gaspari F, Zoja C, Bellizzi I, Gabanelli M, Remuzzi G. Increased renal endothelin production in rats with reduced renal mass. Am J Physiol 260: F331–F339, 1991.
 29. Bloom ITM, Bentley FR, Wilson MA, Garrison RN. In vivo effects of endothelin on the renal microcirculation. J Surg Res 54: 274–280, 1993.
 30. Boesen EI. Endothelin ETB receptor heterodimerization: Beyond the ETA receptor. Kidney Int 74: 693–694, 2008.
 31. Boesen EI, Pollock DM. Acute increases of renal medullary osmolality stimulate endothelin release from the kidney. Am J Physiol Renal Physiol 292: F185–F191, 2007.
 32. Booth RE, Tong Q, Medina J, Snyder PM, Patel P, Stockand JD. A region directly following the second transmembrane domain in gamma ENaC is required for normal channel gating. J Biol Chem 278: 41367–41379, 2003.
 33. Bousso‐Mittler D, Galron R, Sokolovsky M. Endothelin/sarafotoxin receptor heterogeneity: Evidence for different glycosylation in receptors from different tissues. Biochem Biophys Res Commun 178: 921–926, 1991.
 34. Bragulat E, de la Sierra A, Antonio MT, Jimenez W, Urbano‐Marquez A, Coca A. Effect of salt intake on endothelium‐derived factors in a group of patients with essential hypertension. Clin Sci (Lond) 101: 73–78, 2001.
 35. Brodsky S, Abassi Z, Wessale J, Ramadan R, Winaver J, Hoffman A. Effects of A‐192621.1, a specific endothelin‐B antagonist, on intrarenal hemodynamic responses to endothelin‐1. J Cardiovasc Pharmacol 36(Suppl 1): S311–S313, 2000.
 36. Brooks DP, DePalma PD, Pullen M, Nambi P. Characterization of canine renal endothelin receptor subtypes and their function. J Pharmacol Exp Ther 268: 1091–1097, 1994.
 37. Brunner F, Bras‐Silva C, Cerdeira AS, Leite‐Moreira AF. Cardiovascular endothelins: Essential regulators of cardiovascular homeostasis. Pharmacol Ther 111: 508–531, 2006.
 38. Bruzzi I, Corna D, Zoja C, Orisio S, Schiffrin EL, Cavallotti D, Remuzzi G, Benigni A. Time course and localization of endothelin‐1 gene expression in a model of renal disease progression. Am J Pathol 151: 1241–1247, 1997.
 39. Buerkert J, Martin D, Trigg D. Segmental analysis of the renal tubule in buffer production and net acid formation. Am J Physiol 244: F442–F454, 1983.
 40. Bugaj V, Pochynyuk O, Mironova E, Vandewalle A, Medina JL, Stockand JD. Regulation of the epithelial Na+ channel by endothelin‐1 in rat collecting duct. Am J Physiol Renal Physiol 295: F1063–F1070, 2008.
 41. Cairns HS, Rogerson ME, Fairbanks LD, Neild GH, Westwick J. Endothelin induces an increase in renal vascular resistance and a fall in glomerular filtration rate in the rabbit isolated perfused kidney. Br J Pharmacol 98: 155–160, 1989.
 42. Capasso G, Unwin R, Rizzo M, Pica A, Giebisch G. Bicarbonate transport along the loop of Henle: Molecular mechanisms and regulation. J Nephrol 15(Suppl 5): S88–S96, 2002.
 43. Carmines PK, Mitchell KD, Navar LG. Effects of calcium antagonists on renal hemodynamics and glomerular function. Kidney Int Suppl 36: S43–S48, 1992.
 44. Carmines PK, Navar LG. Disparate effects of Ca channel blockade on afferent and efferent arteriolar responses to ANG II. Am J Physiol 256: F1015–F1020, 1989.
 45. Casellas D, Carmines PK, Navar LG. Microvascular reactivity of in vitro blood perfused juxtamedullary nephrons from rats. Kidney Int 28: 752–759, 1985.
 46. Casellas D, Navar LG. In vitro perfusion of juxtamedullary nephrons in rats. Am J Physiol 246: F349–F358, 1984.
 47. Cavarape A, Bartoli E. Effects of BQ‐123 on systemic and renal hemodynamic responses to endothelin‐1 in the rat split hydronephrotic kidney. J Hypertens 16: 1449–1458, 1998.
 48. Cavarape A, Endlich N, Assaloni R, Bartoli E, Steinhausen M, Parekh N, Endlich K. Rho‐kinase inhibition blunts renal vasoconstriction induced by distinct signaling pathways in vivo. J Am Soc Nephrol 14: 37–45, 2003.
 49. Cazaubon S, Chaverot N, Romero I, Girault J, Adamson P, Strosberg A, Couraud P. Growth factor activity of endothelin‐1 in primary astrocytes mediated by adhesion‐dependent and ‐independent pathways. J Neurosci 17: 6203–6212, 1997.
 50. Cernacek P, Legault L, Stewart DJ, Levy M. Specific endothelin binding sites in renal medullary collecting duct cells: Lack of interaction with ANP binding and cGMP signalling. Can J Physiol Pharmacol 70: 1167–1174, 1992.
 51. Chahdi A, Sorokin A. Endothelin‐1 induces p66Shc activation through EGF receptor transactivation: Role of beta(1)Pix/Galpha(i3) interaction. Cell Signal 22: 325–329, 2010.
 52. Chambrey R, Paillard M, Podevin RA. Enzymatic and functional evidence for adaptation of the vacuolar H(+)‐ATPase in proximal tubule apical membranes from rats with chronic metabolic acidosis. J Biol Chem 269: 3243–3250, 1994.
 53. Chen L, McNeill JR, Wilson TW, Gopalakrishnan V. Heterogeneity in vascular smooth muscle responsiveness to angiotensin II. Role of endothelin. Hypertension 26: 83–88, 1995.
 54. Chen M, Todd‐Turla K, Wang W‐H, Cao X, Smart A, Brosius FC, Killen PD, Keiser JA, Briggs JP, Schnermann J. Endothlein‐1 mRNa in glomerular and epithelial cells of kidney. Am J Physiol 265: F542–F550, 1993.
 55. Chen X, Berrou J, Nguyen G, Sraer J‐D, Rondeau E. Endothelin‐1 induces rapid and long lasting internalization of the thrombin receptor in human glomerular epithelial cells. Biochem Biophys Res Com 217: 445–451, 1995.
 56. Chigaev A, Lu G, Shi H, Asher C, Xu R, Latter H, Seger R, Garty H, Reuveny E. In vitro phosphorylation of COOH termini of the epithelial Na(+) channel and its effects on channel activity in Xenopus oocytes. Am J Physiol Renal Physiol 280: F1030–F1036, 2001.
 57. Chou SY, Porush JG. Renal actions of endothelin‐1 and endothelin‐3: Interactions with the prostaglandin system and nitric oxide. Am J Kidney Dis 26: 116–123, 1995.
 58. Chow LH, Subramanian S, Nuovo GJ, Miller F, Nord EP. Endothelin receptor mRNA expression in renal medulla identified by in situ PT‐PCR. Am J Physiol 269: F449–F457, 1995.
 59. Chu TS, Cano A, Yanagisawa M, Allpern RJ. Endothelin activates the Na/H antiporter in OKP cells stably transfected with the ETB receptor cDNA. J Am Soc Nephrol 4: 250, 1993.
 60. 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.
 61. Chu TS, Tsuganezawa H, Peng Y, Cano A, Yanagisawa M, Alpern RJ. Role of tyrosine kinase pathways in ETB receptor activation of NHE3. Am J Physiol 271: C763–C771, 1996.
 62. Chu TS, Wu MS, Hsiech BS. Urinary endothelin‐1 in patients with renal disease. J Formos Med Assoc 97: 667–672, 1998.
 63. Chun M, Lin HY, Henis YI, Lodish HF. Endothelin‐induced endocytosis of cell surface ETA receptors. J Biol Chem 270: 10855–10860, 1995.
 64. Claria J, Jimenez W, Villa GLA, Asbert M, Castro A, Llibre J, Arroyo V, Rivera F. Effects of endothelin on renal hemodynamics and segemental sodium handling in conscious rats. Acta Physiol Scand 141: 305–308, 1991.
 65. Clavell AL, Stingo AJ, Margulies KB, Brandt RR, Burnett JC Jr. Role of endothelin receptor subtypes in the in vivo regulation of renal function. Am J Physiol 268: F455–F460, 1995.
 66. Clozel M, Löffler B‐M, Breu V, Hilfiger L, Maire J‐P, Butscha B. Downregulation of endothelin receptors by autocrine production of endothelin‐1. Am J Physiol 265: C188–C192, 1993.
 67. Collino F, Bussolati B, Gerbaudo E, Marozio L, Pelissetto S, Benedetto C, Camussi G. Preeclamptic sera induce nephrin shedding from podocytes through endothelin‐1 release by endothelial glomerular cells. Am J Physiol Renal Physiol 294: F1185–F1194, 2008.
 68. Coroneos EJ, Kester M, Maclouf J, Thomas P, Dunn MJ. Calcium‐regulated protein tyrosine phosphorylation is required for endothelin‐1 to induce prostaglandin endoperoxide synthase‐2 mRNA expression and protein synthesis in mesangial cells. J Am Soc Nephrol 8: 1080–1090, 1997.
 69. Cuzzola F, Mallamaci F, Tripepi G, Parlongo S, Cutrupi S, Cataliotti A, Stancanelli B, Malatino LS, Bellanuova I, Ferri C, Galletti F, Filigheddu F, Glorioso N, Strazzullo P, Zoccali C. Urinary adrenomedullin is related to ET‐1 and salt intake in patients with mild essential hypertension. Am J Hypertens 14: 224–230, 2001.
 70. Cybulsky AV, Stewart DJ, Cybulsky MI. Glomerular epithelial cells produce endothelin‐1. J Am Soc Nephrol 3: 1398–1404, 1993.
 71. Dancu MB, Berardi DE, Vanden Heuvel JP, Tarbell JM. Asynchronous shear stress and circumferential strain reduces endothelial NO synthase and cyclooxygenase‐2 but induces endothelin‐1 gene expression in endothelial cells. Arterioscler Thromb Vasc Biol 24: 2088–2094, 2004.
 72. da Silva RF, Chambaz C, Stergiopulos N, Hayoz D, Silacci P. Transcriptional and post‐transcriptional regulation of preproendothelin‐1 by plaque‐prone hemodynamics. Atherosclerosis 194: 383–390, 2007.
 73. Davenport AP, Kuc RE, Hoskins SL, Karet FE, Fitzgerald F. [125I]‐PD151242: A selective ligand for endothelin ETA receptors in human kidney which localizes to renal vasculature. Br J Pharmacol 113: 1303–1310, 1994.
 74. Dean R, Zhuo J, Alcorn D, Casley D, Mendelsohn FAO. Cellular distribution of 125I‐endothelin‐1 binding in rat kidney following in vivo labeling. Am J Physiol 267: F845–F852, 1994.
 75. de Jesus Ferreira M, Bailly C. Luminal and basolateral endothelin inhibit chloride reabsorption in the mouse thick ascending limb via a Ca(2+)‐independent pathway. J Physiol 505: 749–758, 1997.
 76. Denton K, Shweta A, Finkelstein L, Flower R, Evans R. Effect of endothelin‐1 on regional kidney blood flow and renal arteriole calibre in rabbits. Clin Exp Pharmacol Physiol 31: 494–501, 2004.
 77. Denton KM, Anderson WP. Vascular actions of endothelin in the rabbit kidney. Clin Exp Pharmacol Physiol 17: 861–872, 1990.
 78. De Nucci G, Thomas R, D'Orleans‐Juste P, Antunes E, Walder C, Warner TD, Vane JR. Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and endothelium‐derived relaxing factor. Proc Natl Acad Sci 85: 9797–9800, 1988.
 79. Delarue C, Conlon JM, Remy‐Jouet I, Fournier A, Vaudry H. Endothelins as local activators of adrenocortical cells. J Mol Endocrinol 32: 1–7, 2004.
 80. Dhaun N, Goddard J, Kohan DE, Pollock DM, Schiffrin EL, Webb DJ. Role of endothelin‐1 in clinical hypertension: 20 years on. Hypertension 52: 452–459, 2008.
 81. Dhaun N, Lilitkarntakul P, Macintyre IM, Muilwijk E, Johnston NR, Kluth DC, Webb DJ, Goddard J. Urinary endothelin‐1 in chronic kidney disease and as a marker of disease activity in lupus nephritis. Am J Physiol Renal Physiol 296: F1477–F1483, 2009.
 82. Disashi T, Nonoguchi H, Iwaoka T, Naomi S, Nakayama Y, Shimada K, Tanzawa K, Tomita K. Endothelin converting enzyme‐1 gene expression in the kidney of spontaneously hypertensive rats. Hypertension 30: 1591–1597, 1997.
 83. Dorado F, Velasco S, Esparis‐Ogando A, Pericacho M, Pandiella A, Silva J, Lopez‐Novoa JM, Rodriguez‐Barbero A. The mitogen‐activated protein kinase Erk5 mediates human mesangial cell activation. Nephrol Dial Transplant 23: 3403–3411, 2008.
 84. D'Orleans‐Juste P, Plante M, Honore JC, Carrier E, Labonte J. Synthesis and degradation of endothelin‐1. Can J Physiol Pharmacol 81: 503–510, 2003.
 85. Douglas SA, Ohlstein EH. Signal transduction mechanisms mediating the vascular actions of endothelin. J Vasc Res 34: 152–164, 1997.
 86. Douthwaite JA, Lees DM, Corder R. A role for increased mRNA stability in the induction of endothelin‐1 synthesis by lipopolysaccharide. Biochem Pharmacol 66: 589–594, 2003.
 87. Dulin N, Sorokin A, Reed E, Elliott S, Kehrl J, Dunn M. RGS3 inhibits G protein‐mediated signaling via translocation to the membrane and binding to Galpha. Mol Cell Biol 19: 714–723, 1999.
 88. d'Uscio LV, Moreau P, Shaw S, Takase H, Barton M, Luscher TF. Effects of chronic ETA‐receptor blockade in angiotensin II‐induced hypertension. Hypertension 29: 435–441, 1997.
 89. Edwards RM, Pullen M, Nambi P. Activation of endothelin ETB receptors increases glomerular cGMP via an L‐arginine‐dependent pathway. Am J Physiol 263: F1020–1025, 1992.
 90. Edwards RM, Stack EJ, Pullen M, Nambi P. Endothelin inhibits vasopressin action in rat inner medullary collecting duct via the ETB receptor. J Pharmacol Exp Ther 267: 1028–1033, 1993.
 91. Edwards RM, Trizna W. Characterization of 125I‐endothelin‐1 binding to rat and rabbit renal microvasculature. J Pharmacol Exp Ther 274: 1064–1089, 1995.
 92. Edwards RM, Trizna W, Ohlstein EH. Renal microvascular effects of endothelin. Am J Physiol 259: F217–F221, 1990.
 93. 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.
 94. Eiam‐Ong S, Kurtzman NA, Sabatini S. Regulation of collecting tubule adenosine triphosphatases by aldosterone and potassium. J Clin Invest 91: 2385–2392, 1993.
 95. Elmarakby AA, Dabbs Loomis E, Pollock JS, Pollock DM. ETA receptor blockade attenuates hypertension and decreases reactive oxygen species in ETB receptor‐deficient rats. J Cardiovasc Pharmacol 44(Suppl 1): S7–S10, 2004.
 96. Elmarakby AA, Quigley JE, Imig JD, Pollock JS, Pollock DM. TNF‐alpha inhibition reduces renal injury in DOCA‐salt hypertensive rats. Am J Physiol Regul Integr Comp Physiol 294: R76–R83, 2008.
 97. Emori T, Hirata Y, Ohta K, Kanno K, Eguchi S, Imai T, Shichiri M, Marumo F. Cellular mechanism of endothelin‐1 release by angiotensin and vasopressin. Hypertension 18: 165–170, 1991.
 98. Emori T, Hirata Y, Ohta K, Shichiri M, Marumo F. Secretory mechanism of immunoreactive endothelin in cultured bovine endothelial cells. Biochem Biophys Res Commun 160: 93–100, 1989.
 99. Emoto N, Yanagisawa M. Endothelin‐converting enzyme‐2 is a membrane‐bound phosphoramidon‐sensitive metalloprotease with acidic pH optimum. J Biol Chem 270: 15262–15268, 1995.
 100. Endemann D, Schweda F, Stubanus M, Ittner KP, Fischereder M, Kammerl MC, Kramer BK. Naftidrofuryl exerts antiserotonergic but no endothelin‐receptor blocking effects in AS4.1 cells, juxtaglomerular cells and isolated perfused rat kidneys. J Cardiovasc Pharmacol 39: 1–8, 2002.
 101. Endlich K, Hoffend J, Steinhausen M. Localization of endothelin ETA and ETB receptor‐mediated constriction in the renal microcirculation of rats. J Physiol 497(Pt 1): 211–218, 1996.
 102. Ergul S, Parish DC, Puett D, Ergul A. Racial differences in plasma endothelin‐1 concentrations in individuals with essential hypertension. Hypertension 28: 652–655, 1996.
 103. Escalante B, McGiff J, Oyekan A. Role of cytochrome P‐450 arachidonate metabolites in endothelin signaling in rat proximal tubule. Am J Physiol 282: F144–F150, 2002.
 104. Evangelista S, Maggi CA, Castellucci A. Effect of endothelin (ET)‐1, ET‐3, and ET‐(16‐21) on the isolated and perfused rat kidney from normotensive and spontaneously hypertensive rats. Jpn J Pharmacol 59: 239–241, 1992.
 105. Evans NJ, Walker JW. Sustained Ca2+ signaling and delayed internalization associated with endothelin receptor heterodimers linked through a PDZ finger. Can J Physiol Pharmacol 86: 526–535, 2008.
 106. Evans R, Madden A, Oliver J, Lewis T. Effects of ETA‐ and ETB‐ receptor antagonists on regional kidney blood flow, and response to intravenous endothelin‐1, in anaesthetized rabbits. J Hypertens 19: 1789–1799, 2001.
 107. Evans RG, Eppel GA, Anderson WP, Denton KM. Mechanisms underlying the differential control of blood flow in the renal medulla and cortex. J Hypertens 22: 1439–1451, 2004.
 108. Evans RR, Phillips BG, Singh G, Bauman JL, Gulati A. Racial and gender differences in endothelin‐1. Am J Cardiol 78: 486–488, 1996.
 109. Falin RA, Cotton CU. Acute downregulation of ENaC by EGF involves the PY motif and putative ERK phosphorylation site. J Gen Physiol 130: 313–328, 2007.
 110. Fattal I, Abassi Z, Ovcharenko E, Shimada K, Takahashi M, Hoffman A, Winaver J. Effect of dietary sodium intake on the expression of endothelin‐converting enzyme in the renal medulla. Nephron Physiol 98: 89–96, 2004.
 111. Fellner SK, Arendshorst W. Endothelin‐A and ‐B receptors, superoxide, and Ca2+ signaling in afferent arterioles. Am J Physiol Renal Physiol 292: F175–F184, 2007.
 112. Fellner SK, Arendshorst WJ. Endothelin A and B receptors of preglomerular vascular smooth muscle cells. Kidney Int 65: 1810–1817, 2004.
 113. Fernandez R, Lopes MJ, de Lira RF, Dantas WF, Cragoe Junior EJ, Malnic G. Mechanism of acidification along cortical distal tubule of the rat. Am J Physiol 266: F218–F226, 1994.
 114. Ferri C, Bellini C, Desideri G, Mazzocchi C, De Siati L, Santucci A. Elevated plasma and urinary endothelin‐I levels in human salt‐sensitive hypertension. Clin Sci 93: 35–41, 1997.
 115. Foschi M, Sorokin A, Pratt P, McGinty A, La Villa G, Franchi F, Dunn M. PreproEndothelin‐1 expression in human mesangial cells: Evidence for a p38 mitogen‐activated protein kinase/protein kinases‐C‐dependent mechanism. J Am Soc Nephrol 12: 1137–1150, 2001.
 116. Francis B, Abassi Z, Heyman S, Winaver J, Hoffman A. Differential regulation of ETA and ETB in the renal tissue of rats with compensated and decompensated heart failure. J Cardiovasc Pharmacol 44: S362–S365, 2004.
 117. Frank K, Zeier M, Gross ML, Waldherr R, Ritz E, Amann K. Comprehensive immunohistological analysis of the endothelin system in human kidney grafts. Nephrol Dial Transplant 21: 1365–1372, 2006.
 118. Freed MI, Thompson KA, Wilson DE, Etheredge R, Jorkasky DK. Endothelin receptor antagonism does not alter renal hemodynamic responses or urinary sodium excretion in healthy humans. J Am Soc Nephrol 7: 1580, 1996.
 119. Fretschner M, Endlich K, Gulbins E, Lang RE, Schlottmann K, Steinhausen M. Effects of endothelin on the renal microcirculation of the split hydronephrotic rat kidney. Renal Physiol Biochem 14: 112–127, 1991.
 120. Fukunaga M, Fujiwara Y, Ochi S, Yokoyama K, Shoji T, Fukuhara Y, Orita Y, Kamada T, Badr KF, Ueda N. Mechanism of induction of prostaglandin E2 production by endothelin 1 in cultured rat mesangial cells. Exp Nephrol 4: 340–349, 1996.
 121. Furuya S, Naruse S, Nakayama T, Nokihara K. Effect and distribution of intravenously injected 125I‐endothelin‐1 in rat kidney and lung examined by electron microscopic radioautography. Anat Embryol (Berl) 185: 87–96, 1992.
 122. Gallego MS, Ling BN. Regulation of amiloride‐sensitive sodium channels by endothelin‐1 in distal nephron cells. Am J Physiol 271: F451–F460, 1996.
 123. Garcia NH, Garvin JL. Endothelin's biphasic effect on fluid absorption in the proximal straight tubule. J Clin Invest 93: 2572–2577, 1994.
 124. Gardner JP, Maher E, Aviv A. Calcium mobilization and Na+/H+ antiport activation by endothelin in human skin fibroblasts. FEBS Lett 256: 38–42, 1989.
 125. Gariepy C, Wang Y, Nguyen N, Li S, Yanagisawa M. Salt‐sensitive hypertension in ETB‐deficient rats is not due to mechanisms intrinsic to the kidney. Seventh International Conference on Endothelin, Edinburgh, Scotland, 2001, p. O46.
 126. Gariepy CE, Ohuchi T, Williams SC, Richardson JA, Yanagisawa M. Salt‐sensitive hypertension in endothelin‐B receptor‐deficient rats. J Clin Invest 105: 925–933, 2000.
 127. 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.
 128. Ge Y, Ahn D, Stricklett PK, Hughes AK, Yanagisawa M, Verbalis JG, Kohan DE. Collecting duct‐specific knockout of endothelin‐1 alters vasopressin regulation of urine osmolality. Am J Physiol Renal Physiol 288: F912–F920, 2005.
 129. Ge Y, Bagnall A, Stricklett PK, Strait K, Webb DJ, Kotelevtsev Y, Kohan DE. Collecting duct‐specific knockout of the endothelin B receptor causes hypertension and sodium retention. Am J Physiol Renal Physiol 291: F1274–F1280, 2006.
 130. Ge Y, Huang Y, Kohan DE. Role of the renin‐angiotensin‐aldosterone system in collecting duct‐derived endothelin‐1 regulation of blood pressure. Can J Physiol Pharmacol 86: 329–336, 2008.
 131. Ge Y, Strait KA, Stricklett PK, Yang T, Kohan DE. Role of prostaglandins in collecting duct‐derived endothelin‐1 regulation of blood pressure and water excretion. Am J Physiol Renal Physiol 293: F1805–F1810, 2007.
 132. Ge Y, Stricklett PK, Hughes AK, Yanagisawa M, Kohan DE. Collecting duct‐specific knockout of the endothelin A receptor alters renal vasopressin responsiveness, but not sodium excretion or blood pressure. Am J Physiol Renal Physiol 289: F692–F698, 2005.
 133. 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.
 134. Gellai M, DeWolf R, Pullen M, Nambi P. Distribution and functional role of renal ET receptor subtypes in normotensive and hypertensive rats. Kidney Int 46: 1287–1294, 1994.
 135. Gilmore ES, Stutts MJ, Milgram SL. SRC family kinases mediate epithelial Na+ channel inhibition by endothelin. J Biol Chem 276: 42610–42617, 2001.
 136. Girchev R, Backer A, Markova P, Kramer H. Impaired response of the denervated kidney to endothelin receptor blockade in normotensive and spontaneously hypertensive rats. Kidney Int 65: 982–989, 2004.
 137. Goetz K, Wang BC, Leadley RJ, Zhu JL, Madwed J, Bie P. Endothelin and sarafotoxin produce dissimilar effects on renal blood flow, but both block the antidiuretic effects of vasopressin. Proc Soc Exp Biol Med 191: 425–427, 1989.
 138. Goruppi S, Bonventre J, Kyriakis J. Signaling pathways and late‐onset gene induction associated with renal mesangial cell hypertrophy. EMBO J 216: 5427–5436, 2002.
 139. Gregan B, Jurgensen J, Papsdorf G, Furkert J, Schaefer M, Beyermann M, Rosenthal W, Oksche A. Ligand‐dependent differences in the internalization of endothelin A and endothelin B receptor heterodimers. J Biol Chem 279: 27679–27687, 2004.
 140. Gregan B, Schaefer M, Rosenthal W, Oksche A. Fluorescence resonance energy transfer analysis reveals the existence of endothelin‐A and endothelin‐B receptor homodimers. J Cardiovasc Pharmacol 44(Suppl 1): S30–S33, 2004.
 141. Grond J, Beukers JY, Schilthuis MS, Weening JJ, Elema JD. Analysis of renal structural and functional features in two rat strains with a different susceptibility to glomerular sclerosis. Lab Invest 54: 77–83, 1986.
 142. Gulbins E, Hoffend J, Zou AP, Dietrich MS, Schlottmann K, Cavarape A, Steinhausen M. Endothelin and endothelium‐derived relaxing factor control of basal renovascular tone in hydronephrotic rat kidneys. J Physiol 469: 571–582, 1993.
 143. Gumz ML, Popp MP, Wingo CS, Cain BD. Early transcriptional effects of aldosterone in a mouse inner medullary collecting duct cell line. Am J Physiol Renal Physiol 285: F664–F673, 2003.
 144. Guntupalli J, DuBose TDJ. Effects of endothelin on rat renal proximal tubule Na+‐Pi contransport and Na+/H+ exchange. Am J Physiol 266: F658–F666, 1994.
 145. Guo X, Yang T. Endothelin B receptor antagonism in the rat renal medulla reduces urine flow rate and sodium excretion. Exp Biol Med (Maywood) 231: 1001–1005, 2006.
 146. Harrington JT, Lemann J, Jr. The metabolic production and disposal of acid and alkali. Med Clin North Am 54: 1543–1554, 1970.
 147. Harris PJ, Zhuo J, Mendelsohn FAO, Skinner SL. Haemodynamic and renal tubular effects of low doses of endothelin in anesthetized rats. J Physiol 433: 25–39, 1991.
 148. Harrison VJ, Barnes K, turner AJ, Wood E, Corder R, Vane JR. Identification of endothelin 1 and big endothelin 1 in secretory vesicles isolated from bovine aortic endothelial cells. Proc Natl Acad Sci U S A 92: 6344–6348, 1995.
 149. Harshfield GA, Alpert BS, Pulliam DA, Willey ES, Somes GW, Stapelton FB. Sodium excretion and racial differences in ambulatory blood pressure patterns. Hypertension 18: 813–818, 1991.
 150. Hatae N, Aksentijevich N, Zemkova HW, Kretschmannova K, Tomic M, Stojilkovic SS. Cloning and functional identification of novel endothelin receptor type A isoforms in pituitary. Mol Endocrinol 21: 1192–1204, 2007.
 151. Haug C, Linder TM, Schmid‐Kotsas A, Hetzel S, Ernst F, Gruenert A, Jehle PM. Inhibitory effect of epidermal growth factor and hepatocyte growth factor on endothelin‐1 release by rabbit proximal tubule cells. J Cardiovasc Pharmacol 36: S248–S251, 2000.
 152. Hayashi K, Loutzenhiser R, Epstein M. Direct evidence that thromboxane mimetic U44069 preferentially constricts the afferent arteriole. J Am Soc Nephrol 8: 25–31, 1997.
 153. Heller J, Kramer HJ, Horacek V. Action of endothelin‐1 on glomerular haemodynamics in the dog: Lack of direct effects on glomerular ultrafiltration coefficient. Clin Sci (Lond) 90: 385–391, 1996.
 154. Helms MN, Yu L, Malik B, Kleinhenz DJ, Hart CM, Eaton DC. Role of SGK1 in nitric oxide inhibition of ENaC in Na+‐transporting epithelia. Am J Physiol Cell Physiol 289: C717–C726, 2005.
 155. Hercule H, Oyekan A. Role of NO and cytochrome P‐450‐derived eicosanoids in ET‐1‐induced changes in intrarenal hemodynamics in rats. Am J Physiol 279: R2132–R2141, 2000.
 156. Hercule H, Oyekan A. Renal cytochrome p450 oxygenases and preglomerular vascular response to arachidonic acid and endothelin‐1 following ischemia/reperfusion. J Pharmacol Exp Ther 302: 717–724, 2002.
 157. Herizi A, Jover B, Bouriquet N, Mimran A. Prevention of the cardiovascular and renal effects of angiotensin II by endothelin blockade. Hypertension 31: 10–14, 1998.
 158. Herman WH, Emancipator SN, Rhoten RL, Simonson MS. Vascular and glomerular expression of endothelin‐1 in normal human kidney. Am J Physiol 275: F8–F17, 1998.
 159. Herrera M, Garvin J. Endothelin stimulates endothelial nitric oxide synthase expression in the thick ascending limb. Am J Physiol 287: F231–F235, 2004.
 160. Herrera M, Garvin J. A high‐salt diet stimulates thick ascending limb eNOS expression by raising medullary osmolality and increasing release of endothelin‐1. Am J Physiol 288: F58–F64, 2005.
 161. Herrera M, Hong NJ, Ortiz PA, Garvin JL. Endothelin‐1 inhibits thick ascending limb transport via Akt‐stimulated nitric oxide production. J Biol Chem 284: 1454–1460, 2009.
 162. Hirahashi J, Nakaki T, Hishikawa K, Marumo T, Yasumori T, Hayashi M, Suzuki H, Saruta T. Endothelin‐1 inhibits induction of nitric oxide synthase and GTP cyclohydrolase I in rat mesangial cells. Pharmacology 53: 241–249, 1996.
 163. Hoffman A, Abassi ZA, Brodsky S, Ramadan R, Winaver J. Mechanisms of big endothelin‐I‐induced diuresis and natriuresis. Hypertension 35: 732–739, 2000.
 164. Hoffman A, Grossman E, Goldstein DS, Gill JR Jr, Keiser HR. Urinary excretion rate of endothelin‐1 in patients with essential hypertension and salt sensitivity. Kidney Int 45: 556–560, 1993.
 165. Hoffman A, Grossman E, Goldstein DS, Gill JRJ, Keiser HR. Urinary excretion rate of endothelin‐1 in patients with essential hypertension and salt sensitivity. Kidney Int 45: 556–560, 1994.
 166. Honing M, Hijmering M, Ballard D, Yang Y, Padley R, Morrison P, Rabelink T. Selective ETA receptor antagonism with ABT‐627 attenuates all renal effects of endothelin in humans. J Am Soc Nephrol 11: 1498–1504, 2000.
 167. Horie M, Uchida S, Yanagisawa M, Matsushita Y, Kurokawa K, Ogata E. Mechanisms of endothelin‐1 mRNA and peptides induction by TGF‐beta and TPA in MDCK cells. J Cardiovasc Pharmacol 17(Suppl 7): S222–S225, 1991.
 168. Hosoda K, Nakao K, Tamura N, Arai H, Ogawa Y, Suga S, Nakanishi S, Imura H. Organization, structure, chromosomal assignment, and expression of the gene encoding the human endothelin‐A receptor. J Biol Chem 267: 18797–18804, 1992.
 169. Hovater MB, Olteanu D, Hanson EL, Cheng NL, Siroky B, Fintha A, Komlosi P, Liu W, Satlin LM, Bell PD, Yoder BK, Schwiebert EM. Loss of apical monocilia on collecting duct principal cells impairs ATP secretion across the apical cell surface and ATP‐dependent and flow‐induced calcium signals. Purinergic Signal 4: 155–170, 2008.
 170. Hsieh TJ, Lin SR, Lee YJ, Shin SJ, Lai YH, Hsu CH, Tsai JH. Increased renal medullary endothelin‐1 synthesis in prehypertensive DOCA‐ and salt‐treated rats. Am J Physiol Renal Physiol 279: F112–F121, 2000.
 171. Hua H, Munk S, Whiteside CI. Endothelin‐1 activates mesangial cell ERK1/2 via EGF‐receptor transactivation and caveolin‐1 interaction. Am J Physiol Renal Physiol 284: F303–F312, 2003.
 172. Hubel CA, Highsmith RF. Endothelin‐induced changes in intracellular pH and Ca2+ in coronary smooth muscle: Role of Na(+)‐H+ exchange. Biochem J 310(Pt 3): 1013–1020, 1995.
 173. Hughes AK, Cline RC, Kohan DE. Alterations in renal endothelin production in the spontaneously hypertensive rat. Hypertension 20: 666–673, 1992.
 174. Hughes AK, Padilla E, Kutchera WA, Michael JR, Kohan DE. Endothelin‐1 induction of cyclooxygenase‐2 expression in rat mesangial cells. Kidney Int 47: 53–61, 1995.
 175. Hughes AK, Stricklett PK, Kishore BK, Kohan DE. Adenosine triphosphate inhibits endothelin‐1 production by rat inner medullary collecting duct cells. Exp Biol Med (Maywood) 231: 1006–1009, 2006.
 176. Hwang YS, Hsieh TJ, Lee YJ, Tsai JH. Circadian rhythm of urinary endothelin‐1 excretion in mild hypertensive patients. Am J Hypertens 11: 1344–1351, 1998.
 177. Iglarz M, Schiffrin EL. Role of endothelin‐1 in hypertension. Curr Hypertens Rep 5: 144–148, 2003.
 178. Ikeda M, Kohno M, Takeda T. Endothelin production in cultured mesangial cells of spontaneously hypertensive rats. Hypertension 25: 1196–1201, 1995.
 179. Ikeda S, Emoto N, Alimsardjono H, Yokoyama M, Matsuo M. Molecular isolation and characterization of novel four subisoforms of ECE‐2. Biochem Biophys Res Commun 293: 421–426, 2002.
 180. Imai T, Hirata Y, Emori T, Yanagisawa M, Masaki T, Marumo F. Induction of endothelin‐1 gene by angiotensin and vasopressin in endothelial cells. Hypertension 19: 753–757, 1992.
 181. Imamura T, Huang J, Dalle S, Ugi S, Usui I, Luttrell L, Miller W, Lefkowitz R, Olefsky J. beta‐Arrestin‐mediated recruitment of the Src family kinase Yes mediates endothelin‐1‐stimulated glucose transport. J Biol Chem 276: 43663–43667, 2001.
 182. Imig JD. Eicosanoid regulation of the renal vasculature. Am J Physiol Renal Physiol 279: F965–981, 2000.
 183. Imig JD, Pham BT, LeBlanc EA, Reddy KM, Falck JR, Inscho EW. Cytochrome P450 and cyclooxygenase metabolites contribute to the endothelin‐1 afferent arteriolar vasoconstrictor and calcium responses. Hypertension 35: 307–312, 2000.
 184. Inoue A, Yanagisawa M, Takuwa Y, Mitsui Y, Kobayashi M, Masaki T. The human preproendothelin‐1 gene. J Biol Chem 264: 14954–14959, 1989.
 185. Inscho EW, Cook AK, Webb RC, Jin LM. Rho‐kinase inhibition reduces pressure‐mediated autoregulatory adjustments in afferent arteriolar diameter. Am J Physiol Renal Physiol 296: F590–F597, 2009.
 186. Inscho EW, Imig JD, Cook AK, Pollock DM. ETA and ETB receptors differentially modulate afferent and efferent arteriolar responses to endothelin. Br J Pharmacol 146: 1019–1026, 2005.
 187. Ishii K, Warner TD, Sheng H, Murad F. Endothelin increases cyclic GMP levels in LLC‐PK1 porcine kidney epithelial cells via formation of an endothelium‐derived relaxing factor‐like substance. J Pharmacol Exp Ther 259: 1102–1108, 1991.
 188. Ito H, Hirata Y, Adachi S, Tanaka M, Tsujino M, Koike A, Nogami A, Murumo F, Hiroe M. Endothelin‐1 is an autocrine/paracrine factor in the mechanism of angiotensin II‐induced hypertrophy in cultured rat cardiomyocytes. J Clin Invest 92: 398–403, 1993.
 189. Itoh K, Kase R, Shimmoto M, Satake A, Sakuraba H, Suzuki Y. Protective protein as an endogenous endothelin degradation enzyme in human tissues. J Biol Chem 270: 515–518, 1995.
 190. Iwasaki S, Homma T, Matsuda Y, Kon V. Endothelin receptor subtype B mediates autoinduction of endothelin‐1 in rat mesangial cells. J Biol Chem 270: 6997–7003, 1995.
 191. Jackman HL, Morris PW, Deddish PA, Skidgel RA, Erdos EG. Inactivation of endothelin I by deamidase (lysosomal protective protein). J Biol Chem 267: 2872–2875, 1992.
 192. Jackson RW, Treiber FA, Harshfield GA, Waller JL, Pollock JS, Pollock DM. Urinary excretion of vasoactive factors are correlated to sodium excretion. Am J Hypertens 14: 1003–1006, 2001.
 193. Jacques D, Sader S, Perreault C, Abdel‐Samad D, Jules F, Provost C. NPY, ET‐1, and Ang II nuclear receptors in human endocardial endothelial cells. Can J Physiol Pharmacol 84: 299–307, 2006.
 194. Jaffer FE, Knauss TC, Poptic E, Abboud HE. Endothelin stimulates PDGF secretion in cultured human mesangial cells. Kidney Int 38: 1193–1198, 1990.
 195. Januszewicz A, Lapinski M, Symonides B, Dabrowska E, Kuch‐Wocial A, Trzepla E, Ignatowska‐Switalska H, Wocial B, Chodakowska J, Januszewicz W. Elevated endothelin‐1 plasma concentration in patients with essential hypertension. J Cardiovasc Risk 1: 81–85, 1994.
 196. Just A, Whitten CL, Arendshorst WJ. Reactive oxygen species participate in acute renal vasoconstrictor responses induced by ETA and ETB receptors. Am J Physiol Renal Physiol 294: F719–F728, 2008.
 197. Kamphuis C, Yates NA, McDaugall JG. Differential blockade of the renal vasoconstrictor and iduretic responses to endothelin‐1 by endothelin antagonist. Clin Exp Pharmacol Physiol 21: 329–333, 1994.
 198. Karet FE, Davenport AP. Localization of endothelin peptides in human kidney. Kidney Int 49: 382–387, 1996.
 199. Karet FE, Kuc RE, Davenport AP. Novel ligands BQ123 and BQ3020 characterize endothelin receptor subtypes ETA and ETB in human kidney. Kidney Int 44: 36–42, 1993.
 200. Kasinath BS, Fried TA, Davalath S, Marsden PA. Glomerular epithelial cells synthesize endothelin peptides. Am J Pathol 141: 279–283, 1992.
 201. Katoh T, Chang H, Uchida S, Okuda T, Kurokawa K. Direct effects of endothelin in the rat kidney. Am J Physiol 258: F397–F402, 1990.
 202. Kawabata M, Han WH, Ise T, Kobayashi K, Takabatake T. Role of endogenous endothelin and nitric oxide in tubuloglomerular feedback. Kidney Int Suppl 55: S135–S137, 1996.
 203. Khanna A, Simoni J, Hacker C, Duran MJ, Wesson DE. Increased endothelin activity mediates augmented distal nephron acidification induced by dietary protein. J Am Soc Nephrol 15: 2266–2275, 2004.
 204. Khanna A, Simoni J, Wesson DE. Endothelin‐induced increased aldosterone activity mediates augmented distal nephron acidification as a result of dietary protein. J Am Soc Nephrol 16: 1929–1935, 2005.
 205. King AJ, Brenner BM, Anderson S. Endothelin: A potent renal and systemic vasoconstrictor peptide. Am J Physiol 256: F1051–F1058, 1989.
 206. Kirkby NS, Hadoke PW, Bagnall AJ, Webb DJ. The endothelin system as a therapeutic target in cardiovascular disease: Great expectations or bleak house? Br J Pharmacol 153: 1105–1119, 2008.
 207. Kirton CA, Loutzenhiser R. Alterations in basal protein kinase C activity modulate renal afferent arteriolar myogenic reactivity. Am J Physiol 275: H467–H475, 1998.
 208. Kitamura K, Shiraishi N, Singer W, Handlogten M, Tomita K, Miller R. Endothelin‐B receptors activate Galpha13. Am J Physiol 276: C930–C937, 1999.
 209. Kitamura K, Tanaka T, Kato J, Eto T, Tanaka K. Regional distribution of immunoreactive endothelin in porcine tissue: Abundance in inner medulla of kidney. Biochem Biophys Res Commun 161: 348–352, 1989.
 210. Kitamura K, Tanaka T, Kato J, Qgawa Y, Eto T, Tanaka K. Immunoreactive endothelin in rat kidney inner medulla: Marked decrease in spontaneously hypertensive rats. Biochem Biophys Res Commun 162: 38–44, 1989.
 211. Knepper MA, Packer R, Good DW. Ammonium transport in the kidney. Physiol Rev 69: 179–249, 1989.
 212. Kohan D. Endothelins in the normal and diseased kidney. Am J Kid Dis 29: 2–26, 1997.
 213. Kohan DE. Endothelin synthesis by rabbit renal tubule cells. Am J Physiol 261: F221–F226, 1991.
 214. Kohan DE. Production of endothelin‐1 by rat mesangial cells: Regulation by tumor necrosis factor. J Lab Clin Med 119: 477–484, 1992.
 215. Kohan DE. Endothelin production by human inner medullary collecting duct cells. J Am Soc Nephrol 3: 1719–1721, 1993.
 216. Kohan DE, Fiedorek FTJ. Endothelin synthesis by rat inner medullary collecting duct cells. J Am Soc Nephrol 2: 150–155, 1991.
 217. Kohan DE, Hughes AK, Perkins SP. Characterization of endothelin receptors in the inner medullary collecting duct of the rat. J Biol Chem 267: 12336–12340, 1992.
 218. Kohan DE, Padilla E. Endothelin‐1 is an autocrine factor in rat inner medullary collecting ducts. Am J Physiol 263: F607–F612, 1992.
 219. Kohan DE, Padilla E. Osmolar regulation of endothelin‐1 production by rat inner medullary collecting duct. J Clin Invest 91: 1235–1240, 1993.
 220. Kohan DE, Padilla E. Endothelin‐1 production by rat inner medullary collecting ducts: Effect of nitric oxide, cGMP, and immune cytokines. Am J Physiol 266: F291–F297, 1994.
 221. Kohan DE, Padilla E, Hughes AK. Endothelin B receptor mediates ET‐1 effects on cAMP and PGE2 accumulation in rat IMCD. Am J Physiol 265: F670–F676, 1993.
 222. Kohno M, Horio T, Ikeda M, Yokokawa K, Fukui T, Yasunari K, Kurihara N, Takeda T. Angiotensin II stimulates endothelin‐1 secretion in cultured rat mesangial cells. Kidney Int 42: 860–866, 1992.
 223. Kohno M, Ikeda M, Johchi M, Horio T, Yasunari K, Kurihara N, Takeda T. Interaction of PDGF and natriuretic peptides on mesangial cell proliferation and endothelin secretion. Am J Physiol 265: E673–E679, 1993.
 224. Kohno M, Murakawa K, Yasunari K, Yokokawa K, Horio T, Kurihara N, Takeda T. Prolonged blood pressure elevation after endothelin administration in bilaterally nephrectomized rats. Metabolism 38: 712–713, 1989.
 225. Kohno M, Yokokawa K, Mandal AK, Horio T, Yasunari K, Takeda T. Cardiac natriuretic peptides inhibit cyclosporine‐induced production of endothelin in cultured rat mesangial cells. Metabolism 44: 404–409, 1995.
 226. 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.
 227. Kon V, Badr KF. Biological actions and pathophysiologic significance of endothelin in the kidney. Kidney Int 40: 1–12, 1991.
 228. Kon V, Yoshioka T, Fogo A, Ichikawa I. Glomerular actions of endothelin in vivo. J Clin Invest 83: 1762–1767, 1989.
 229. Kopp UC, Cicha MZ, Smith LA. Activation of endothelin‐a receptors contributes to angiotensin‐induced suppression of renal sensory nerve activation. Hypertension 49: 141–147, 2007.
 230. Kopp UC, Cicha MZ, Smith LA. Angiotensin blocks substance P release from renal sensory nerves by inhibiting PGE2‐mediated activation of cAMP. Am J Physiol Renal Physiol 285: F472–F483, 2003.
 231. Kopp UC, Cicha MZ, Smith LA. Endogenous angiotensin modulates PGE(2)‐mediated release of substance P from renal mechanosensory nerve fibers. Am J Physiol Regul Integr Comp Physiol 282: R19–R30, 2002.
 232. Kopp UC, Cicha MZ, Smith LA. Differential effects of endothelin on activation of renal mechanosensory nerves: Stimulatory in high‐sodium diet and inhibitory in low‐sodium diet. Am J Physiol Regul Integr Comp Physiol 291: R1545–R1556, 2006.
 233. Kopp UC, Grisk O, Cicha MZ, Smith LA, Steinbach A, Schluter T, Mahler N, Hokfelt T. Dietary sodium modulates the interaction between efferent renal sympathetic nerve activity and afferent renal nerve activity: Role of endothelin. Am J Physiol Regul Integr Comp Physiol 297: R337–R351, 2009.
 234. Kopp UC, Olson LA, DiBona GF. Renorenal reflex responses to mechano‐ and chemoreceptor stimulation in the dog and rat. Am J Physiol 246: F67–F77, 1984.
 235. Korbmacher C, Boulpaep EL, Giebisch G, Geibel J. Endothelin increases [Ca2+]i in M‐1 mouse cortical collecting duct cells by a dual mechanism. Am J Physiol 265: C349–C357, 1993.
 236. Kramer H, Hashemi T, Backer A, Bokemeyer D. Hyperosmolality induced by betaine or urea stimulates endothelin synthesis by differential activation of ERK and p38 MAP kinase in MDCK cells. Kidney Blood Press Res 25: 65–70, 2002.
 237. Kramer RE, Robinson TV, Schneider EG, Smith TG. Direct modulation of basal and angiotensin II‐stimulated aldosterone secretion by hydrogen ions. J Endocrinol 166: 183–194, 2000.
 238. Krum H, Viskoper RJ, Lacourciere Y, Budde M, Charlon V. The effect of an endothelin‐receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. Bosentan Hypertension Investigators. N Engl J Med 338: 784–790, 1998.
 239. Kuc R, Davenport AP. Comparison of endothelin‐A and endothelin‐B receptor distribution visualized by radioligand binding versus immunocytochemical localization using subtype selective antisera. J Cardiovasc Pharmacol 44(Suppl 1): S224–S226, 2004.
 240. Kuc RE, Davenport AP. Endothelin‐A‐receptors in human aorta and pulmonary arteries are downregulated in patients with cardiovascular disease: An adaptive response to increased levels of endothelin‐1? J Cardiovasc Pharmacol 36: S377–S379, 2000.
 241. Kunau RT Jr, Walker KA. Total CO2 absorption in the distal tubule of the rat. Am J Physiol 252: F468–F473, 1987.
 242. Kunau RT Jr, Walker KA. Distal tubular acidification in the remnant kidney. Am J Physiol 258: F69–F74, 1990.
 243. Kurokawa K, Yoshitomi K, Ikeda M, Uchida S, Naruse M, Imai M. Regulation of cortical collecting duct function: Effect of endothelin. Am Heart J 125: 582–588, 1993.
 244. Kurtz A, Kaissling B, Busse R, Baier W. Endothelial cells modulate renin secretion from isolated mouse juxtaglomerular cells. J Clin Invest 88: 1147–1154, 1991.
 245. Kurtz I, Maher T, Hulter HN, Schambelan M, Sebastian A. Effect of diet on plasma acid‐base composition in normal humans. Kidney Int 24: 670–680, 1983.
 246. Laghmani K, Preisig P, Alpern R. 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.
 247. Laghmani K, Preisig P, Moe O, Yangisawa M, Alpern R. Endothelin‐1/endothelin‐B receptor‐mediated increase in NHE3 activity in chronic metabolic acidosis. J Clin Invest 107: 1563–1569, 2001.
 248. Laghmani K, Sakamoto A, Yanagisawa M, Preisig PA, Alpern RJ. A consensus sequence in the endothelin‐B receptor second intracellular loop is required for NHE3 activation by endothelin‐1. Am J Physiol Renal Physiol 288: F732–F739, 2005.
 249. Lanese DM, Yuan BH, McMurtry IF, Conger JD. Comparative sensitivities of isolated rat renal arterioles to endothelin. Am J Physiol 263: F894–F899, 1992.
 250. Largo R, Gomez‐Garre D, Liu XH, Alonso J, Blanco J, Plaza JJ, Egido J. Endothelin‐1 upregulation in the kidney of uninephrectomized spontaneously hypertensive rats and its modification by the angiotensin‐converting enzyme inhibitor quinapril. Hypertension 29: 1178–1185, 1997.
 251. Lemann J Jr, Litzow JR, Lennon EJ. The effects of chronic acid loads in normal man: Further evidence for the participation of bone mineral in the defense against chronic metabolic acidosis. J Clin Invest 45: 1608–1614, 1966.
 252. Lennon EJ, Lemann J Jr, Litzow JR. The effects of diet and stool composition on the net external acid balance of normal subjects. J Clin Invest 45: 1601–1607, 1966.
 253. Letizia C, Cerci S, De Ciocchis A, D'Ambrosio C, Scuro L, Scavo D. Plasma endothelin‐1 levels in normotensive and borderline hypertensive subjects during a standard cold pressor test. J Hum Hypertens 9: 903–907, 1995.
 254. Letizia C, Iannaccone A, Cerci S, Santi G, Cilli M, Coassin S, Pannarale MR, Scavo D. Circulating endothelin‐1 in non‐insulin‐dependent diabetic patients with retinopathy. Horm Metab Res 29: 247–251, 1997.
 255. Lev S, Moreno H, Martinez R, Canoll P, Peles E, Musacchio J, Plowman G, Rudy B, Schlessinger J. Protein tyrosine kinase PYK2 involved in Ca(2+)‐induced regulation of ion channel and MAP kinase functions. Nature 376: 737–745, 1995.
 256. Levine DZ. An in vivo microperfusion study of distal tubule bicarbonate reabsorption in normal and ammonium chloride rats. J Clin Invest 75: 588–595, 1985.
 257. Levine DZ. Single‐nephron studies: Implications for acid‐base regulation. Kidney Int 38: 744–761, 1990.
 258. Levine DZ, Iacovitti M, Buckman S, Harrison V. In vivo modulation of rat distal tubule net HCO3 flux by VIP, isoproterenol, angiotensin II, and ADH. Am J Physiol 266: F878–883, 1994.
 259. Levine DZ, Iacovitti M, Buckman S, Hincke MT, Luck B, Fryer JN. ANG II‐dependent HCO3− reabsorption in surviving rat distal tubules: Expression/activation of H(+)‐ATPase. Am J Physiol 272: F799–F808, 1997.
 260. Li JS, Knafo L, Turgeon A, Garcia R, Schiffrin EL. Effect of endothelin antagonism on blood pressure and vascular structure in renovascular hypertensive rats. Am J Physiol 271: H88–H93, 1996.
 261. Li JS, Schiffrin EL. Effect of chronic treatment of adult spontaneously hypertensive rats with an endothelin receptor antagonist. Hypertension 25: 495–500, 1995.
 262. 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.
 263. Lin H, Sangmal M, Smith MJ Jr, Young DB. Effect of endothelin‐1 on glomerular hydraulic pressure and renin release in dogs. Hypertension 21: 845–851, 1993.
 264. Liu W, Murcia NS, Duan Y, Weinbaum S, Yoder BK, Schwiebert E, Satlin LM. Mechanoregulation of intracellular Ca2+ concentration is attenuated in collecting duct of monocilium‐impaired orpk mice. Am J Physiol Renal Physiol 289: F978–F988, 2005.
 265. López‐Farré A, Gómez‐Garre D, Bernabeu F, Montanes I, Millas I, López‐Novoa JM. Renal effects and mesangial cell contraction induced by endothelin are mediated by PAF. Kidney Int 39: 624–630, 1991.
 266. Loutzenhiser K, Loutzenhiser R. Angiotensin II‐induced Ca(2+) influx in renal afferent and efferent arterioles: Differing roles of voltage‐gated and store‐operated Ca(2+) entry. Circ Res 87: 551–557, 2000.
 267. Loutzenhiser R, Chilton L, Trottier G. Membrane potential measurements in renal afferent and efferent arterioles: Actions of angiotensin II. Am J Physiol 273: F307–F314, 1997.
 268. Loutzenhiser R, Epstein M, Hayashi K, Horton C. Direct visualization of effects of endothelin on the renal microvasculature. Am J Physiol 258: F61–F68, 1990.
 269. Loutzenhiser R, Hayashi K, Epstein M. Divergent effects of KCl‐induced depolarization on afferent and efferent arterioles. Am J Physiol 257: F561–F564, 1989.
 270. MacDonald JA, Borman MA, Muranyi A, Somlyo AV, Hartshorne DJ, Haystead TA. Identification of the endogenous smooth muscle myosin phosphatase‐associated kinase. Proc Natl Acad Sci U S A 98: 2419–2424, 2001.
 271. Maddox DA, Horn JF, Famiano FC, Gennari FJ. Load dependence of proximal tubular fluid and bicarbonate reabsorption in the remnant kidney of the Munich‐Wistar rat. J Clin Invest 77: 1639–1649, 1986.
 272. Madeddu P, Troffa C, Glorioso N, Pazzola A, Soro A, Manunta P, Tonolo G, Demontis MP, Varoni MV, Anania V. Effect of endothelin on regional hemodynamics and renal function in awake normotensive rats. J Cardiovasc Pharmacol 14: 818–825, 1989.
 273. Majowicz MP, Gonzalez Bosc LV, Albertoni Borghese MF, Delgado MF, Ortiz MC, Sterin Speziale N, Vidal NA. Atrial natriuretic peptide and endothelin‐3 target renal sodium‐glucose cotransporter. Peptides 24: 1971–1976, 2003.
 274. Malatino LS, Bellanuova I, Cataliotti A, Cuzzola F, Mallamaci F, Tripepi G, Parlongo S, Cutrupi S, Mangiafico RA, Ferri C, Galletti F, Gloriso N, Strazzullo P, Zoccali C. Renal endothelin‐1 is linked to changes in urinary salt and volume in essential hypertension. J Nephrol 13: 178–184, 2000.
 275. Malnic G, Fernandez R, Cassola AC, Barreto‐Chaves ML, de Souza MO, Aires Mde M. Mechanisms and regulation of H+ transport in distal tubule epithelial cells. Wien Klin Wochenschr 109: 429–434, 1997.
 276. Malnic G, Fernandez R, Lopes MJ. The role of the distal nephron in the regulation of acid‐base equilibrium by the kidney. Braz J Med Biol Res 27: 831–850, 1994.
 277. Marchetti J, Meneton P, Lebrun F, Bloch‐Faure M, Rajerison RM. The parietal sheet of Bowman's capsule of rat renal glomerulus: A target of endothelin and PAF. Am J Physiol 268: F1053–F1061, 1995.
 278. Masaki T. Historical review: Endothelin. Trends Pharmacol Sci 25: 219–224, 2004.
 279. Masaki T, Kimura S, Yanagisawa M, Goto K. Molecular and cellular mechanism of endothelin regulation. Implications for vascular function. Circulation 84: 1457–1468, 1991.
 280. Matsumura Y, Nakase K, Ikegawa R, Hayashi K, Ohyama T, Morimoto S. The endothelium‐derived vasoconstrictor peptide endothelin inhibits renin release in vitro. Life Sci 44: 149–157, 1989.
 281. Matsuo G, Matsummura Y, Tadano K, Hashimoto T, Morimoto S. Effects of sarafotoxin S6c on renal haemodynamics and urine formation in anaesthetized dogs. Clin Exp Pharmacol Physiol 24: 487–491, 1997.
 282. Mattyus I, Zimmerhack LB, Schwarz A, Hentschel M, Brandis M, Milteny M, Tulassay T. Renal excretion of endothelin in children is influenced by age and diuresis. Acta Pædiatr 83: 468–472, 1994.
 283. Mawji IA, Robb GB, Tai SC, Marsden PA. Role of the 3′‐untranslated region of human endothelin‐1 in vascular endothelial cells. to transcript lability and the cellular heat shock response Contribution. J Biol Chem 279: 8655–8667, 2004.
 284. Migas I, Bäcker A, Meyer‐Lehnert H, Kramer HJ. Endothelin synthesis by porcine inner medullary collecting duct cells. Am J Hyperten 8: 748–752, 1995.
 285. Miller RL, Kohan DE. Hypoxia regulates endothelin‐1 production by the inner medullary collecting duct. J Lab Clin Med 131: 45–48, 1998.
 286. Modesti P, Cecioni I, Migliorini A, Naldoni A, Costoli A, Vanni S, Serneri G. Increased renal endothelin formation is associated with sodium retention and increased free water clearance. Am J Physiol 275: H1070–H1077, 1998.
 287. Modesti PA, Cecioni I, Costoli A, Poggesi L, Galanti G, Serneri GG. Renal endothelin in heart failure and its relation to sodium excretion. Am Heart J 140: 617–622, 2000.
 288. Moe O, Tejedor A, Campbell WB, Alpern R, Henrich WL. Effects of endothelin on in vitro renin secretion. Am J Physiol 260: E521–E525, 1991.
 289. Montero A, Rodriguez‐Barbero A, Lopez‐Novoa JM. A role for platelet‐activating factor in endothelin‐1‐induced rat mesangial cell proliferation. Eur J Pharmacol 243: 235–240, 1993.
 290. Morgera S, Schlenstedt J, Hambach P, Giessing M, Deger S, Hocher B, Neumayer H. Combined ETA/ETB receptor blockade of human peritoneal mesothelial cells inhibits collagen I RNA synthesis. Kidney Int 64: 2033–2040, 2003.
 291. Moridaira K, Nodera M, Sato G, Yanagisawa H. Detection of prepro‐ET‐1 mRNA in normal rat kidney by in situ RT‐PCR. Nephron Exp Nephrol 95: e55–e61, 2003.
 292. Morigi M, Buelli S, Angioletti S, Zanchi C, Longaretti L, Zoja C, Galbusera M, Gastoldi S, Mundel P, Remuzzi G, Benigni A. In response to protein load podocytes reorganize cytoskeleton and modulate endothelin‐1 gene: Implication for permselective dysfunction of chronic nephropathies. Am J Pathol 166: 1309–1320, 2005.
 293. Morigi M, Buelli S, Zanchi C, Longaretti L, Macconi D, Benigni A, Moioli D, Remuzzi G, Zoja C. Shigatoxin‐induced endothelin‐1 expression in cultured podocytes autocrinally mediates actin remodeling. Am J Pathol 169: 1965–1975, 2006.
 294. Morimoto T, Liu W, Woda C, Carattino MD, Wei Y, Hughey RP, Apodaca G, Satlin LM, Kleyman TR. Mechanism underlying flow stimulation of sodium absorption in the mammalian collecting duct. Am J Physiol Renal Physiol 291: F663–F669, 2006.
 295. Mortensen LH, Fink GD. Salt‐dependency of endothelin‐induced, chronic hypertension in conscious rats. Hypertension 19: 549–554, 1992.
 296. Nadler SP, Zimplemann JA, Hebert RL. Endothelin inhibits vasopressin‐stimulated water permeability in rat terminal inner medullary collecting duct. J Clin Invest 90: 1458–1466, 1992.
 297. Naess PA, Christensen G, Kiil F. Inhibitory effect of endothelin on renin release in dog kidneys. Acta Physiol Scand 148: 131–136, 1993.
 298. Nakano D, Pollock DM. Contribution of endothelin A receptors in endothelin 1‐dependent natriuresis in female rats. Hypertension 53: 324–330, 2009.
 299. Nakano D, Pollock JS, Pollock DM. Renal medullary ETB receptors produce diuresis and natriuresis via NOS1. Am J Physiol Renal Physiol 294: F1205–F1211, 2008.
 300. Nambi P, Pullen M, Wu H, Aiyar N, Ohlstein EH, Edwards RM. Identification of endothelin receptor subtypes in human renal cortex and medulla using subtypes‐selective ligands. Endocrinology 131: 1081–1086, 1992.
 301. Nambi P, Wu HL, Pullen M, Aiyar N, Bryan H, Elliott J. Identification of endothelin receptor subtypes in rat kidney cortex using subtype‐selective ligands. Mol Pharmacol 42: 336–339, 1992.
 302. Naruse M, Uchida S, Ogata E, Kurokawa K. Endothelin‐1 increases cell calcium in mouse collecting tubule cells. Am J Physiol 261: F720–F725, 1991.
 303. Navar L, Arendshorst W, Pallone T, Inscho E, Imig J, Bell P. The Renal Microcirculation. In: Tuma RF, Duran WN, Ley K, editors. Handbook of Physiology, Microcirculation. San Diego: Elsevier, 2008, p. 550–683.
 304. Neuser D, Zaiss S, Stasch J. Endothelin receptors in cultured renal epithelial cells. Eur J Pharmacol 176: 241–243, 1990.
 305. Nir A, Clavell AL, Heublein D, Aarhus LL, Burnett JCJ. Acute hypoxia and endogenous renal endothelin. J Am Soc Nephrol 4: 1920–1924, 1994.
 306. Nobiling R, Buhrle CP, Hackenthal E, Helmchen U, Steinhausen M, Whalley A, Taugner R. Ultrastructure, renin status, contractile and electrophysiological properties of the afferent glomerular arteriole in the rat hydronephrotic kidney. Virchows Arch A Pathol Anat Histopathol 410: 31–42, 1986.
 307. Nussdorfer GG, Rossi GP, Belloni AS. The role of endothelins in the paracrine control of the secretion and growth of the adrenal cortex. Int Rev Cytol 171: 267–308, 1997.
 308. Ohta K, Hirata Y, Imai T, Kanno K, Emori T, Shichiri M, Marumo F. Cytokine‐induced release of endothelin‐1 from porcine renal epithelial cell line. Biochem Biophys Res Commun 169: 578–584, 1990.
 309. Oishi R, Nonoguchi H, Tomita K, Marumo F. Endothelin‐1 inhibits AVP‐stimulated osmotic water permeability in rat medullary collecting duct. Am J Physiol 261: F951–F956, 1991.
 310. Oishi S, Sasaki M, Sato T. Elevated immunoreactive endothelin levels in patients with pheochromocytoma. Am J Hypertens 7: 717–722, 1994.
 311. Omatsu S, Tomoyoshi T. Immunohistochemical study on endothelin in rat kidney. Hinyokika Kiyo 43: 109–114, 1997.
 312. Ominato M, Satoh T, Katz AI. Endothelins inhibit Na‐K‐ATPase activity in proximal tubules: Studies of mechanisms. J Am Soc Nephrol 5: 588, 1994.
 313. 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.
 314. Ong ACM, Jowett TP, Firth JD, Burton S, Karet FE, Fine LG. An endothelin‐1 mediated autocrine growth loop involved in human renal tubular regeneration. Kidney Int 48: 390–401, 1995.
 315. Orth SR, Amann K, Gehlen F, Unger L, Wagner J, Raschack M, Ritz E. Adult human mesangial cells (HMCs) express endothelin‐B‐receptors which mediate endothelin‐1‐induced cell growth. J Cardiovasc Pharmacol 36: S232–S237, 2000.
 316. Ortiz PA, Garvin JL. Role of nitric oxide in the regulation of nephron transport. Am J Physiol Renal Physiol 282: F777–F784, 2002.
 317. Otsuka A, Mikami H, Katahira K, Tsunetoshi T, Minamitani K, Ogihara T. Changes in plasma renin activity and aldosterone concentration in response to endothelin injection in dogs. Acta Endocrinol (Copenh) 121: 361–364, 1989.
 318. Owada A, Tomita K, Terada Y, Sakamoto H, Nonguchi H, Marumo F. Endothelin (ET)‐3 stimulates cyclic guanosine 3′,5′‐monophosphate production via ETB receptor by producing nitric oxide in isolated rat glomerulus, and in cultured rat mesangial cells. J Clin Invest 93: 556–563, 1994.
 319. Oyekan A, Balazy M, McGiff JC. Renal oxygenases: Differential contribution to vasoconstriction induced by ET‐1 and ANG II. Am J Physiol 273: R293–R300, 1997.
 320. Ozaki S, Ihara M, Saeki T, Fukami T, Ishikawa K, Yano M. Endothelin ETB receptors couple to two distinct signaling pathways in porcine kidney epithelial LLC‐PK1 cells. J Pharmacol Exp Ther 270: 1035–1040, 1994.
 321. Ozawa Y, Hasegawa T, Tsuchiya K, Yoshizumi M, Tamaki T. Effect of endothelin‐1 (1‐31) on the renal resistance vessels. J Med Invest 50: 87–94, 2003.
 322. Pallone TL, Zhang Z, Rhinehart K. Physiology of the renal medullary microcirculation. Am J Physiol Renal Physiol 284: F253–F266, 2003.
 323. Pavlov TS, Chahdi A, Ilatovskaya DV, Levchenko V, Vandewalle A, Pochynyuk O, Sorokin A, Staruschenko A. Endothelin‐1 inhibits the epithelial Na+ channel through betaPix/14‐3‐3/Nedd4‐2. J Am Soc Nephrol 21: 833–843, 2010.
 324. 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.
 325. Pernow J, Franco‐Cereceda A, Matran R, Lundberg JM. Effect of endothelin‐1 on regional vascular resistances in the pig. J Cardiovasc Pharmacol 13(Suppl 5): S205–S206, 1989.
 326. Pfitzer G. Invited review: Regulation of myosin phosphorylation in smooth muscle. J Appl Physiol 91: 497–503, 2001.
 327. Phisitkul S, Hacker C, Simoni J, Tran RM, Wesson DE. Dietary protein causes a decline in the glomerular filtration rate of the remnant kidney mediated by metabolic acidosis and endothelin receptors. Kidney Int 73: 192–199, 2008.
 328. Phisitkul S, Khanna A, Simoni J, Broglio K, Sheather S, Rajab MH, Wesson DE. Amelioration of metabolic acidosis in patients with low GFR reduced kidney endothelin production and kidney injury, and better preserved GFR. Kidney Int 77: 617–623.
 329. Plato C, Garvin J. Nitric oxide, endothelin and nephron transport: Potential interactions. Clin Exp Pharmacol Physiol 26: 262–268, 1999.
 330. Plato C, Pollock D, Garvin J. Endothelin inhibits thick ascending limb chloride flux via ETB receptor‐mediated NO release. Am J Physiol 279: F326–F333, 2000.
 331. Pollock DM. Renal endothelin in hypertension. Curr Opin Nephrol Hypertens 9: 157–164, 2000.
 332. Pollock DM, Jenkins JM, Cook AK, Imig JD, Inscho EW. L‐type calcium channels in the renal microcirculatory response to endothelin. Am J Physiol Renal Physiol 288: F771–F777, 2005.
 333. Pollock DM, Opgenorth TJ. Comparison of the hemodynamic effects of endothelin‐1 and big endothelin‐1 in the rat. Biochem Biophys Res Commun 179: 1122–1126, 1991.
 334. Pollock DM, Opgenorth TJ. Evidence for endothelin‐induced renal vasoconstriction independent of ETA receptor activation. Am J Physiol 264: R222–R226, 1993.
 335. Pollock DM, Opgenorth TJ. ETA receptor‐mediated responses to endothelin‐1 and big endothelin‐1 in the rat kidney. Br J Pharmacol 111: 729–732, 1994.
 336. Pollock DM, Pollock JS. Evidence for endothelin involvement in the response to high salt. Am J Physiol Renal Physiol 281: F144–F150, 2001.
 337. Praetorius H, Spring K. The renal cell primary cilium functions as a flow sensor. Curr Opin Nephrol Hypertens 12: 517–520, 2003.
 338. Praetorius HA, Spring KR. Bending the MDCK cell primary cilium increases intracellular calcium. J Membr Biol 184: 71–79, 2001.
 339. Preisig PA. The acid‐activated signaling pathway: Starting with Pyk2 and ending with increased NHE3 activity. Kidney Int 72: 1324–1329, 2007.
 340. Preisig PA, Ives HE, Cragoe EJ Jr, Alpern RJ, Rector FC Jr. Role of the Na+/H +antiporter in rat proximal tubule bicarbonate absorption. J Clin Invest 80: 970–978, 1987.
 341. Pupilli C, Brunori M, Misciglia N, Selli C, Ianni L, Yanagisawa M, Mannelli M, Serio M. Presence and distribution of endothelin‐1 gene expression in human kidney. Am J Physiol 267: F679–F687, 1994.
 342. Pupilli C, Romagnani P, Lasagni L, Bellini F, Misciglia N, Emoto N, Yanagisawa M, Rizzo M, Mannelli M, Serio M. Localization of endothelin‐converting enzyme‐1 in human kidney. Am J Physiol 273: F749–F756, 1997.
 343. Qiu C, Baylis C. Endothelin and angiotensin mediate most glomerular responses to nitric oxide inhibition. Kidney Int 55: 2390–2396, 1999.
 344. Qiu C, Samsell L, Baylis C. Actions of endogenous endothelin on glomerular hemodynamics in the rat. Am J Physiol 269: R469–R473, 1995.
 345. Rabelink TJ, Kaasiager KAH, Boer P, Stroes EG, Braam B, Koomans HA. Effects of endothelin‐1 on renal function in humans: Implications for physiology and pathophysiology. Kidney Int 46: 376–381, 1994.
 346. Rajagopalan S, Laursen JB, Borthayre A, Kurz S, Keiser J, Haleen S, Giaid A, Harrison DG. Role for endothelin‐1 in angiotensin II‐mediated hypertension. Hypertension 30: 29–34, 1997.
 347. Rajapakse NW, Oliver JJ, Evans RG. Nitric oxide in responses of regional kidney blood flow to vasoactive agents in anesthetized rabbits. J Cardiovasc Pharmacol 40: 210–219, 2002.
 348. Rakugi H, Nakamaru M, Saito H, Higaki J, Ogihara T. Endothelin inhibits renin release from isolated rat glomeruli. Biochem Biophys Res Commun 155: 1244–1247, 1988.
 349. Rascher W, Gyodi G, Worgall S, Sulyok E. Effect of sodium chloride supplementation on urinary sodium excretion in premature infants. J Pediatr 125: 793–797, 1994.
 350. Rebibou JM, He CJ, Delarue F, Peraldi MN, Adida C, Rondeau E, Sraer JD. Functional endothelin‐1 receptors on human glomerular podocytes and mesangial cells. Nephrol Dial Transplant 7: 288–292, 1992.
 351. Redmond EM, Cahill PA, Hodges R, Zhang S, Sitzmann JV. Regulation of endothelin receptors by nitric oxide in cultured rat vascular smooth muscle cells. J Cell Physiol 166: 469–479, 1996.
 352. Redmond EM, Cahill PA, Sitzmann JV. Flow‐mediated regulation of endothelin receptors in cocultured vascular smooth muscle cells: An endothelium‐dependent effect. J Vasc Res 34: 425–435, 1997.
 353. Remer T. Influence of nutrition on acid‐base balance–metabolic aspects. Eur J Nutr 40: 214–220, 2001.
 354. Remuzzi G. Role of endothelin in the development of glomerulosclerosis. Kidney Blood Press Res 19: 182–183, 1996.
 355. Ren Y, Garvin JL, Liu R, Carretero OA. Crosstalk between the connecting tubule and the afferent arteriole regulates renal microcirculation. Kidney Int 71: 1116–1121, 2007.
 356. Resink TJ, Hahn AW, Scott‐Burden T, Powell J, Weber E, Buhler FR. Inducible endothelin mRNA expression and peptide secretion in cultured human vascular smooth muscle cells. Biochem Biophys Res Commun 168: 1303–1310, 1990.
 357. Riggleman A, Harvey J, Baylis C. Endothelin mediates some of the renal actions of acutely administered angiotensin II. Hypertension 38: 105–109, 2001.
 358. Ritthaler T, Della Bruna R, Kramer BK, Kurtz A. Endothelins inhibit cyclic‐AMP induced renin gene expression in cultured mouse juxtaglomerular cells. Kidney Int 50: 108–115, 1996.
 359. Ritthaler T, Scholz H, Ackermann M, Riegger G, Kurtz A, Kramer BK. Effects of endothelins on renin secretion from isolated mouse renal justaglomerular cells. Am J Physiol 268: F39–F45, 1995.
 360. Roczniak A, Burns KD. Nitric oxide stimulates guanylate cyclase and regulates sodium transport in rabbit proximal tubule. Am J Physiol 270: F106–F115, 1996.
 361. Rodriguez‐Pascual F, Redondo‐Horcajo M, Magan‐Marchal N, Lagares D, Martinez‐Ruiz A, Kleinert H, Lamas S. Glyceraldehyde‐3‐phosphate dehydrogenase regulates endothelin‐1 expression by a novel, redox‐sensitive mechanism involving mRNA stability. Mol Cell Biol 28: 7139–7155, 2008.
 362. 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.
 363. Rossi GP, Belloni AS, Nussdorfer GG, Pessina AC. Endothelin‐1 and the adrenal gland. J Cardiovasc Pharmacol 35: S17–S20, 2000.
 364. Rossi NF. Effect of endothelin‐3 on vasopressin release in vitro and water excretion in vivo in Long‐Evans rats. J Physiol 461: 501–511, 1993.
 365. Rossi NF. Regulation of vasopressin secretion by ETA and ETB receptors in compartmentalized rat hypothalamo‐neurohypophysial explants. Am J Physiol Endocrinol Metab 286: E535–E541, 2004.
 366. Rossi NF, O'Leary DS, Scislo TJ, Caspers ML, Chen H. Central endothelin 1 regulation of arterial pressure and arginine vasopressin secretion via the AV3V region. Kidney Int Suppl 61: S22–S26, 1997.
 367. Rufanova VA, Alexanian A, Wakatsuki T, Lerner A, Sorokin A. Pyk2 mediates endothelin‐1 signaling via p130Cas/BCAR3 cascade and regulates human glomerular mesangial cell adhesion and spreading. J Cell Physiol 219: 45–56, 2009.
 368. Rufanova VA, Sorokin A. CrkII associates with BCAR3 in response to endothelin‐1 in human glomerular mesangial cells. Exp Biol Med (Maywood) 231: 752–756, 2006.
 369. Rúiz‐Ortega M, Gómez‐Garre D, Alcázar R, Palacios I, Bustos C, González S, Plaza JJ, González E, Egido J. Involvement of angiotensin II and endothelin in matrix protein production and renal sclerosis. J Hypertension 12: 551–558, 1994.
 370. Ruskoaho H, Leskinen H, Magga J, Taskinen P, Mantymaa P, Vuolteenaho O, Leppaluoto J. Mechanisms of mechanical load‐induced atrial natriuretic peptide secretion: Role of endothelin, nitric oxide, and angiotensin II. J Mol Med 75: 876–885, 1997.
 371. Russell FD, Davenport AP. Secretory pathways in endothelin synthesis. Br J Pharmacol 126: 391–398, 1999.
 372. Russell FD, Skepper JN, Davenport AP. Human endothelial cell storage granules: A novel intracellular site for isoforms of the endothelin‐converting enzyme. Circ Res 83: 314–321, 1998.
 373. Ryan MJ, Black TA, Millard SL, Gross KW, Hajduczok G. Endothelin‐1 increases calcium and attenuates renin gene expression in As4.1 cells. Am J Physiol Heart Circ Physiol 283: H2458–H2465, 2002.
 374. Saito I, Mizuno K, Niimura S, Fukuchi S. Urinary endothelin and sodium excretion in essential hypertension. Nephron 65: 152–153, 1993.
 375. Saito M, Homma S, Yamatsu I, Sato M, Ohshima N. Visualization of renal microcirculation in isolated Munich‐Wistar rat kidneys: Effects of endothelin‐1 on renal hemodynamic activity. Jap J Pharmacol 66: 221–229, 1994.
 376. 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.
 377. Sakamoto H, Sasaki S, Nakamura Y, Fushimi K, Marumo F. Regulation of endothelin‐1 production in cultured rat mesangial cells. Kidney Int 41: 350–355, 1992.
 378. Sarkis A, Lopez B, Roman RJ. Role of 20‐hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids in hypertension. Curr Opin Nephrol Hypertens 13: 205–214, 2004.
 379. Schambelan M, Sebastian A, Katuna BA, Arteaga E. Adrenocortical hormone secretory response to chronic NH4Cl‐induced metabolic acidosis. Am J Physiol 252: E454–E460, 1987.
 380. Schiffrin EL, Touyz RM. Vascular biology of endothelin. J Cardiovasc Pharmacol 32(Suppl 3): S2–S13, 1998.
 381. Schneider MP, Ge Y, Pollock DM, Pollock JS, Kohan DE. Collecting duct‐derived endothelin regulates arterial pressure and Na excretion via nitric oxide. Hypertension 51: 1605–1610, 2008.
 382. Schneider MP, Inscho EW, Pollock DM. Attenuated vasoconstrictor responses to endothelin in afferent arterioles during a high‐salt diet. Am J Physiol Renal Physiol 292: F1208–F1214, 2007.
 383. Schnermann J, Lorenz JN, Briggs JP, Keiser JA. Induction of water diuresis by endothelin in rats. Am J Physiol 263: F516–F526, 1992.
 384. Schnermann JB, Zhu XL, Shu X, Yang T, Huang YG, Kretzler M, Briggs JP. Regulation of endothelin production and secretion in cultured collecting duct cells by endogenous transforming growth factor‐β. Endocrinol 137: 5000–5008, 1996.
 385. Scholz H, Kramer BK, Hamann M, Gotz KH, Kurtz A. Effects of endothelins on renin secretion from rat kidneys. Acta Physiol Scand 155: 173–182, 1995.
 386. Schramek H, Gstraunthaler G, Willinger CC, Pfaller W. Hyperosmolality regulates endothelin release by Madin‐Darby canine kidney cells. J Am Soc Nephrol 4: 206–213, 1993.
 387. Schramek H, Willinger CC, Gstraunthaler G, Pfaller W. Endothelin‐3 modulates glomerular filtration rate in the isolated perfused rat kidney. Renal Physiol Biochem 15: 325–333, 1992.
 388. Schricker K, Scholz H, Hamann M, Clozel M, Kramer BK, Kurtz A. Role of endogenous endothelins in the renin system of normal and two‐kidney, one clip rats. Hypertension 25: 1025–1029, 1995.
 389. Schroeder AC, Imig JD, LeBlanc EA, Pham BT, Pollock DM, Inscho EW. Endothelin‐mediated calcium signaling in preglomerular smooth muscle cells. Hypertension 35: 280–286, 2000.
 390. Schuster VL. Cyclic adenosine monophosphate‐stimulated bicarbonate secretion in rabbit cortical collecting tubules. J Clin Invest 75: 2056–2064, 1985.
 391. Schweda F, Friis U, Wagner C, Skott O, Kurtz A. Renin release. Physiology (Bethesda) 22: 310–319, 2007.
 392. Schweizer A, Valdenaire O, Nelbock P, Deuschle U, Dumas Milne Edwards JB, Stumpf JG, Loffler BM. Human endothelin‐converting enzyme (ECE‐1): Three isoforms with distinct subcellular localizations. Biochem J 328(Pt 3): 871–877, 1997.
 393. Seney FD Jr, Marver D. Protein intake and cation transport in the loop of Henle. J Lab Clin Med 114: 587–594, 1989.
 394. Serneri GGN, 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.
 395. Shi H, Asher C, Chigaev A, Yung Y, Reuveny E, Seger R, Garty H. Interactions of beta and gamma ENaC with Nedd4 can be facilitated by an ERK‐mediated phosphorylation. J Biol Chem 277: 13539–13547, 2002.
 396. 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. Hypertens 15: 493–496, 1990.
 397. Shimada K, Takahashi M, Ikeda M, Tanzawa K. Identification and characterization of two isoforms of an endothelin‐converting enzyme‐1. FEBS Lett 371: 140–144, 1995.
 398. Shyamala V, Moulthrop THM, Stratton‐Thomas J, Tekamp‐Olson P. Two distinct human endothelin B receptors generated by alternative splicing from a single gene. Cell Mol Biol Res 40: 285–296, 1994.
 399. Silldorff EP, Yang S, Pallone TL. Prostaglandin E2 abrogates endothelin‐induced vasoconstriction in renal outer meduillary descending vasa recta of the rat. J Clin Invest 95: 2734–2740, 1995.
 400. Silver RB, Mennitt PA, Satlin LM. Stimulation of apical H‐K‐ATPase in intercalated cells of cortical collecting duct with chronic metabolic acidosis. Am J Physiol 270: F539–F547, 1996.
 401. Simonson M, Dunn MJ. Endothelin‐1 stimulates contraction of rat glomerular mesangial cells and potentiates b‐adrenergic‐mediated cyclic adenosine monophosphate accumulation. J Clin Invest 85: 790–797, 1990.
 402. Simonson MS. Endothelins: Multifunctional renal peptides. Physiol Rev 73: 375–411, 1993.
 403. Simonson MS, Dunn MJ. Cellular signaling by peptides of the endothelin gene family. FASEB J 4: 2989–3000, 1990.
 404. Simonson MS, Dunn MJ. Ca2+ signaling by distinct endothelin peptides in glomerular mesangial cells. Exp Cell Res 192: 148–156, 1991.
 405. Simonson MS, Rooney A. Characterization of endothelin receptors in mesangial cells: Evidence for two functionally distinct endothelin binding sites. Mol Pharmacol 46: 41–50, 1994.
 406. Simonson MS, Wann S, Mene P, Dubyak GR, Kester M, Dunn MJ. Endothelin‐1 activates the phosphoinositide cascade in cultured glomerular mesangial cells. J Cardiovasc Pharmacol 13: S80–83; discussion S84, 1989.
 407. Simonson MS, Wann S, Mene P, Dubyak GR, Kester M, Nakazato Y, Sedor JR, Dunn MJ. Endothelin stimulates phospholipase C, Na/H exchange, c‐fos expression, and mitogenesis in rat mesangial cells. J Clin Invest 83: 708–712, 1989.
 408. Siroky BJ, Ferguson WB, Fuson AL, Xie Y, Fintha A, Komlosi P, Yoder BK, Schwiebert EM, Guay‐Woodford LM, Bell PD. Loss of primary cilia results in deregulated and unabated apical calcium entry in ARPKD collecting duct cells. Am J Physiol Renal Physiol 290: F1320–F1328, 2006.
 409. Somlyo AP, Somlyo AV. Signal transduction by G‐proteins, Rho‐kinase and protein phosphatase to smooth muscle and non‐muscle myosin II. J Physiol 522 (Pt 2): 177–185, 2000.
 410. Sørensen 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.
 411. Sorokin A, Kohan DE. Physiology and pathology of endothelin‐1 in renal mesangium. Am J Physiol Renal Physiol 285: F579–F589, 2003.
 412. Sorokin A, Kozlowski P, Graves L, Philip A. Protein‐tyrosine kinase Pyk2 mediates endothelin‐induced p38 MAPK activation in glomerular mesangial cells. J Biol Chem 276: 21521–21528, 2001.
 413. Steinhausen M, Endlich K. Controversies on glomerular filtration from Ludwig to the present. Pflugers Arch 432: R73–R81, 1996.
 414. Strait KA, Stricklett PK, Kohan DE. Altered collecting duct adenylyl cyclase content in collecting duct endothelin‐1 knockout mice. BMC Nephrol 8: 8, 2007.
 415. Strait KA, Stricklett PK, Kohan JL, Miller MB, Kohan DE. Calcium regulation of endothelin‐1 synthesis in rat inner medullary collecting duct. Am J Physiol Renal Physiol 293: F601–F606, 2007.
 416. Stricklett PK, Hughes AK, Kohan DE. Endothelin‐1 stimulates NO production and inhibits cAMP accumulation in rat inner medullary collecting duct through independent pathways. Am J Physiol Renal Physiol 290: F1315–F1319, 2006.
 417. Stricklett PK, Strait KA, Kohan DE. Novel mechanism for regulation of endothelin synthesis: Role of extracellular pH. Cell Physiol Biochem 21: 117–122, 2008.
 418. Sudo N, Kamoi K, Ishibashi M, Yamaji T. Plasma endothelin‐1 and big endothelin‐1 levels in women with pre‐eclampsia. Acta Endocrinol (Copenh) 129: 114–120, 1993.
 419. Sugimoto T, Haneda M, Sawano H, Isshiki K, Maeda S, Koya D, Inoki K, Yasuda H, Kashiwagi A, Kikkawa R. Endothelin‐1 induces cyclooxygenase‐2 expression via nuclear factor of activated T‐cell transcription factor in glomerular mesangial cells. J Am Soc Nephrol 12: 1359–1368, 2001.
 420. Sugiura M, Snajdar RM, Schwartzberg M, Badr KF, Inagami T. Identification of two types of specific endothelin receptors in rat mesangial cell. Biochem Biophys Res Commun 162: 1396–1401, 1989.
 421. Sullivan JC, Goodchild TT, Cai Z, Pollock DM, Pollock JS. Endothelin(A) (ET(A)) and ET(B) receptor‐mediated regulation of nitric oxide synthase 1 (NOS1) and NOS3 isoforms in the renal inner medulla. Acta Physiol (Oxf) 191: 329–336, 2007.
 422. Sullivan JC, Wang B, Boesen EI, D'Angelo G, Pollock JS, Pollock DM. Novel use of ultrasound to examine regional blood flow in the mouse kidney. Am J Physiol Renal Physiol 297: F228–F235, 2009.
 423. Tack I, Marin Castano E, Pecher C, Praddaude F, Bascands JL, Bompart G, Ader JL, Girolami JP. Endothelin increases NO‐dependent cGMP production in isolated glomeruli but not in mesangial cells. Am J Physiol 272: F31–F39, 1997.
 424. Tahara A, Tsukada J, Tomura Y, Suzuki T, Yatsu T, Shibasaki M. Effect of YM218, a nonpeptide vasopressin V(1A) receptor‐selective antagonist, on rat mesangial cell hyperplasia and hypertrophy. Vascul Pharmacol 46: 463–469, 2007.
 425. Takabatake T, Ise T, Ohta K, Kobayashi K. Effects of endothelin on renal hemodynamics and tubuloglomerular feedback. Am J Physiol 263: F103–F108, 1992.
 426. Takagi M, Matsuoka H, Atarashi K, Yagi S. Endothelin: A new inhibitor of renin release. Biochem Biophys Res Commun 157: 1164–1168, 1988.
 427. Takagi M, Tsukada H, Matsuoka H, Yagi S. Inhibitory effect of endothelin on renin release in vitro. Am J Physiol 257: E833–E838, 1989.
 428. Takeda M, Breyer MD, Noland TD, Homma T, Hoover RL, Inagami T, Kon V. Endothelin‐1 receptor antagonist: Effects on endothelin‐ and cyclosporine‐treated mesangial cells. Kidney Int 42: 1713–1719, 1992.
 429. Takeda M, Iwasaki S, Hellings SE, Yoshida H, Homma T, Kon V. Divergent expression of EtA and EtB receptors in response to cyclosporine in mesangial cells. Am J Pathol 144: 473–479, 1994.
 430. Takemoto F, Uchida S, Katagirl H, Oka Y, Nakao A, Kurokawa K. Desensitization of endothelin‐1 binding by vasopressin via a cAMP‐mediated pathway in rat CCD. Am J Physiol 268: F385–F390, 1995.
 431. Takemoto F, Uchida S, Ogata E, Kurokawa K. Endothelin‐1 and endothelin‐3 binding to rat nephrons. Am J Physiol 264: F827–F832, 1993.
 432. Takenaka T, Epstein M, Forster H, Landry DW, Iijima K, Goligorsky MS. Attenuation of endothelin effects by a chloride channel inhibitor, indanyloxyacetic acid. Am J Physiol 262: F799–F806, 1992.
 433. Takenaka T, Forster H, Epstein M. Protein kinase C and calcium channel activation as determinants of renal vasoconstriction by angiotensin II and endothelin. Circ Res 73: 743–750, 1993.
 434. Tamas P, Worgall S, Sulyok E, Rascher W. Renal electrolyte and water handling in normal pregnancy: Possible role of endothelin‐1. Eur J Obstet Gynecol Reprod Biol 55: 89–95, 1994.
 435. Taniguchi J, Tsuruoka S, Mizuno A, Sato J, Fujimura A, Suzuki M. TRPV4 as a flow sensor in flow‐dependent K+ secretion from the cortical collecting duct. Am J Physiol Renal Physiol 292: F667–F673, 2007.
 436. Taylor TA, Gariepy CE, Pollock DM, Pollock JS. Gender differences in ET and NOS systems in ETB receptor‐deficient rats: Effect of a high salt diet. Hypertension 41: 657–662, 2003.
 437. Teitelbaum I, Berl T. Increased cytosolic Ca2+ inhibits AVP‐stimulated adenylyl cyclase activity in rat IMCT cells by activation of PKC. Am J Physiol 266: F486–F490, 1994.
 438. Telemaque‐Potts S, Kuc RE, Maguire JJ, Ohlstein E, Yanagisawa M, Davenport AP. Elevated systemic levels of endothelin‐1 and blood pressure correlate with blunted constrictor responses and downregulation of endothelin(A), but not endothelin(B), receptors in an animal model of hypertension. Clin Sci (Lond) 103(Suppl 48): 357S–362S, 2002.
 439. Terada Y, Tomita K, Nonoguchi H, Marumo F. Different localization of two types of endothelin receptor mRNA in microdissected rat nephron segments using reverse transcription and polymerase chain reaction assay. J Clin Invest 90: 107–112, 1992.
 440. Terada Y, Tomita K, Nonoguchi H, Yang T, Marumo F. Different localization and regulation of two types of vasopressin receptor messenger RNA in microdissected rat nephron segments using reverse transcription polymerase chain reaction. J Clin Invest 92: 2339–2345, 1993a.
 441. Terada Y, Tomita K, Nonoguchi H, Yang T, Marumo F. Expression of endothelin‐3 mRNA along rat nephron segments using polymerase chain reaction. Kidney Int 44: 1273–1280, 1993b.
 442. Terada Y, Yamada T, Takayama M, Nonoguchi H, Sasaki S, Tomita K, Marumo F. Presence and regulation of Raf‐1‐K (Kinase), MAPK‐K, MAP‐K, and S6‐K in rat nephron segments. J Am Soc Nephrol 6: 1565–1577, 1995.
 443. Thai TL, Arendshorst WJ. ADP‐ribosyl cyclase and ryanodine receptors mediate endothelin ETA and ETB receptor‐induced renal vasoconstriction in vivo. Am J Physiol Renal Physiol 295: F360–F368, 2008.
 444. Thai TL, Churchill GC, Arendshorst WJ. NAADP receptors mediate calcium signaling stimulated by endothelin‐1 and norepinephrine in renal afferent arterioles. Am J Physiol Renal Physiol 297: F510–F516, 2009.
 445. Tharaux PL, Dussaule JC, Pauti MD, Vassitch Y, Ardaillou R, Chatziantoniou C. Activation of renin synthesis is dependent on intact nitric oxide production. Kidney Int 51: 1780–1787, 1997.
 446. Todd‐Turla KM, Chen M, Kretzler M, Rose D, Smart A, Yu T, Zhu X, Fehes‐Toth G, Briggs JP, Schnermann J. Synthesis and polarized secretion of endothelin in a cortical collecting duct cell line (M1). Hypertens 24: 408, 1994.
 447. Todd‐Turla KM, Zhu XL, Shu X, Chen M, Yu T, Smart A, Killen PD, Fejes‐Toth G, Briggs JP, Schnermann JB. Synthesis and secretion of endothelin in a cortical collecting duct cell line. Am J Physiol 271: F330–F339, 1996.
 448. Tomita K, Nonoguchi H, Marumo F. Effects of endothelin on peptide‐dependent cyclic adenosine monophosphate accumulation along the nephron segments of the rat. J Clin Invest 85: 2014–2018, 1990.
 449. Tomita K, Nonoguchi H, Marumo F. Inhibition of Fluid Transport by Endothelin through Protein Kinase C in Collecting Duct of Rats. Basel: Karger, 1991.
 450. Tomita K, Nonoguchi H, Terada Y, Marumo F. Effects of ET‐1 on water and chloride transport in cortical collecting ducts of the rat. Am J Physiol 264: F690–F696, 1993.
 451. Touyz RM, Lariviere R, Schiffrin EL. Endothelin influences pHi of human platelets through protein kinase C mediated pathways. Thromb Res 78: 55–65, 1995.
 452. Treiber FA, Jackson RW, Davis H, Pollock JS, Kapuku G, Mensah GA, Pollock DM. Racial differences in endothelin‐1 at rest and in response to acute stress in adolescent males. Hypertension 35: 722–725, 2000.
 453. Tsuruoka S, Schwartz GJ. Adaptation of rabbit cortical collecting duct HCO3− transport to metabolic acidosis in vitro. J Clin Invest 97: 1076–1084, 1996.
 454. Tsuruoka S, Schwartz GJ, Wakaumi M, Nishiki K, Yamamoto H, Purkerson JM, Fujimura A. Nitric oxide production modulates cyclosporin A‐induced distal renal tubular acidosis in the rat. J Pharmacol Exp Ther 305: 840–845, 2003.
 455. Tsuruoka S, Watanabe S, Purkerson JM, Fujimura A, Schwartz GJ. Endothelin and nitric oxide mediate adaptation of the cortical collecting duct to metabolic acidosis. Am J Physiol Renal Physiol 291: F866–F873, 2006.
 456. Turner AJ, Murphy LJ. Molecular pharmacology of endothelin converting enzymes. Biochem Pharm 51: 91–102, 1996.
 457. Uchida S, Horie M, Yanagisawa M, Matsushita Y, Kurokawa K, Ogata E. Polarized secreton of endothelin‐1 and big ET‐1 in MDCK cells is inhibited by cell Na+ flux and disrupted by NH4Cl. J Cardiovasc Pharmacol 17(Suppl 7): S226–S228, 1991.
 458. 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.
 459. 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.
 460. Uzuner K, Banks RO. Endothelin‐induced natriuresis and diuresis are pressure‐dependent events in the rat. Am J Physiol 265: R90–R96, 1993.
 461. Valdenaire O, Lepailleur‐Enouf D, Egidy G, Thouard A, Barret A, Vranckx R, Tougard C, Michel JB. A fourth isoform of endothelin‐converting enzyme (ECE‐1) is generated from an additional promoter molecular cloning and characterization. Eur J Biochem 264: 341–349, 1999.
 462. Vassileva I, Mountain C, Pollock DM. Functional role of ETB receptors in the renal medulla. Hypertension 41: 1359–1363, 2003.
 463. Vijayaraghavan J, Scicli AG, Carretero OA, Slaughter C, Moomaw C, Hersh LB. The hydrolysis of endothelins by neutral endopeptidase 24.11 (enkephalinase). J Biol Chem 265: 14150–14155, 1990.
 464. Vio CP, Figueroa CD, Caorsi I. Anatomical relationship between kallikrein‐containing tubules and the juxtaglomerular apparatus in the human kidney. Am J Hypertens 1: 269–271, 1988.
 465. Vogel V, Backer A, Heller J, Kramer HJ. The renal endothelin system in the Prague hypertensive rat, a new model of spontaneous hypertension. Clin Sci 97: 91–98, 1999.
 466. Wagner CA, Giebisch G, Lang F, Geibel JP. Angiotensin II stimulates vesicular H+‐ATPase in rat proximal tubular cells. Proc Natl Acad Sci U S A 95: 9665–9668, 1998.
 467. Wagner OF, Christ G, Wojita J, Vierhapper H, Parzer S, Nowotny PJ, Schneider B, Waldhäusl W, Binder BR. Polar secretion of endothelin‐1 by cultured endothelial cells. J Biol Chem 267: 16066–16068, 1992.
 468. Walshe T, Ferguson G, Connell P, O'Brien C, Cahill P. Pulsatile flow increases the expression of eNOS, ET‐1, and prostacyclin in a novel in vitro cocultrue model of the retinal vasculature. Invest Opthalmol Vis Sci 46: 375–382, 2005.
 469. Walter R, Helmle‐Kolb C, Forgo J, Binswanger U, Murer H. Stimulation of Na/H exchange activity by endothelin in opossum kidney cells. Pflügers Arch 430: 137–144, 1995.
 470. Wang H, Sakurai K, Endoh M. Pharmacological analysis by HOE642 and KB‐R9032 of the role of Na(+)/H(+) exchange in the endothelin‐1‐induced Ca(2+) signalling in rabbit ventricular myocytes. Br J Pharmacol 131: 638–644, 2000.
 471. Wang T. Nitric oxide regulates HCO3− and Na+ transport by a cGMP‐mediated mechanism in the kidney proximal tubule. Am J Physiol 272: F242–F248, 1997.
 472. Wang T, Hropot M, Aronson PS, Giebisch G. Role of NHE isoforms in mediating bicarbonate reabsorption along the nephron. Am J Physiol Renal Physiol 281: F1117–F1122, 2001.
 473. Wang Y, Mishra R, Simonson M. Ca(2+)/Calmodulin‐Dependent Protein Kinase II Stimulates c‐fos Transcription and DNA Synthesis by a Src‐Based Mechanism in Glomerular Mesangial Cells. J Am Soc Nephrol 14: 28–36, 2003.
 474. Warner TD, Allcock GH, Vane JR. Reversal of established responses to endothelin‐1 in vivo and in vitro by the endothelin receptor antagonists, BQ‐123 and PD 145065. Br J Pharmacol 112: 207–213, 1994.
 475. Webb ML, Dickinson KE, Delaney CL, Liu EC, Serafino R, Cohen RB, Monshizadegan H, Moreland S. The endothelin receptor antagonist, BQ‐123, inhibits angiotensin II‐induced contractions in rabbit aorta. Biochem Biophys Res Commun 185: 887–892, 1992.
 476. Weber MA, Black H, Bakris G, Krum H, Linas S, Weiss R, Linseman JV, Wiens BL, Warren MS, Lindholm LH. A selective endothelin‐receptor antagonist to reduce blood pressure in patients with treatment‐resistant hypertension: A randomised, double‐blind, placebo‐controlled trial. Lancet 374: 1423–1431, 2009.
 477. Weinberger MH, Miller JZ, Luft FC, Grim CE, Fineberg NS. Definitions and characteristics of sodium sensitivity and blood pressure resistance. Hypertension 8: II127–II134, 1986.
 478. Weiner ID, Frank AE, Wingo CS. Apical proton secretion by the inner stripe of the outer medullary collecting duct. Am J Physiol 276: F606–F613, 1999.
 479. Weinstein AM. A mathematical model of rat distal convoluted tubule. I. Cotransporter function in early DCT. Am J Physiol Renal Physiol 289: F699–F720, 2005.
 480. Wellings RP, Corder R, Doherty AM, Vane JR. Antagonism of renal and systemic responses to endothelin‐1 infusion with PD 145065. Eur J Pharmacol 256: 201–204, 1994.
 481. 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.
 482. Wenzel RR, Ruthemann J, Bruck H, Schafers RF, Michel MC, Philipp T. Endothelin‐A receptor antagonist inhibits angiotensin II and noradrenaline in man. Br J Clin Pharmacol 52: 151–157, 2001.
 483. Wesson D. Endogenous endothelins mediate increased distal tubule acidification induced by dietray acid in rats. J Clin Invest 99: 2203–2211, 1997.
 484. Wesson D, Dolson G. Endothelin‐1 increases rat distal tubule acidification in vivo. Am J Physiol 273: F586–F594, 1997.
 485. Wesson DE. Augmented bicarbonate reabsorption by both the proximal and distal nephron maintains chloride‐deplete metabolic alkalosis in rats. J Clin Invest 84: 1460–1469, 1989.
 486. Wesson DE. Combined K+ and Cl− repletion corrects augmented H+ secretion by distal tubules in chronic alkalosis. Am J Physiol 266: F592–F603, 1994.
 487. Wesson DE. Reduced bicarbonate secretion mediates increased distal tubule acidification induced by dietary acid. Am J Physiol 271: F670–F678, 1996.
 488. Wesson DE. Dietary acid increases blood and renal cortical acid content in rats. Am J Physiol 274: F97–F103, 1998a.
 489. Wesson DE. Na/H exchange and H‐K ATPase increase distal tubule acidification in chronic alkalosis. Kidney Int 53: 945–951, 1998b.
 490. Wesson DE. Endogenous endothelins mediate increased acidification in remnant kidneys. J Am Soc Nephrol 12: 1826–1835, 2001.
 491. Wesson DE, Dolson GM. Augmented bidirectional HCO3 transport by rat distal tubules in chronic alkalosis. Am J Physiol 261: F308–F317, 1991.
 492. Wesson DE, Nathan T, Rose T, Simoni J, Tran RM. Dietary protein induces endothelin‐mediated kidney injury through enhanced intrinsic acid production. Kidney Int 71: 210–217, 2007.
 493. Wesson DE, Simoni J. Increased tissue acid mediates a progressive decline in the glomerular filtration rate of animals with reduced nephron mass. Kidney Int 75: 929–935, 2009.
 494. Wesson DE, Simoni J, Prabhakar S. Endothelin‐induced increased nitric oxide mediates augmented distal nephron acidification as a result of dietary protein. J Am Soc Nephrol 17: 406–413, 2006.
 495. Wilkes BM, Susin M, Mento PF, Macica CM, Giraldi EP, Boss E, Nord EP. Localization of endothelin‐like immunoreactivity in rat kidneys. Am J Physiol 260: F913–F920, 1991.
 496. Williams JM, Pollock DM. Contribution of prostanoid tp receptors to the pressor and intrarenal haemodynamic response to endothelin. Clin Exp Pharmacol Physiol 33: 253–257, 2006.
 497. Wong NL, Tsui JK. Angiotensin regulates endothelin‐B receptor in rat inner medullary collecting duct. Metabolism 50: 661–666, 2001.
 498. Wong NL, Wong BP, Tsui JK. Vasopressin regulates endothelin‐B receptor in rat inner medullary collecting duct. Am J Physiol Renal Physiol 278: F369–F374, 2000.
 499. Wong S, Brennan FE, Young MJ, Fuller PJ, Cole TJ. A direct effect of aldosterone on endothelin‐1 gene expression in vivo. Endocrinology 148: 1511–1517, 2007.
 500. Wong WH, Wong BP, Wong EF, Huang MH, Wong NL. Downregulation of endothelin B receptors in cardiomyopathic hamsters. Cardiology 89: 195–201, 1998.
 501. Woodcock E, Land S. Endothelin receptors in rat renal papilla with a high affinity for endothelin‐3. Eur J Pharmacol 208: 255–260, 1991.
 502. Woodcock EA, Land SL. Functional endothelin ETB receptors on renal papillary tubules. Eur J Pharmacol 247: 93–95, 1993.
 503. Worgall S, Manz F, Kleschin K, Feth F, Rascher W. Elevated urinary excretion of endothelin‐like immunoreactivity in children with renal disease is related to urine flow rate. Clin Nephrol 41: 331–337, 1994.
 504. Wu L, Gao X, Brown RC, Heller S, O'Neil RG. Dual role of the TRPV4 channel as a sensor of flow and osmolality in renal epithelial cells. Am J Physiol Renal Physiol 293: F1699–F1713, 2007.
 505. Wu‐Wong JR, Dayton BD, Opgenorth TJ. Endothelin‐1‐evoked arachidonic acid release: A Ca(2+)‐dependent pathway. Am J Physiol 271: C869–C877, 1996.
 506. Xu D, Emoto N, Giaid A, Slaughter C, Kaw S, deWit D, Yanagisawa M. ECE‐1: A membrane‐bound metalloprotease that catalyzes the proteolytic activation of big endothelin‐1. Cell 78: 473–485, 1994.
 507. Yamamoto T, Hirohama T, Uemura H. Endothelin B receptor‐like immunoreactivity in podocytes of the rat kidney. Arch Histol Cytol 65: 245–250, 2002.
 508. 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.
 509. 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.
 510. Yamashita K, Discher D, Hu J, Bishopric N, Webster K. Molecular regulation of the endothelin‐1 gene by hypoxia. Contributions of hypoxia‐inducible factor‐1, activator protein‐1, GATA‐2, AND p300/CBP. J Biol Chem 276: 12645–12653, 2001.
 511. Yanagisawa H, Hammer RE, Richardson JA, Emoto N, Williams SC, Takeda S‐i, Clouthier DE, Yanagisawa M. Disruption of ECE‐1 and ECE‐2 reveals a role for endothelin‐converting enzyme‐2 in murine cardiac development. J Clin Invest 105: 925–933, 2000.
 512. 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.
 513. Yang T, Terada Y, Nonoguchi H, Ujiie K, Tomita K, Marumo F. Effect of hyperosmolality on production and mRNA expression of endothelin‐1 in inner medullary collecting duct. Am J Physiol 264: F684–F689, 1993.
 514. Yard BA, Chorianopoulos E, Herr D, Van Der Woude FJ. Regulation of endothelin‐1 and transforming growth factor‐beta1 production in cultured proximal tubular cells by albumin and heparan sulphate glycosaminoglycans. Nephrol Dial Transplant 16: 1769–1775, 2001.
 515. Ye Q, Chen S, Gardner DG. Endothelin inhibits NPR‐A and stimulates eNOS gene expression in rat IMCD cells. Hypertension 41: 675–681, 2003.
 516. Yokokawa K, Kohno M, Johchi M, Horio T, Murakawa K, Yasunari K, Yanagisawa M, Takeda T. Effect of endothelin receptor antagonist, BQ‐123, on Ca2+ signaling in cultured rat mesangial cells. Life Sci 53: 1631–1641, 1993.
 517. Yu C, Yang Z, Ren H, Zhang Y, Han Y, He D, Lu Q, Wang X, Yang C, Asico LD, Hopfer U, Eisner GM, Jose PA, Zeng C. D(3) dopamine receptor regulation of ETB receptors in renal proximal tubule cells from WKY and SHRs. Am J Hypertens 22: 877–833, 2009.
 518. Yukimura T, Notoya M, Mizojiri K, Mizuhira V, Matsuura T, Ebara T, Miura K, Kim S, Iwao H, Song K. High resolution localization of endothelin receptors in rat renal medulla. Kidney Int 50: 135–147, 1996.
 519. Yukimura T, Yamashita Y, Miura K, Kim S, Iwao H, Takai M, Okada T. Renal vasodilating and diuretic actions of a selective endothelin ETB receptor agonist, IRL1620. Eur J Pharmacol 264: 399–405, 1994.
 520. Zeidel ML, Brady HR, Kone BC, Gullans SR, Brenner BM. Endothelin, a peptide inhibitor of Na+‐K+‐ATPase in intact tubular epithelial cells. Am J Physiol 257: C1101–C1107, 1989.
 521. Zeiler M, Löffler B‐M, Bock HA, Thiel G, Basel K. Water diuresis increases endothelin‐1 excretion in humans. J Am Soc Nephrol 6: 751, 1995.
 522. Zeng C, Asico LD, Yu C, Villar VA, Shi W, Luo Y, Wang Z, He D, Liu Y, Huang L, Yang C, Wang X, Hopfer U, Eisner GM, Jose PA. Renal D3 dopamine receptor stimulation induces natriuresis by endothelin B receptor interactions. Kidney Int 74: 750–759, 2008.
 523. Zeng C, Hopfer U, Asico LD, Eisner GM, Felder RA, Jose PA. Altered AT1 receptor regulation of ETB receptors in renal proximal tubule cells of spontaneously hypertensive rats. Hypertension 46: 926–931, 2005.
 524. Zeng C, Wang Z, Asico LD, Hopfer U, Eisner GM, Felder RA, Jose PA. Aberrant ETB receptor regulation of AT receptors in immortalized renal proximal tubule cells of spontaneously hypertensive rats. Kidney Int 68: 623–631, 2005.
 525. Zhang W, Xia X, Reisenauer MR, Rieg T, Lang F, Kuhl D, Vallon V, Kone BC. Aldosterone‐induced Sgk1 relieves Dot1a‐Af9‐mediated transcriptional repression of epithelial Na+ channel alpha. J Clin Invest 117: 773–783, 2007.
 526. Zhao X, Imig JD. Kidney CYP450 enzymes: Biological actions beyond drug metabolism. Curr Drug Metab 4: 73–84, 2003.
 527. Zoccali C, Leonardis D, Parlongo S, Mallamaci F, Postorino M. Urinary and plasma endothelin 1 in essential hypertension and in hypertension secondary to renoparenchymal disease. Nephrol Dial Transplant 10: 1320–1323, 1995.
 528. Zoja C, Morigi M, Figliuzzi M, Bruzzi I, Oldroyd S, Benigni A, Ronco P, Remuzzi G. Proximal tubular cell synthesis and secretion of endothelin‐1 on challenge with albumin and other proteins. Am J Kid Dis 26: 934–941, 1995.
 529. Zoja C, Orisio S, Perico N, Benigni A, Morigi M, Benatti L, Rambaldi A, Remuzzi G. Constitutive expression of endothelin gene in cultured human mesangial cells and its modulation by transforming growth factor‐β,thrombin, and a thromboxane A2 analogue. Lab Invest 64: 16–20, 1991.

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Article Title: Physiology of Endothelin and the Kidney
 

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Donald E. Kohan, Edward W. Inscho, Donald Wesson, David M. Pollock. Physiology of Endothelin and the Kidney. Compr Physiol 2011, 1: 883-919. doi: 10.1002/cphy.c100039