Endothelin
2003; American Physiological Society; Volume: 285; Issue: 2 Linguagem: Inglês
10.1152/ajpregu.00249.2003
ISSN1522-1490
Autores Tópico(s)Renin-Angiotensin System Studies
ResumoIN FOCUSEndothelinJoey P. GrangerJoey P. GrangerUniversity of Mississippi Medical Center, Jackson, Mississippi 39216Published Online:01 Aug 2003https://doi.org/10.1152/ajpregu.00249.2003MoreSectionsPDF (53 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat in 1988, yanagisawa and coworkers (55) characterized an endothelium-derived vasoconstrictor, a 21-amino acid peptide subsequently called endothelin (ET). ET-1 is derived from a 203-amino acid peptide precursor, preproendothelin, which is cleaved after translation to form proendothelin. In the presence of a converting enzyme located within the endothelial cells, proendothelin, or big ET, is cleaved to produce the 21-amino acid peptide. Various aspects of the ET system have been addressed by recent publications in the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology and other journals. Articles include investigations on cardiac (4, 16, 25, 30, 37, 48), vascular (29, 35, 38, 42, 44, 52), renal (1, 56, 8, 9, 13, 19, 26, 39, 43), pulmonary (52), reproductive (28), fetal (11, 12, 29, 52), and neuroendocrine (9, 10, 25, 47, 56) systems. Although much attention has been given to the role of ET in the pathophysiology of cardiovascular and renal disease acting via an ET type A (ETA) receptor, more recent studies indicate an important physiological role for ET in the regulation of sodium balance and arterial pressure, via an ET type B (ETB) receptor.Increased synthesis of ET has been reported in various diseases associated with cardiovascular abnormalities such as hypertension, diabetes, cardiac hypertrophy, congestive heart failure, and chronic renal failure (1, 3, 7, 9, 20–22, 40, 43–45). ET receptor binding sites have been identified throughout the body, with the greatest numbers of receptors in the kidneys and lungs (22, 45). Although the biochemical and molecular nature of ET has been well characterized, the physiological importance of ET in the regulation of renal and cardiovascular function in normal disease processes remains to be an important area of investigation. ETA receptors are primarily located on vascular smooth muscle cells. These receptors are involved in mediating ET-1 vasoconstriction and cellular proliferation in various disease states (22, 44). ETB receptors are located on multiple cell types in the brain, on vascular endothelial cells, and renal epithelial cells (8, 17, 18, 22, 23, 26, 31, 53). Although the location and the signal transduction pathways for ETB receptors have been well characterized, the physiological role of these receptors has not been fully elucidated. The ETB receptors appear to play a role as clearance receptors, removing ET from the circulation and interstitial spaces (22). A significant role for ETB receptors in the development of enteric neurons and melanocytes has also been established (13). Loss of ETB receptors results in failure of melanocytes and enteric neurons to develop, resulting in abnormal development of the gastrointestinal tract and megacolon (13). Activation of vascular ETB receptors by ET-1 or other ligands results in vasodilation; however, the physiological importance of ETB-mediated vasodilatation is still unclear.Although ETA receptors play an important role in mediating the vascular abnormalities that occur in certain forms of hypertension (especially salt-sensitive hypertension), these receptors do not appear to influence cardiovascular and renal function under normal physiological conditions. Indeed, several laboratories have reported that chronic ETA receptor blockade has no significant long-term effect on kidney function or arterial pressure regulation in normal rats (1, 2, 7, 20). However, this may not be the case for all species (6).Recent studies published in this journal have suggested an important interaction between ET and the renin-angiotensin system. Angiotensin II plays an important role in the regulation of arterial pressure during various physiological and pathophysiological conditions, such as hypertension, congestive heart failure, and chronic renal diseases (41). Angiotensin II is thought to influence renal and cardiovascular function through its direct renal vasoconstrictor, sodium-retaining, mitogenic, and pro-oxidant actions (41). Studies have also suggested that angiotensin II may exert its physiological actions via interaction with autacoid factors such as ET (1, 3–5). Consistent with this suggestion are results of several recent studies indicating that the renal and hypertensive effects of angiotensin II can be markedly attenuated or completely abolished by ETA receptor antagonists (1, 3–5, 40, 43). The quantitative importance of ET in mediating the chronic hypertensive actions of angiotensin II may depend on the level of dietary sodium intake (3)Several lines of evidence support a role for angiotensin II as a regulator of ET synthesis. Angiotensin II is a potent stimulator of ET release by cultured endothelial, smooth muscle, and renal mesangial cells (4, 5). Furthermore, angiotensin II stimulates expression of preproendothelin mRNA in cultured cells such as endothelial and vascular smooth muscle. Evidence supporting an effect of angiotensin II on synthesis of ET in vivo is not as abundant. Barton and colleagues (4) recently reported enhanced ET levels in renal tissue, but not myocardial tissue, in rats with chronic angiotensin II hypertension. More recent experiments by Alexander et al. (1) and others (43) have reported angiotensin II-induced expression of preproendothelin RNA or ET protein levels in kidneys. Thus angiotensin II may exert its chronic physiological actions via stimulation of ET and activation of ETA receptors.ET has also been implicated in regulating vascular function during normal pregnancy. Both renal blood flow and glomerular filtration increases by over 25% during pregnancy. Renal vascular resistance decreases significantly during pregnancy. Moreover, the myogenic reactivity of small renal arteries from pregnant rats is significantly reduced (13, 33). Conrad and colleagues (13, 33) recently provided convincing evidence that ET acting through the endothelial ETB receptor and the nitric oxide pathway accounts for the renal vasodilation and reduced myogenic reactivity of small renal vessels during pregnancy in rats. They also recently provided important evidence that this pathway is stimulated during pregnancy by the hormone relaxin (32, 46).ET is also involved in regulating vascular function during the pregnancy disorder preeclampsia. Preeclampsia is associated with hypertension, proteinuria, and endothelial dysfunction (21). Because endothelial damage is a known stimulus for ET synthesis, increases in the production of ET and activation of ETA receptors may participate in the pathophysiology of preeclampsia (21). Plasma concentration of ET has been measured in a number of studies involving normal pregnant women and women with preeclampsia. Most investigators have found higher ET plasma concentrations of approximately two- to threefold in women with preeclampsia. Typically, plasma levels of ET are highest during the latter stage of the disease, suggesting that ET may not be involved in the initiation of preeclampsia, but rather in the progression of disease into a malignant phase. Although the elevation in plasma levels of ET during preeclampsia is only two or threefold above normal, previous studies have reported that this level of plasma ET can have significant long-term effects on systemic hemodynamics and arterial pressure regulation (54). Thus long-term elevations in plasma levels of ET comparable to those measured in women with preeclampsia could play a role in mediating the reductions in renal function and elevations in arterial pressure observed in women with preeclampsia.Although most studies have reported no significant changes in circulating levels of ET during moderate forms of preeclampsia, a role for ET as a paracrine or autocrine agent in preeclampsia remains worthy of consideration (21). Alexander et al. (2) recently examined the role of ET in mediating the hypertension in response to chronic reductions in uterine perfusion pressure in conscious, chronically instrumented pregnant rats. Using an RNase protection assay, they found that renal expression of preproendothelin was significantly elevated in both the medulla and the cortex of the pregnant rats with chronic reductions in uterine perfusion pressure compared with control pregnant rats. Moreover, they reported that chronic administration of the selective ETA receptor antagonist markedly attenuated the increase in mean arterial pressure in pregnant rats with chronic reductions in uterine perfusion pressure. In sharp contrast to the response in reduced uterine perfusion pressure rats, ETA receptor blockade had no significant effect on blood pressure in the normal pregnant animal (2). These findings suggest that ET plays a major role in mediating the hypertension produced by chronic reductions in uterine perfusion pressure in pregnant rats. Despite this important finding, the mechanism linking enhanced renal production of ET to chronic reductions in uterine pressure in pregnant rats or in preeclamptic women is unknown. One potential mechanism for enhanced ET production is via transcriptional regulation of the ET-1 gene by tumor necrosis factor (TNF)-α (21). TNF-α is elevated in preeclamptic women and has been implicated in the disease process (21). Another potential stimulus for ET production during preeclampsia is activation of the angiotensin type 1 receptor. As noted above, studies from various laboratories have found that angiotensin II, via the angiotensin type 1 receptor, is a potent stimulator for ET production. More importantly, ET plays a critical role in mediating the long-term renal and hypertensive action of angiotensin II in rats (55). Thus the role of factors such as TNF-α and angiotensin type 1 receptor activation in mediating the increased synthesis of ET in preeclampsia remains to be determined.There is growing evidence to suggest that ET-1, acting through the ETB receptors, is involved in the regulation of sodium balance under normal physiological conditions. The kidney is an important site of ET-1 production, and ETB receptors are expressed at important renal sites of ET synthesis, particularly in the renal medulla (8, 9, 17, 22–24, 31, 49, 51, 53). Some of the first studies using synthetic ET-1 demonstrated that nonpressor doses of ET-1 produced significant natriuresis and diuresis (22, 45). It is now known that ETB receptors are located in various parts of the nephron, including the proximal tubule, medullary thick ascending limb, collecting tubule, and the inner medullary collecting duct (8, 17, 18, 22–24). The highest concentration of ETB receptors appears to be on the inner medullary collecting duct in the renal medulla. Activation of ETB receptors has been reported to inhibit sodium and water reabsorption along various parts of the nephron. Taken together, these data indicate that ET-1, via ETB receptors, may influence the renal handling of sodium and water.For the renal ET system to be an important control system for the regulation of sodium balance, the production of renal ET should change in response to variations in sodium intake. Moreover, blockade of ETB receptors should result in a salt-sensitive form of hypertension. Although there are ample data showing that ET-1 can influence sodium reabsorption, there is a paucity of data in the literature examining the relationship between sodium intake and renal production of ET-1. A recent study by Pollock and Pollock (39), however, has shown a positive correlation between sodium intake and renal excretion of ET. The most convincing evidence for a role of the renal ET in controlling sodium excretion and arterial pressure during chronic changes in sodium intake are the results of studies by Gariepy et al. (14), Pollock and Pollock (39), and Ohuchi et al. (34). Gariepy and colleagues demonstrated that rats deficient in ETB receptor expression display salt-sensitive hypertension. Likewise, Pollock and Pollock reported that chronic pharmacological blockade of the ETB receptor in rats resulted in hypertension that was very sensitive to dietary sodium intake. Moreover, Ohuchi et al. reported elevation in blood pressure by genetic and pharmacological disruption of the ETB receptor in mice. Although these studies support an important role for the renal ET system in controlling sodium excretion, additional experiments are necessary to not only define the link between sodium intake and renal ET synthesis, but also to understand the tubular and hemodynamic mechanisms whereby ETB receptor activation regulates renal sodium handling. References 1 Alexander BT, Cockrell KL, Rinewalt AN, Herrington JN, and Granger JP. Enhanced renal expression of preproendothelin mRNA during chronic angiotensin II hypertension. Am J Physiol Regul Integr Comp Physiol 280: R1388–R1392, 2001.Link | ISI | Google Scholar2 Alexander BT, Rinewalt AN, Cockrell KL, Bennett WA, and Granger JP. Endothelin-A receptor blockade attenuates the hypertension in response to chronic reductions in uterine perfusion pressure. Hypertension 37: 485–489, 2001.Crossref | PubMed | ISI | Google Scholar3 Ballew JR and Fink GD. Role of ETA receptors in experimental ANG II-induced hypertension in rats. Am J Physiol Regul Integr Comp Physiol 281: R150–R154, 2001.Link | ISI | Google Scholar4 Barton M, Shaw S, d'Uscio LV, Moreau P, and Luscher TF. Differential modulation of the renal and myocardial endothelin system by angiotensin II in vivo. J Cardiovasc Pharmacol 31: S265–S268, 1998.Crossref | PubMed | ISI | Google Scholar5 Barton M, Shaw S, d'Uscio LV, Moreau P, and Luscher TF. Angiotensin II increases vascular and renal endothelin-1 and functional endothelin converting enzyme activity in vivo: role of ETA receptors for endothelin regulation. Biochem Biophys Res Commun 238: 861–865, 1997.Crossref | PubMed | ISI | Google Scholar6 Boemke W, Hocher B, Schleyer N, Krebs MO, and Kaczmarczyk G. Hemodynamic, renal, and endocrine responses to acute ETA blockade at different ANG II plasma levels. Am J Physiol Regul Integr Comp Physiol 280: R1322–R1331, 2001.Link | ISI | Google Scholar7 D'Uscio LV, Moreau P, Shaw S, Takase H, Barton M, and Luscher TF. Effects of chronic ETA-receptor blockade in angiotensin II-induced hypertension. Hypertension 29: 435–441, 1997.Crossref | PubMed | ISI | Google Scholar8 Dean R, Zhuo J, Alcorn D, Casley D, and Mendelson FAO. Cellular localization of endothelin receptor subtypes in the rat kidney following in vitro labeling. Clin Exp Pharmacol Physiol 23: 524–531, 1996.Crossref | PubMed | ISI | Google Scholar9 Deng LY, Day R, and Schiffrin EL. Localization of sites of enhanced expression of endothelin-1 in the kidney of DOCA-salt hypertensive rats. J Am Soc Nephrol 7: 1158–1164, 1996.Crossref | PubMed | ISI | Google Scholar10 Di Nunzio AS, Jaureguiberry MS, Rodano V, Bianciotti LG, and Vatta MS. Endothelin-1 and -3 diminish neuronal NE release through an NO mechanism in rat anterior hypothalamus. Am J Physiol Regul Integr Comp Physiol 283: R615–R622, 2002.Link | ISI | Google Scholar11 Docherty CC, Kalmar-Nagy J, Engelen M, and Nathanielsz PW. Development of fetal vascular responses to endothelin-1 and acetylcholine in the sheep. Am J Physiol Regul Integr Comp Physiol 280: R554–R562, 2001.Link | ISI | Google Scholar12 Docherty CC, Kalmar-Nagy J, Engelen M, Koenen SV, Nijland M, Kuc RE, Davenport AP, and Nathanielsz PW. Effect of in vivo fetal infusion of dexamethasone at 0.75 GA on fetal ovine resistance artery responses to ET-1. Am J Physiol Regul Integr Comp Physiol 281: R261–R268, 2001.Link | ISI | Google Scholar13 Gandley RE, Conrad KP, and McLaughlin MK. Endothelin and nitric oxide mediate reduced myogenic reactivity of small renal arteries from pregnant rats. Am J Physiol Regul Integr Comp Physiol 280: R1–R7, 2001.Link | ISI | Google Scholar14 Gariepy CE, Ohuchi T, Williams SC, Richardson JA, and Yanagisawa M. Salt-sensitive hypertension in endothelin-B receptor-deficient rats. J Clin Invest 105: 925–933, 2000.Crossref | PubMed | ISI | Google Scholar15 Gariepy CE, Cass DT, and Yanagisawa M. Null mutation of endothelin receptor type B gene in spotting lethal rats causes aganglionic megacolon and white coat color. Proc Natl Acad Sci USA 93: 867–872, 1996.Crossref | PubMed | ISI | Google Scholar16 Iemitsu M, Miyauchi T, Maeda S, Sakai S, Kobayashi T, Fujii N, Miyazaki H, Matsuda M, and Yamaguchi I. Physiological and pathological cardiac hypertrophy induce different molecular phenotypes in the rat. Am J Physiol Regul Integr Comp Physiol 281: R2029–R2036, 2001.Link | ISI | Google Scholar17 Jones CR, Hiley CR, Pelton JT, and Miller RC. Autoradiographic localization of endothelin binding sites in kidney. Eur J Pharmacol 163: 379–382, 1989.Crossref | PubMed | ISI | Google Scholar18 Karet FE, Kuc RE, and Davenport AP. Novel ligands BQ123 and BQ3020 characterize endothelin receptor subtypes ETA and ETB in human kidney. Kidney Int 44: 36–42, 1993.Crossref | PubMed | ISI | Google Scholar19 Kassab S, Novak J, Miller T, Kirchner K, and Granger J. Role of endothelin in mediating the attenuated renal hemodynamics in Dahl salt-sensitive hypertension. Hypertension 30: 682–686, 1997.Crossref | PubMed | ISI | Google Scholar20 Kassab S, Miller M, Novak J, Reckelhoff J, Clower B, and Granger JP. Endothelin-A receptor antagonism attenuates the hypertension and renal injury in Dahl salt-sensitive rats. Hypertension 31: 397–402, 1998.Crossref | PubMed | ISI | Google Scholar21 Khalil RA and Granger JP. Vascular mechanisms of increased arterial pressure in preeclampsia: lessons from animal models. Am J Physiol Regul Integr Comp Physiol 283: R29–R45, 2002.Link | ISI | Google Scholar22 Kohan D. Endothelins in the normal and diseased kidney. Am J Kidney Dis 29: 2–26, 1997.Crossref | PubMed | ISI | Google Scholar23 Kohzuki M, Johnston CI, Chai SY, Casley DJ, and Mendelsohn FAO. Localization and endothelin receptors in the rat kidney. Eur J Pharmacol 160: 193–194, 1989.Crossref | PubMed | ISI | Google Scholar24 Koseki C, Imai M, Hirata Y, Yanagisawa M, and Masaki T. Binding sites for endothelin-1 in rat tissues: an autoradiographic study (Abstract). J Cardiovasc Pharmacol 13, Suppl 5: S153–S154, 1989.Google Scholar25 Liu JL, Pliquett RU, Brewer E, Cornish KG, Shen YT, and Zucker IH. Chronic endothelin-1 blockade reduces sympathetic nerve activity in rabbits with heart failure. Am J Physiol Regul Integr Comp Physiol 280: R1906–R1913, 2001.Link | ISI | Google Scholar26 Michel H, Backer A, Meyer-Lehnert H, Migas I, and Kramer H. Rat renal, aortic and pulmonary endothelin-1 receptors: effects of changes in sodium and water intake. Clin Sci (Colch) 85: 593–597, 1993.Crossref | Google Scholar27 Miller DS, Masereeuw R, and Karnaky KJ Jr. Regulation of MRP2-mediated transport in shark rectal salt gland tubules. Am J Physiol Regul Integr Comp Physiol 282: R774–R781, 2002.Link | ISI | Google Scholar28 Mills TM, Pollock DM, Lewis RW, Branam HS, and Wingard CJ. Endothelin-1-induced vasoconstriction is inhibited during erection in rats. Am J Physiol Regul Integr Comp Physiol 281: R476–R483, 2001.Link | ISI | Google Scholar29 Molnar J, Nijland MJ, Howe DC, and Nathanielsz PW. Evidence for microvascular dysfunction after prenatal dexamethasone at 0.7, 075, and 08 gestation in sheep. Am J Physiol Regul Integr Comp Physiol 283: R561–R567, 2002.Link | ISI | Google Scholar30 Moser L, Faulhaber J, Wiesner RJ, and Ehmke H. Predominant activation of endothelin-dependent cardiac hypertrophy by norepinephrine in rat left ventricle. Am J Physiol Regul Integr Comp Physiol 282: R1389–R1394, 2002.Link | ISI | Google Scholar31 Nambi P, Pullen M, Wu HL, Aiyar N, Ohlstein EH, and Edwards RM. Identification of endothelin receptor subtypes in human renal cortex and medulla using subtype-selective ligands. Endocrinology 131: 1081–1086, 1992.Crossref | PubMed | ISI | Google Scholar32 Novak J, Danielson LA, Kerchner LJ, Sherwood OD, Ramirez RJ, Moalli PA, and Conrad KP. Relaxin is essential for renal vasodilation during pregnancy in conscious rats. J Clin Invest 107: 1469–1475, 2001.Crossref | PubMed | ISI | Google Scholar33 Novak J, Ramirez RJ, Gandley RE, Sherwood OD, and Conrad KP. Myogenic reactivity is reduced in small renal arteries isolated from relaxin-treated rats. Am J Physiol Regul Integr Comp Physiol 283: R349–R355, 2002.Link | ISI | Google Scholar34 Ohuchi T, Kuwaki T, Ling G, Dweit D, Ju K, Onodera M, Cao W, Yanagisawa M, and Kumada M. Elevation of blood pressure by genetic and pharmacological disruption of the ETB receptor in mice. Am J Physiol Regul Integr Comp Physiol 276: R1071–R1077, 1999.Link | ISI | Google Scholar35 Pang CY, Xu H, Huang N, Forrest CR, Perreault TM, and Neligan PC. Amplification effect and mechanism of action of ET-1 in U-46619-induced vasoconstriction in pig skin. Am J Physiol Regul Integr Comp Physiol 280: R713–R720, 2001.Link | ISI | Google Scholar36 Peterson TV, Emmeluth C, and Bie P. Renal effects of nitric oxide synthase inhibition in conscious water-loaded dogs. Am J Physiol Regul Integr Comp Physiol 281: R584–R590, 2001.Link | ISI | Google Scholar37 Piuhola J, Hammes A, Schuh K, Neyses L, Vuolteenaho O, and Ruskoaho H. Overexpression of sarcolemmal calcium pump attenuates induction of cardiac gene expression in response to ET-1. Am J Physiol Regul Integr Comp Physiol 281: R699–R705, 2001.Link | ISI | Google Scholar38 Platzack B, Wang Y, Crossley D, Lance V, Hicks JW, and Conlon JM. Characterization and cardiovascular actions of endothelin-1 and endothelin-3 from the American alligator. Am J Physiol Regul Integr Comp Physiol 282: R594–R602, 2002.Link | ISI | Google Scholar39 Pollock DM and Pollock JS. Evidence for endothelin involvement in the response to high salt. Am J Physiol Renal Physiol 281: F144–F150, 2001.Link | ISI | Google Scholar40 Rajagopalan S, Laursen JB, Borthayre A, Kurz S, Keiser J, Haleen S, Giaid A, and Harrison DG. Role for endothelin-1 in angiotensin II-mediated hypertension. Hypertension 30: 29–34, 1997.Crossref | PubMed | ISI | Google Scholar41 Reckelhoff JF and Romero JC. Role of oxidative stress in angiotensin-induced hypertension. Am J Physiol Regul Integr Comp Physiol 284: R893–R912, 2003.Link | ISI | Google Scholar42 Sandgaard NC, Andersen JL, Holstein-Rathlou NH, and Bie P. Aortic blood flow subtraction: an alternative method for measuring total renal blood flow in conscious dogs. Am J Physiol Regul Integr Comp Physiol 282: R1528–R1535, 2002.Link | ISI | Google Scholar43 Sasser JM, Pollock JS, and Pollock DM. Renal endothelin in chronic angiotensin II hypertension. Am J Physiol Regul Integr Comp Physiol 283: R243–R248, 2002.Link | ISI | Google Scholar44 Schiffrin EL. Endothelin: potential role in hypertension and vascular hypertrophy. Hypertension 25: 1135–1143, 1995.Crossref | PubMed | ISI | Google Scholar45 Simonson MS and Dunn MJ. Endothelin peptides and the kidney. Annu Rev Physiol 55: 249–265, 1993.Crossref | PubMed | ISI | Google Scholar46 Skott O and Carter AM. Relaxin is a vasodilator. Am J Physiol Regul Integr Comp Physiol 283: R347–R348, 2002.Link | ISI | Google Scholar47 Stocker SD, Stricker EM, and Sved AF. Acute hypertension inhibits thirst stimulated by ANG II, hyperosmolality, or hypovolemia in rats. Am J Physiol Regul Integr Comp Physiol 280: R214–R224, 2001.Link | ISI | Google Scholar48 Suzuki T and Miyauchi T. A novel pharmacological action of ET-1 to prevent the cytotoxicity of doxorubicin in cardiomyocytes. Am J Physiol Regul Integr Comp Physiol 280: R1399–R1406, 2001.Link | ISI | Google Scholar49 Takemoto F, Uchida S, Ogata E, and Kurokawa K. Endothelin-1 and endothelin-3 binding to rat nephrons. Am J Physiol Renal Fluid Electrolyte Physiol 264: F827–F832, 1993.Link | ISI | Google Scholar50 Taylor TA, Gariepy CE, Pollock DM, and Pollock JS. Unique endothelin receptor binding in kidneys of ETB receptor deficient rats. Am J Physiol Regul Integr Comp Physiol 284: R674–R681, 2003.Link | ISI | Google Scholar51 Ujiie K, Terada Y, Nonoguchi H, Shinohara M, Tomita K, and Marumo F. Messenger RNA expression and synthesis of endothelin-1 along rat nephron segments. J Clin Invest 90: 1043–1048, 1992.Crossref | PubMed | ISI | Google Scholar52 Villamor E, Ruijtenbeek K, Pulgar V, De Mey JG, and Blanco CE. Vascular reactivity in intrapulmonary arteries of chicken embryos during transition to ex ovo life. Am J Physiol Regul Integr Comp Physiol 282: R917–R927, 2002.Link | ISI | Google Scholar53 Wilkes BM, Susin M, Mento PF, Maciaca CM, Girardi EP, Boss E, and Nord EP. Localization of endothelin-like immunoreactivity in rat kidneys. Am J Physiol Renal Fluid Electrolyte Physiol 260: F913–F920, 1991.Link | ISI | Google Scholar54 Wilkins FC Jr, Alberola A, Mizelle HL, Opgenorth TJ, and Granger JP. Systemic hemodynamics and renal function during long-term pathophysiological increases in circulating endothelin. Am J Physiol Regul Integr Comp Physiol 268: R375–R381, 1995.Link | ISI | Google Scholar55 Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki K, Goto Y, and Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332: 411–415, 1988.Crossref | PubMed | ISI | Google Scholar56 Yip AW and Krukoff TL. Endothelin-A receptors and NO mediate decrease in arterial pressure during recovery from restraint. Am J Physiol Regul Integr Comp Physiol 282: R881–R889, 2002.Link | ISI | Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformationCited ByPathogenesis of HypertensionEffects of salt status and blockade of mineralocorticoid receptors on aldosterone-induced cardiac injury19 September 2013 | Hypertension Research, Vol. 37, No. 2Hypertension: Physiology and Pathophysiology1 October 2012Developmental changes in mesenteric artery reactivity in embryonic and newly hatched chicks28 May 2011 | Journal of Comparative Physiology B, Vol. 181, No. 8Adaptation to Nephron Loss and Mechanisms of Progression in Chronic Kidney DiseasePeroxisome Proliferator–Activated Receptors and The Metabolic Syndrome1 April 2009 | The Indonesian Biomedical Journal, Vol. 1, No. 1Teleost fish osmoregulation: what have we learned since August Krogh, Homer Smith, and Ancel KeysDavid H. Evans1 August 2008 | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 295, No. 2Low NaCl intake elevates renal medullary endothelin-1 and endothelin A (ET A ) receptor mRNA but not the sensitivity of renal Na + excretion to ET A receptor blockade in ratsActa Physiologica, Vol. 192, No. 3Role of the Kidney in HypertensionEndothelin, the kidney, and hypertensionCurrent Hypertension Reports, Vol. 8, No. 4Blood pressure regulation by ETA and ETB receptors in conscious, telemetry-instrumented mice and role of ETA in hypertension produced by selective ETB blockadeRyan M. Fryer, Pamela A. Rakestraw, Patricia N. Banfor, Bryan F. Cox, Terry J. Opgenorth, and Glenn A. Reinhart1 June 2006 | American Journal of Physiology-Heart and Circulatory Physiology, Vol. 290, No. 6Renal EndothelinPeroxisome Proliferator-Activated Receptor-α Activation Reduces Salt-Dependent Hypertension During Chronic Endothelin B Receptor BlockadeHypertension, Vol. 46, No. 2Physiological actions of renal collecting duct endothelinJeffrey L. Garvin, and Marcela Herrera1 May 2005 | American Journal of Physiology-Renal Physiology, Vol. 288, No. 5Role of endothelin in mediating postmenopausal hypertension in a rat modelLicy L. Yanes, Damian G. Romero, Valeria E. Cucchiarelli, Lourdes A. Fortepiani, Celso E. Gomez-Sanchez, Francisco Santacruz, and Jane F. Reckelhoff1 January 2005 | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 288, No. 1Arterial Pressure Response to the Antioxidant Tempol and ET B Receptor Blockade in Rats on a High-Salt DietHypertension, Vol. 44, No. 5Endothelin stimulates endothelial nitric oxide synthase expression in the thick ascending limbMarcela Herrera, and Jeffrey L. Garvin1 August 2004 | American Journal of Physiology-Renal Physiology, Vol. 287, No. 2 More from this issue > Volume 285Issue 2August 2003Pages R298-R301 Copyright & PermissionsCopyright © 2003 the American Physiological Societyhttps://doi.org/10.1152/ajpregu.00249.2003PubMed12855412History Published online 1 August 2003 Published in print 1 August 2003 Metrics
Referência(s)