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• W1995380245 abstract "HomeHypertensionVol. 61, No. 6Endothelin, Kidney Disease, and Hypertension Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBEndothelin, Kidney Disease, and Hypertension Joshua S. Speed and David M. Pollock Joshua S. SpeedJoshua S. Speed From the Department of Medicine, Georgia Regents University, Augusta, GA. Search for more papers by this author and David M. PollockDavid M. Pollock From the Department of Medicine, Georgia Regents University, Augusta, GA. Search for more papers by this author Originally published22 Apr 2013https://doi.org/10.1161/HYPERTENSIONAHA.113.00595Hypertension. 2013;61:1142–1145Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2013: Previous Version 1 IntroductionSince its discovery in 1988, endothelin-1 (ET-1) has been widely studied in a diverse number of fields, including neurology, cardiology, development, and to a greater extent, nephrology and hypertension.1,2 Through the activation of its 2 receptors, ETA and ETB, ET-1 influences blood pressure by numerous mechanisms, making it an attractive target for treatment of hypertension and other diseases.3–10 Although antagonists of the ET-1 system are highly effective in experimental models of hypertension and recently have been shown effective in resistant essential hypertension,7,11,12 their translation to the clinic has been disappointing thus far because of various side effects, including fluid retention/edema and liver toxicity.13,14 In fact, only 2 ET-1 receptor antagonists have been approved by the Food and Drug Administration for the use in humans, ambrisentan and bosentan, an ETA antagonist and dual ETA/ETB antagonist, respectively. The sole indication thus far approved is for the treatment of pulmonary hypertension.15 However, several receptor-specific antagonists are available and are going through animal testing and clinical trials. This review will focus on the recent progress of how ET-1 affects blood pressure and the future use of ET-1 receptor antagonists for the treatment of kidney disease and hypertension.14ET ReceptorsEither ETA or ETB or both receptors are located on almost every cell type throughout the body. ETA receptors are mostly located on vascular smooth muscle cells, and activation is not only normally prohypertensive through potent vasoconstriction but also have significant effects to increase inflammation, oxidative stress, and increases in proteinuria through direct changes on renal glomerular permeability.12,16,17 ETB receptors, however, function quite the opposite, being mostly antihypertensive. Vascular ETB receptors are mainly located on the endothelium, and activation leads to vasodilation through enhanced nitric oxide production.18 The highest concentration of ETB receptors are located on renal collecting duct cells and are important in long-term blood pressure regulation by directly inhibiting sodium uptake.18 Chronic disruption of the ETB receptor, either genetically or pharmacologically, results in salt-sensitive hypertension.18 Because the hypertensive actions of ETB receptor disruption can be abolished by ETA receptor antagonism, it is widely believed that ETB receptors protect against ETA receptor activation, and a balance between the 2 receptor subtypes is required for the maintenance of blood pressure. For greater details into the known mechanisms of ET receptor activation, especially within the kidney, the authors direct us to a recent review by Kohan et al.18Targeting ET in the KidneyDepending on which part of the kidney ET-1 is produced (cortex versus medulla), and which receptor is activated, renal ET-1 can have dramatically different effects on blood pressure. For instance, cortical ET-1 causes hypertension by increasing renal vascular resistance and reducing glomerular filtration rate. Furthermore, cortical ET-1 expression is upregulated in a number of hypertensive models.11,19,20 Even more specifically, glomerular ETA activation may lead to hypertension by increasing inflammation through enhanced production of monocyte chemoattractant protein-1 and other proinflammatory factors, such as cell adhesion molecules, thereby sequestering macrophages and lymphocytes.17 These immune cells, in turn, release a number of factors that act within to kidney to cause vasoconstriction and increases in sodium reabsorption, resulting in higher blood pressure. This has been proposed to play a role in the pathophysiology of numerous hypertensive states, including angiotensin II (AngII) hypertension and early life stress.21–24 Interestingly, ET-1 causes glomerular and vascular inflammation in the absence of hypertension, suggesting that ET-1 antagonists could have even greater beneficial outcomes beyond that of blood pressure reduction.17 Therefore, cortical ET-1 is prohypertensive by increasing renal vascular resistance, and directly promoting infiltration of inflammatory cells, specifically to the glomerulus.In contrast to the renal cortex, renal medullary ET-1 reduces blood pressure by directly inhibiting sodium reabsorption on the collecting duct and increasing medullary blood flow through activation of the ETB receptor. Inner medullary collecting ducts produce the most ET-1 within the kidney (≈10 times more than any other nephron segment). Known mediators of ET-1 effects on tubular and vasa recta function include increased production of nitric oxide and 20-HETE.18 Under normal circumstances, activation of this system is directly dependent on the level of salt intake.25 Moreover, at least half of the immunoreactive ET-1 found in urine is derived from the renal collecting duct.26 Blockade of ETB receptors, either genetically or pharmacologically, results in hypertension that is highly sensitive to salt intake.18,27 Impairment of this pronatriuretic pathway as evidenced by reductions in medullary ET-1 production in hypertension is observed in the Dahl salt-sensitive rat.27 These data suggest that alterations in medullary ETB receptor function could be an important mediator of salt-sensitive hypertension; however, until we understand the specific mechanisms that are responsible for regulating ETB receptor function, it will be difficult to discern how to overcome salt sensitivity attributed to this pathway.Sex Differences in ET-1 SignalingIt is well established that sex differences exist in the development of cardiovascular disease and hypertension, in that premenopausal women are less likely to develop hypertension compared with men.28–30 There is growing evidence that ET-1 may play a role in the differential regulation of blood pressure between men and women. Some of the more compelling data come from very intricate studies by Nakano and Pollock,31 where it was shown that direct infusion of an ETB agonist into the renal medulla increases urine flow rate and sodium excretion of male and female rats. Interestingly, the natriuretic response was only present in females when the endogenous ligand, ET-1, was infused. The lack of natriuresis in the males in response to ET-1 was attributed to an ETA-mediated reduction in medullary blood flow, thereby offsetting any ETB-mediated tubular effects. Furthermore, female rats also displayed a component of ETA-dependent natriuresis that was absent in males.31 Therefore, it seems there is an ETA-mediated protection against hypertension in female rats that does not exist in males.A number of laboratories have provided clear evidence that ET-1 plays a role in AngII salt-induced hypertension because ETA or combined ETA/ETB antagonists can block the hypertensive effects of chronic AngII infusion.32 It is known that female rats are not as susceptible to AngII hypertension, and so it has become increasingly evident that ET-1 may be important in the protection against salt-induced hypertension afforded to female rats.33 For instance, renal medullary ETB receptor function is completely lost in AngII hypertensive male rats, whereas still intact in females. This reduced ETB function is associated with a reduction in ETB ligand binding in male rats, but not in female rats.6 Furthermore, blockade of ETB receptors increases blood pressure to a more significant extent in female AngII hypertensive rats compared with males (unpublished data). Taken together, these data suggest that AngII, either directly or indirectly, reduces ETB receptor function in male rats; however, ETB receptor function in female rats is preserved in AngII hypertension, providing a potential mechanism of protection against high blood pressure.ET in Chronic Kidney DiseaseSeveral lines of evidence suggest that ET-1 is a major factor in the development of chronic kidney disease, and more specifically, contributes to hypertension, proteinuria, and renal inflammation in chronic kidney disease. In fact, ET-1 directly stimulates inflammation both in the vasculature and in the kidney, and this occurs in the absence of hypertension.7,17,34 Recently, it was shown that an ETA receptor-specific antagonist reduces blood pressure and proteinuria in patients with chronic kidney disease.34 These reductions were in addition to the normal treatments already being administered, including angiotensin receptor blockers and converting enzyme inhibitors. Therefore, although the initial insult in the development of chronic kidney disease may be multifactorial and complex, ET-1 seems to play an important role in the development and progression of the disease. Thus, treatment with ETA receptor antagonists may prove to be beneficial in cases where standard treatments are not sufficient, especially when blood pressure reduction is needed.More recent data suggest that selective ETA antagonism improves outcomes in diabetic nephropathy. The ASCEND (A Study of Cardiovascular Events iN Diabetes) study shows significant reductions in proteinuria among patients with diabetic nephropathy given the ETA antagonist, avosentan; however, this study was cut short because of fluid retention among the treatment group. Although this was disappointing, it must be pointed out that the doses used in this trial were very high relative to the known dose–response effect on fluid retention observed in prior phase 2 trials and the lack of a dose–response effect on proteinuria.35 In fact, a much lower dose of atrasentan, another selective ETA antagonist, reduces albuminuria, but with far less peripheral edema than the ASCEND trial.18 These studies highlight not only the importance of the ETA receptor in mediating kidney disease in diabetes mellitus but also the great potential that these drugs may have in treating renal disease associated with glomerular injury and proteinuria.ET in the Pathogenesis of PreeclampsiaPreeclampsia is a disease of pregnancy in which the mother becomes hypertensive in the third trimester of gestation. It is thought to be caused by abnormal remodeling of uterine spiral arteries, leading to placental insufficiency and the release of factors, such as soluble fms-like tyrosine kinase-1 and tumor necrosis factor-α, from the placenta into the blood stream that result in overproduction of ET-1 by the vascular endothelium and the renal cortex.11,36–39 In fact, a very well-established model of preeclampsia in the rat, in which clamps are placed on the ovarian arteries and the descending aorta to reduce blood flow to the placenta, is characterized by hypertension that is abolished by ETA receptor antagonism.37,40 Furthermore, soluble fms-like tyrosine kinase-1 and tumor necrosis factor-α infusion into pregnant rats result in hypertension that is also mediated by ETA receptor activation.19,20 Although ETA receptor antagonists seem promising for the treatment of pregnancy-induced hypertension, there is the potential problem of teratogenicity. ETA receptor knockout mice have severe developmental defects that are lethal and so it is unlikely that any pharmaceutical company would want to or be able to test this idea.18 Whether drugs can be developed that do not cross the placenta is not well established.What is the Future of ET-1 Antagonists for the Treatment of Hypertension?Although it is well established that ET-1 plays an important role in blood pressure control and alterations in this system can lead to hypertensive consequences, there are still no approved ET-1 antagonists for the treatment of arterial hypertension. Several fairly large clinical trials demonstrated that both ETA selective and combined ETA and ETB antagonists reduce blood pressure in patients with resistant essential hypertension.13,41 However, further development of these drugs for use in resistant hypertension has been thwarted for several potential reasons that are not all scientific. The ETA antagonist, darusentan, produced a significant reduction in 24-hour blood pressure in hypertension subjects already being treated with at least 3 other antihypertensive medications, yet for reasons unclear, the primary end point of clinic blood pressure was not significantly different from placebo on the final day of the trial. This led to the decision of the company developing the compound, Gilead, to discontinue further development. This decision was particularly disappointing also because of the additional benefits observed in hypertensive patients, including reduced glycemia, improved lipid metabolism, and reductions in proteinuria.13,41As previously mentioned, another important factor that seems to have contributed to reduced enthusiasm for developing ET blockers for the treatment of hypertension is edema. Fluid retention is a serious side effect that has been observed with all the various antagonists, but this was a particularly significant problem in patients with diabetic nephropathy in the ASCEND trial that was terminated early.35 However, lower doses that maintain efficacy have fewer issues with fluid retention and seem to be manageable by adjusting cotreatment with diuretics.18The delicate balance between the ETA and ETB receptors is required for the normal regulation of fluid and water balance (Figure). For instance, as sodium intake is increased, the ETB receptor becomes increasingly more important in blood pressure control because of its role in reducing renal tubular sodium reabsorption.18 Although disruption of the balance between receptor subtype activity may ultimately lead to hypertension, that is, loss of ETB and gain of ETA receptor activity, knowledge of the distinct function of these receptors is needed when attempting to treat different forms of hypertension. Furthermore, there are a number of factors that shift balance between ETA and ETB receptors, including salt intake,12,42–46 sex,6,31,47 and AngII, and may contribute to the somewhat confusing results from clinical trials compared with the very clear findings in experimental models.Finally, one cannot ignore the business aspects of developing new drug therapies. New drugs that may require careful management and cotherapies in the early treatment phase may be difficult to manage when dealing with a chronic disease that is not immediately life-threatening. Both patient and physician compliance can be difficult when focusing on what can be viewed as simple blood pressure management. However, patients with resistant hypertension are on many different medications without blood pressure control and so the effort should be worthwhile. In addition, it is important to note that most of the ET antagonists are nearing the end of their initial patent life. Although a limited degree of exclusivity may be allowable, the earning potential may not be worth the costly investment required for clinical trials. The mistakes of the previous clinical trials are also an obstacle to overcome from a perceptual basis. Companies are reluctant to invest in drugs that have been tainted by a failed trial even when there are rational scientific explanations. Nonetheless, when one studies the history and considers the scientific specifics, there remains the valid possibility that the ET antagonists are potentially useful, life-prolonging drugs in patients experiencing hypertension.Download figureDownload PowerPointFigure. General schematic showing major actions of endothelin-1 (ET-1) along the nephron. AngII indicates angiotensin II; GFR, glomerular filtration rate; GLOM, glomerulus; GP, glomerular permeability; IMCD, inner medullary collecting duct; MCP-1, monocyte chemoattractant protein-1; NKCC, sodium, potassium, 2-chloride cotransporter; and TAL, thick ascending limb of the loop of Henle.DisclosuresDr Speed was the recipient of a Post-doctoral Fellowship Award from the American Heart Association during the course of preparing the article. Dr Pollock was supported by National Institutes of Health grants, HL69999 and HL095499, as well as a grant from the Cardiovascular Discovery Institute at Georgia Regents University.FootnotesCorrespondence to David M. Pollock, Department of Medicine, Georgia Regents University, Section of Experimental Medicine, CB2200, 1459 Laney Walker Blvd, Augusta, GA 30912. E-mail [email protected]References1. Capone C, Faraco G, Coleman C, Young CN, Pickel VM, Anrather J, Davisson RL, Iadecola C. Endothelin 1-dependent neurovascular dysfunction in chronic intermittent hypoxia.Hypertension. 2012; 60:106–113.LinkGoogle Scholar2. Bruno RM, Sudano I, Ghiadoni L, Masi L, Taddei S. Interactions between sympathetic nervous system and endogenous endothelin in patients with essential hypertension.Hypertension. 2011; 57:79–84.LinkGoogle Scholar3. Kappers MH, de Beer VJ, Zhou Z, Danser AH, Sleijfer S, Duncker DJ, van den Meiracker AH, Merkus D. Sunitinib-induced systemic vasoconstriction in swine is endothelin mediated and does not involve nitric oxide or oxidative stress.Hypertension. 2012; 59:151–157.LinkGoogle Scholar4. Kappers MtHW, Smedts FMM, Horn T, van Esch JHM, Sleijfer S, Leijten F, Wesseling S, Strevens H, Jan Danser AH, van den Meiracker AH. The vascular endothelial growth factor receptor inhibitor sunitinib causes a preeclampsia-like syndrome with activation of the endothelin system.Hypertension. 2011; 58: 295–302.LinkGoogle Scholar5. Meens MJ, Mattheij NJ, Nelissen J, Lemkens P, Compeer MG, Janssen BJ, De Mey JG. Calcitonin gene-related peptide terminates long-lasting vasopressor responses to endothelin 1 in vivo.Hypertension. 2011; 58:99–106.LinkGoogle Scholar6. Kittikulsuth W, Pollock JS, Pollock DM. Sex differences in renal medullary endothelin receptor function in angiotensin II hypertensive rats.Hypertension. 2011; 58:212–218.LinkGoogle Scholar7. Dhaun N, MacIntyre IM, Kerr D, Melville V, Johnston NR, Haughie S, Goddard J, Webb DJ. Selective endothelin-A receptor antagonism reduces proteinuria, blood pressure, and arterial stiffness in chronic proteinuric kidney disease.Hypertension. 2011; 57:772–779.LinkGoogle Scholar8. Dhaun N, Webb DJ. Dual endothelin-converting enzyme/neutral endopeptidase inhibition.Hypertension. 2011; 57: 667–669.LinkGoogle Scholar9. LaMarca B, Parrish M, Ray LF, Murphy SR, Roberts L, Glover P, Wallukat G, Wenzel K, Cockrell K, Martin JN, Ryan MJ, Dechend R. Hypertension in response to autoantibodies to the angiotensin II type I receptor (AT1-AA) in pregnant rats: role of endothelin-1.Hypertension. 2009; 54:905–909.LinkGoogle Scholar10. Kisanuki YY, Emoto N, Ohuchi T, Widyantoro B, Yagi K, Nakayama K, Kedzierski RM, Hammer RE, Yanagisawa H, Williams SC, Richardson JA, Suzuki T, Yanagisawa M. Low blood pressure in endothelial cell-specific endothelin 1 knockout mice.Hypertension. 2010; 56:121–128.LinkGoogle Scholar11. George EM, Granger JP. Linking placental ischemia and hypertension in preeclampsia.Hypertension. 2012; 60: 507–511.LinkGoogle Scholar12. Chen DD, Dong YG, Yuan H, Chen AF. Endothelin 1 activation of endothelin A receptor/NADPH oxidase pathway and diminished antioxidants critically contribute to endothelial progenitor cell reduction and dysfunction in salt-sensitive hypertension.Hypertension. 2012; 59:1037–1043.LinkGoogle Scholar13. Bakris GL, Lindholm LH, Black HR, Krum H, Linas S, Linseman JV, Arterburn S, Sager P, Weber M. Divergent results using clinic and ambulatory blood pressures.Hypertension. 2010; 56: 824–830.LinkGoogle Scholar14. Raichlin E, Prasad A, Mathew V, Kent B, Holmes DR, Pumper GM, Nelson RE, Lerman LO, Lerman A. Efficacy and safety of atrasentan in patients with cardiovascular risk and early atherosclerosis.Hypertension. 2008; 52:522–528.LinkGoogle Scholar15. Liang F, Yang S, Yao L, Belardinelli L, Shryock J. Ambrisentan and tadalafil synergistically relax endothelin-induced contraction of rat pulmonary arteries.Hypertension. 2012; 59:705–711.LinkGoogle Scholar16. Elmarakby AA, Loomis ED, Pollock JS, Pollock DM. NADPH oxidase inhibition attenuates oxidative stress but not hypertension produced by chronic ET-1.Hypertension. 2005; 45:283–287.LinkGoogle Scholar17. Saleh MA, Boesen EI, Pollock JS, Savin VJ, Pollock DM. Endothelin-1 increases glomerular permeability and inflammation independent of blood pressure in the rat.Hypertension. 2010; 56:942–949.LinkGoogle Scholar18. Kohan DE, Rossi NF, Inscho EW, Pollock DM. Regulation of blood pressure and salt homeostasis by endothelin.Physiol Rev. 2011; 91:1–77.CrossrefMedlineGoogle Scholar19. Murphy SR, LaMarca BB, Cockrell K, Granger JP. Role of endothelin in mediating soluble fms-like tyrosine kinase 1-induced hypertension in pregnant rats.Hypertension. 2010; 55:394–398.LinkGoogle Scholar20. LaMarca B, Speed J, Fournier L, Babcock SA, Berry H, Cockrell K, Granger JP. Hypertension in response to chronic reductions in uterine perfusion in pregnant rats: effect of tumor necrosis factor-alpha blockade.Hypertension. 2008; 52:1161–1167.LinkGoogle Scholar21. Loria AS, Pollock DM, Pollock JS. Early life stress sensitizes rats to angiotensin II-induced hypertension and vascular inflammation in adult life.Hypertension. 2010; 55:494–499.LinkGoogle Scholar22. Lob HE, Marvar PJ, Guzik TJ, Sharma S, McCann LA, Weyand C, Gordon FJ, Harrison DG. Induction of hypertension and peripheral inflammation by reduction of extracellular superoxide dismutase in the central nervous system.Hypertension. 2010; 55:277–83, 6p following 283.LinkGoogle Scholar23. Harrison DG, Guzik TJ, Lob HE, Madhur MS, Marvar PJ, Thabet SR, Vinh A, Weyand CM. Inflammation, immunity, and hypertension.Hypertension. 2011; 57:132–140.LinkGoogle Scholar24. Kennedy DJ, Chen Y, Huang W, Viterna J, Liu J, Westfall K, Tian J, Bartlett DJ, Tang WH, Xie Z, Shapiro JI, Silverstein RL. CD36 and Na/K-ATPase-α1 form a proinflammatory signaling loop in kidney.Hypertension. 2013; 61:216–224.LinkGoogle Scholar25. Speed JS, George EM, Arany M, Cockrell K, Granger JP. Role of 20-hydroxyeicosatetraenoic acid in mediating hypertension in response to chronic renal medullary endothelin type B receptor blockade.PLoS One. 2011; 6:e26063.CrossrefMedlineGoogle Scholar26. 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. 2004; 114:504–511.CrossrefMedlineGoogle Scholar27. Speed JS, LaMarca B, Berry H, Cockrell K, George EM, Granger JP. Renal medullary endothelin-1 is decreased in Dahl salt-sensitive rats.Am J Physiol Regul Integr Comp Physiol. 2011; 301:R519–R523.CrossrefMedlineGoogle Scholar28. Sullivan JC, Bhatia K, Yamamoto T, Elmarakby AA. Angiotensin (1-7) receptor antagonism equalizes angiotensin II-induced hypertension in male and female spontaneously hypertensive rats.Hypertension. 2010; 56:658–666.LinkGoogle Scholar29. Ojeda NB, Hennington BS, Williamson DT, Hill ML, Betson NE, Sartori-Valinotti JC, Reckelhoff JF, Royals TP, Alexander BT. Oxidative stress contributes to sex differences in blood pressure in adult growth-restricted offspring.Hypertension. 2012; 60:114–122.LinkGoogle Scholar30. Sartori-Valinotti JC, Iliescu R, Yanes LL, Dorsett-Martin W, Reckelhoff JF. Sex differences in the pressor response to angiotensin II when the endogenous renin-angiotensin system is blocked.Hypertension. 2008; 51:1170–1176.LinkGoogle Scholar31. Nakano D, Pollock DM. Contribution of endothelin A receptors in endothelin 1-dependent natriuresis in female rats.Hypertension. 2009; 53:324–330.LinkGoogle Scholar32. Sasser JM, Pollock JS, Pollock DM. Renal endothelin in chronic angiotensin II hypertension.Am J Physiol Regul Integr Comp Physiol. 2002; 283:R243–R248.CrossrefMedlineGoogle Scholar33. Reckelhoff JF, Zhang H, Srivastava K. Gender differences in development of hypertension in spontaneously hypertensive rats: role of the renin-angiotensin system.Hypertension. 2000; 35(1 Pt 2):480–483.LinkGoogle Scholar34. Dhaun N, Johnston NR, Goddard J, Webb DJ. Chronic selective endothelin A receptor antagonism reduces serum uric acid in hypertensive chronic kidney disease.Hypertension. 2011; 58:e11–e12.LinkGoogle Scholar35. Mann JF, Green D, Jamerson K, Ruilope LM, Kuranoff SJ, Littke T, Viberti G; ASCEND Study Group. Avosentan for overt diabetic nephropathy.J Am Soc Nephrol. 2010; 21:527–535.CrossrefMedlineGoogle Scholar36. LaMarca BD, Gilbert J, Granger JP. Recent progress toward the understanding of the pathophysiology of hypertension during preeclampsia.Hypertension. 2008; 51:982–988.LinkGoogle Scholar37. Roberts L, LaMarca BB, Fournier L, Bain J, Cockrell K, Granger JP. Enhanced endothelin synthesis by endothelial cells exposed to sera from pregnant rats with decreased uterine perfusion.Hypertension. 2006; 47:615–618.LinkGoogle Scholar38. Gilbert JS, Ryan MJ, LaMarca BB, Sedeek M, Murphy SR, Granger JP. Pathophysiology of hypertension during preeclampsia: linking placental ischemia with endothelial dysfunction.Am J Physiol Heart Circ Physiol. 2008; 294:H541–H550.CrossrefMedlineGoogle Scholar39. Abdalvand A, Morton JS, Bourque SL, Quon AL, Davidge ST. Matrix metalloproteinase enhances big-endothelin-1 constriction in mesenteric vessels of pregnant rats with reduced uterine blood flow.Hypertension. 2013; 61:488–493.LinkGoogle Scholar40. Tam Tam KB, George E, Cockrell K, Arany M, Speed J, Martin JN, Lamarca B, Granger JP. Endothelin type A receptor antagonist attenuates placental ischemia-induced hypertension and uterine vascular resistance.Am J Obstet Gynecol. 2011; 204:330.e1–330.e4.CrossrefGoogle Scholar41. 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. 2009; 374:1423–1431.CrossrefMedlineGoogle Scholar42. Kassab S, Miller MT, Novak J, Reckelhoff J, Clower B, Granger JP. Endothelin-A receptor antagonism attenuates the hypertension and renal injury in Dahl salt-sensitive rats.Hypertension. 1998; 31(1 Pt 2):397–402.CrossrefMedlineGoogle Scholar43. D’Angelo G, Loria AS, Pollock DM, Pollock JS. Endothelin activation of reactive oxygen species mediates stress-induced pressor response in Dahl salt-sensitive prehypertensive rats.Hypertension. 2010; 56:282–289.LinkGoogle Scholar44. Williams JM, Zhao X, Wang MH, Imig JD, Pollock DM. Peroxisome proliferator-activated receptor-alpha activation reduces salt-dependent hypertension during chronic endothelin B receptor blockade.Hypertension. 2005; 46:366–371.LinkGoogle Scholar45. Smith WE, Kane AV, Campbell ST, Acheson DW, Cochran BH, Thorpe CM. Shiga toxin 1 triggers a ribotoxic stress response leading to p38 and JNK activation and induction of apoptosis in intestinal epithelial cells.Infect Immun. 2003; 71:1497–1504.CrossrefMedlineGoogle Scholar46. Lima VV, Giachini FR, Carneiro FS, Carneiro ZN, Saleh MA, Pollock DM, Fortes ZB, Carvalho MH, Ergul A, Webb RC, Tostes RC. O-GlcNAcylation contributes to augmented vascular reactivity induced by endothelin 1.Hypertension. 2010; 55:180–188.LinkGoogle Scholar47. 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. 2003; 41(3 Pt 2):657–662.LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Lu R and Zheng X (2021) Plasma Levels of Big Endothelin-1 Are Associated with Renal Insufficiency and In-Hospital Mortality of Immune Thrombotic Thrombocytopenic Purpura, Thrombosis and Haemostasis, 10.1055/a-1508-8347, 122:03, (344-352), Online publication date: 1-Mar-2022. Hashemi S, Arab H, Seifi B and Muhammadnejad S (2021) A comparison effects of l-citrulline and l-arginine against cyclosporine-induced blood pressure and biochemical changes in the rats, Hipertensión y Riesgo Vascular, 10.1016/j.hipert.2021.08.002, 38:4, (170-177), Online publication date: 1-Oct-2021. Shabaka A, Cases-Corona C and Fernandez-Juarez G (2021) Therapeutic Insights in Chronic Kidney Disease Progression, Frontiers in Medicine, 10.3389/fmed.2021.645187, 8 Yang Y, Li M, Zou X, Chen C, Zheng S, Fu C, Chen K, Jose P, Lan C and Liu Y (2020) Role of GRK4 in the regulation of the renal ETB receptor in hypertension, The FASEB Journal, 10.1096/fj.201902552R, 34:9, (11594-11604), Online publication date: 1-Sep-2020. Eroglu E, Kocyigit I and Lindholm B (2020) The endothelin system as target for therapeutic interventions in cardiovascular and renal disease, Clinica Chimica Acta, 10.1016/j.cca.2020.03.008, 506, (92-106), Online publication date: 1-Jul-2020. Douma L, Solocinski K, Masten S, Barral D, Barilovits S, Jeffers L, Alder K, Patel R, Wingo C, Brown K, Cain B and Gumz M (2020) EDN1-AS, A Novel Long Non-coding RNA Regulating Endothelin-1 in Human Proximal Tubule Cells, Frontiers in Physiology, 10.3389/fphys.2020.00209, 11 Törmänen S, Lakkisto P, Eräranta A, Kööbi P, Tikkanen I, N" @default.
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• W1995380245 cites W1997169304 @default.
• W1995380245 cites W2015170224 @default.
• W1995380245 cites W2041376120 @default.
• W1995380245 cites W2049862929 @default.
• W1995380245 cites W2049957217 @default.
• W1995380245 cites W2063891422 @default.
• W1995380245 cites W2078144805 @default.
• W1995380245 cites W2085323089 @default.
• W1995380245 cites W2087696592 @default.
• W1995380245 cites W2098228565 @default.
• W1995380245 cites W2101580559 @default.
• W1995380245 cites W2102504529 @default.
• W1995380245 cites W2105289127 @default.
• W1995380245 cites W2105614662 @default.
• W1995380245 cites W2105901029 @default.
• W1995380245 cites W2110051876 @default.
• W1995380245 cites W2110359510 @default.
• W1995380245 cites W2112021227 @default.
• W1995380245 cites W2113257066 @default.
• W1995380245 cites W2115841084 @default.
• W1995380245 cites W2117185007 @default.
• W1995380245 cites W2117288014 @default.
• W1995380245 cites W2117603700 @default.
• W1995380245 cites W2121079663 @default.
• W1995380245 cites W2122033270 @default.
• W1995380245 cites W2123969526 @default.
• W1995380245 cites W2129815519 @default.
• W1995380245 cites W2132961242 @default.
• W1995380245 cites W2136003807 @default.
• W1995380245 cites W2136290315 @default.
• W1995380245 cites W2137701513 @default.
• W1995380245 cites W2137839491 @default.
• W1995380245 cites W2141528467 @default.
• W1995380245 cites W2143516414 @default.
• W1995380245 cites W2146371213 @default.
• W1995380245 cites W2149747723 @default.
• W1995380245 cites W2150722617 @default.
• W1995380245 cites W2153055557 @default.
• W1995380245 cites W2153891411 @default.
• W1995380245 cites W2156753852 @default.
• W1995380245 cites W2156835401 @default.
• W1995380245 cites W2158050604 @default.
• W1995380245 cites W2160382960 @default.
• W1995380245 cites W2161040394 @default.
• W1995380245 cites W2161358815 @default.
• W1995380245 cites W2162946013 @default.
• W1995380245 cites W4297361592 @default.
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