Endothelin Receptor Blockers in Cardiovascular Disease

Rich, Stuart; McLaughlin, Vallerie V.

doi:10.1161/01.cir.0000094397.19932.78

Cited by 202 publications

(139 citation statements)

References 77 publications

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“…A conceivable usefulness of ET-receptor antagonists in the treatment of hypertension (64,71), chronic or acute heart failure (77) has not been established and currently does not seem to be promising.…”

Section: Discussionmentioning

confidence: 99%

Ambrisentan, a Non‐peptide Endothelin Receptor Antagonist

Vatter

Seifert

2006

Cardiovascular Drug Reviews

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Increasing numbers of experimental investigations and recently also of clinical trials strongly suggest an integral involvement of the endothelin (ET)-system in the pathophysiology of a variety of disease states, mainly of the cardiovascular system. Ambrisentan (LU 208075), a selective ET A -receptor antagonist, is an orally active diphenyl propionic acid derivative. It has been shown to have a very promising efficacy to safety ratio in the initial clinical trials. Phase II and Phase III trials with ambrisentan in pulmonary arterial hypertension have been performed. The pharmacological properties and data from the experimental investigations suggest additional possible uses of ambrisentan in the prevention of reperfusion injury after organ transplantation and in restenosis following coronary artery dilatation. Furthermore, the pharmacological profile of ambrisentan indicates that this drug may also be suitable in the treatment of cerebrovascular disorders. In the present article basic investigations, animal studies and clinical trials with ambrisentan are reviewed. This review may help to define pathophysiological conditions, in which ambrisentan could be indicated and further evaluated in appropriate preclinical and clinical trials.

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Section: Discussionmentioning

confidence: 99%

Ambrisentan, a Non‐peptide Endothelin Receptor Antagonist

Vatter

Seifert

2006

Cardiovascular Drug Reviews

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“…Moreover, our data suggest that the renal medullary ET B receptors may be a potential target for treatment of hypertension. Thus far, clinical studies utilizing ET-1 receptor blockers have shown little effect on blood pressure in hypertensive patients (22); however, the early ET-1 receptor blockers used were either combined ET A / ET B blockers or were ET A blockers, which lacked in vivo specificity (4). Because of the natriuretic and antihypertensive properties of ET B receptors, blockade of ET B receptors in these studies may have counteracted any beneficial effects of ET A receptor blockade.…”

Section: Perspectives and Significancementioning

confidence: 99%

Renal medullary endothelin-1 is decreased in Dahl salt-sensitive rats

Speed

LaMarca

Berry

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Although it is well established that the renal endothelin (ET-1) system plays an important role in regulating sodium excretion and blood pressure through activation of renal medullary ETB receptors, the role of this system in Dahl salt-sensitive (DS) hypertension is unclear. The purpose of this study was to determine whether the DS rat has abnormalities in the renal medullary endothelin system when maintained on a high sodium intake. The data indicate that Dahl saltresistant rats (DR) on a high-salt diet had a six-fold higher urinary endothelin excretion than in the DR rats with low Na ϩ intake (17.8 Ϯ 4 pg/day vs. 112 Ϯ 44 pg/day). In sharp contrast, urinary endothelin levels increased only twofold in DS rats in response to a high Na ϩ intake (13 Ϯ 2 pg/day vs. 29.8 Ϯ 5.5 pg/day). Medullary endothelin concentration in DS rats on a high-Na ϩ diet was also significantly lower than DR rats on a high-Na ϩ diet (31 Ϯ 2.8 pg/mg vs. 70.9 Ϯ 5 pg/mg). Furthermore, DS rats had a significant reduction in medullary ET B receptor expression compared with DR rats while on a high-Na ϩ diet. Finally, chronic infusion of ET-1 directly into the renal medulla blunted Dahl salt-sensitive hypertension. These data indicate that a decrease in medullary production of ET-1 in the DS rat could play an important role in the development of salt-sensitive hypertension observed in the DS rat.kidney; blood pressure; hypertension ENDOTHELIN-1 (ET-1) WAS FIRST characterized in 1988 as a potent vasoconstrictor released by endothelial cells (26). Two receptor subtypes have been since identified, ET A and ET B (24). Both of these receptors are located in the kidney with the highest concentration of ET B receptors existing within the medulla (11). Although the role of ET A receptors has been well characterized in the pathophysiology of experimental hypertension, the physiological importance of ET B receptors in modulating sodium excretion and blood pressure regulation in salt-sensitive hypertension is unclear. ET B activation inhibits sodium transport (15,18,19), and growing evidence suggests a critical role for the renal medullary endothelin system in the integrated response to a high-salt diet (6, 20 -21). For example, Pollock and others (4)have shown that renal ET-1 production is enhanced in response to 1 wk of a high-sodium diet, and intramedullary blockade of ET B receptors for 7 days leads to salt-sensitive hypertension. In addition, specific knockout of the ET B receptor gene and the ET-1 gene in the medullary collecting duct produces salt-sensitive hypertension (1, 6).Although there is growing evidence from a number of laboratories that the renal endothelin system via ET B receptor activation plays an important role in modulating renal pressure natriuresis and blood pressure regulation, very little is known about potential abnormalities in renal endothelin system in models of salt-sensitive hypertension. Our laboratory and others have reported that there is a rightward shift in the pressure natriuresis relationship in Dahl salt-sensitive r...

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“…Endothelin-1 is a vascular regulator that is produced by endothelial cells and cardiomyocytes, which has vasoconstrictive and mitotic effects via the stimulation of growth factors. It is also important in hypertension, acting as a blood pressure elevator (13,14). CD68, which belongs to the LAMP (lysosomal-associated membrane protein) family of glycoproteins, is expressed by monocytes and macrophages.…”

Section: Introductionmentioning

confidence: 99%

Increased Expression of E-cadherin, Endothelin-1, and CD68 in Preeclamptic Placentas

İrtegün¹,

Tekin²,

Alpayci³

2016

Erciyes Med J

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Objective: Preeclampsia (PE) is a complex pregnancy-specific disorder characterized by the onset of hypertension and proteinuria in the second trimester of pregnancy. The pathogenesis of PE still remains unknown. Revealing the specific proteins involved in placental functions is important for a better understanding of the pathogenesis of PE. In this study, we aimed to investigate the expression levels of E-cadherin, endothelin-1, and CD68 in both preeclamptic and normal placentas. Materials and Methods:In this study, placentas after birth at 35-38 weeks were included. Ten preeclamptic placentas and 10 normal placentas were used. The expression levels of E-cadherin, endothelin-1, and CD68 were measured by western blot.Results: It was observed that the expression of E-cadherin and endothelin-1 was not at detectable levels in normal placentas; however, E-cadherin and endothelin-1 were observed to be highly expressed in preeclamptic placentas. In addition, the expression of CD68 was found to be markedly increased in preeclamptic placentas in comparison to control placentas. Conclusion:The increased expression of E-cadherin, endothelin-1, and CD68 may play an important role in impaired trophoblast invasion, endothelial dysfunction, and inadequate spiral remodeling, which are key factors involved in the pathogenesis of PE.

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Endothelin Receptor Blockers in Cardiovascular Disease

Cited by 202 publications

References 77 publications

Ambrisentan, a Non‐peptide Endothelin Receptor Antagonist

Ambrisentan, a Non‐peptide Endothelin Receptor Antagonist

Renal medullary endothelin-1 is decreased in Dahl salt-sensitive rats

Increased Expression of E-cadherin, Endothelin-1, and CD68 in Preeclamptic Placentas

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