Pathophysiological Roles of Endothelin Receptors in Cardiovascular Diseases

Abstract

Abstract. Endothelin (ET)-1 derived from endothelial cells has a much more important role in cardiovascular system regulation than the ET-2 and ET-3 isoforms. Numerous lines of evidence indicate that ET-1 possesses a number of biological activities leading to cardiovascular diseases (CVD) including hypertension and atherosclerosis. Physiological and pathophysiological responses to ET-1 in various tissues are mediated by interactions with ET A -and ET B -receptor subtypes. Both subtypes on vascular smooth muscle cells mediate vasoconstriction, whereas the ET B -receptor subtype on endothelial cells contributes to vasodilatation and ET-1 clearance. Although selective ET A -or nonselective ET A /ET B -receptor antagonisms have been assumed as potential strategies for the treatment of several CVD based on clinical and animal experiments, it remains unclear which antagonisms are suitable for individuals with CVD because upregulation of the nitric oxide system via the ET B receptor is responsible for vasoprotective effects such as vasodilatation and anti-cell proliferation. In this review, we have summarized the current understanding regarding the role of ET receptors, especially the ET B receptor, in CVD.

High glucose-induced increased expression of endothelin-1 in human endothelial cells is mediated by activated CCAAT/enhancer-binding proteins

“…[5] The endothelin system comprises biological active peptides called endothelins, endothelin converting enzymes, and specific cellular receptors. [6][7][8] Endothelins regulate important physiological processes including vascular tonus [9], cellular growth and proliferation. [10] However, in pathological conditions such as diabetes mellitus, dysregulation of the endothelin system, characterized by enhanced expression, activity or responsiveness of different constituents contributes to dysfunction of the vascular cells.…”

A novel peptide of endothelin family, 31 amino-acid length endothelin in patients with acute myocardial infarction

“…More recently, ET-1 receptor blockers, which also block ET-1(1-31) effects (23)(24)(25), became available in clinical medicine including pulmonary hypertension and myocardial infarction (41). The use of these drugs to inhibit ET-1(1-31) after myocardial infarction will help understanding of mechanism of ET-1(1-31) by future studies.…”

Are Sildenafil Derivatives Useful Even in Unborn Males?

“…(4) is the increased sensitivity to big-ET-1 a direct result of fetomaternal impairment of NO production? and finally, (5) why are the vasoconstrictor responses to big-ET-1 less physiologically repressed by endogenous NO than those afforded by ET-1 in vessels of aging IUGR male rats?…”

“…Current wisdom suggests that big-ET-1 must be converted to ET-1, which subsequently activates endothelial and vascular smooth muscle cell ET B , as well as vascular ET A receptors. 5 Thus, in conditions in which endogenous NO production is altered, such as in IUGR male rats, 6 one would expect similarly enhanced vascular responsiveness to ET-1 and big-ET-1; this is not the case in the current article by Bourque et al 3 To further clarify this aspect, performing the same type of experiments in endotheliumdenuded arteries (with or without L-N G -nitroarginine methyl ester [L-NAME]) may be warranted.…”