Endothelin and endothelin receptors in the renal and cardiovascular systems

Abstract

Endothelin-1 (ET-1) is a multifunctional hormone which regulates the physiology of the cardiovascular and renal systems. ET-1 modulates cardiac contractility, systemic and renal vascular resistance, salt and water renal reabsorption, and glomerular function. ET-1 is responsible for a variety of cellular events: contraction, proliferation, apoptosis, etc. These effects take place after the activation of the two endothelin receptors ET(A) and ET(B), which are present - among others - on cardiomyocytes, fibroblasts, smooth muscle and endothelial cells, glomerular and tubular cells of the kidney. The complex and numerous intracellular pathways, which can be contradictory in term of functional response depending on the receptor type, cell type and physiological situation, are described in this review. Many diseases share an enhanced ET-1 expression as part of the pathophysiology. However, the use of endothelin blockers is currently restricted to pulmonary arterial hypertension, and more recently to digital ulcer. The complexity of the endothelin system does not facilitate the translation of the molecular knowledge to clinical applications. Endothelin antagonists can prevent disease development but secondary undesirable effects limit their usage. Nevertheless, the increasing understanding of the effects of ET-1 on the cardiac and renal physiology maintains the endothelin system as a promising therapeutic target.

Targeting of Endothelin Receptors in the Healthy and Infarcted Rat Heart Using the PET Tracer18F-FBzBMS

“…This discrepancy is best explained by the absence of viable myocytes in the infarct region. Myocytes express ET-A at a basic level (3,24) and constitute most of the imaging signal in the remote and healthy myocardium. In the infarct region, however, myocytes are mostly absent, FIGURE 3.…”

“…Our preliminary results should be seen as a stimulus to implement molecular imaging in such studies. Heart-specific ET-A knockout mice have been developed recently (24,25) and may offer a good model for further detailed assessment of 18 F-FBzBMS and its usefulness to study disease mechanisms. In those animals, in which only cardiomyocytes are deficient of ET-A, further insights into the endothelial cellspecific signal in the infarct area may be obtained, but such work clearly exceeds the frame of our present study.…”

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

“…[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. [11,12] Hyperglycemia-induced vascular deleterious effects are partially mediated by the endothelin-1 (ET-1).…”

Roles of EDNs in regulating oviductal NO synthesis and smooth muscle motility in cows

“…Reproduction (2016) 151 615-622 (Pollock et al 1995, Vignon-Zellweger et al 2012. As EDNRA has a low affinity for EDN3 (Yanagisawa 1994), only EDN1 and EDN2 seems to bind to EDNRA on smooth muscle cells of the oviduct.…”