Cellular mechanism of endothelin-1 release by angiotensin and vasopressin.

Abstract

Release of endothelin-1, a novel potent vasoconstrictor peptide originally isolated from endothelial cells, from cultured bovine endothelial cells has been shown to be stimulated by arginine vasopressin and angiotensin II. To elucidate the cellular mechanism by which endothelin-1 is released by these vasoconstrictors, we tested the effects of several compounds on the agonist-induced endothelin-1 release and studied the changes of cytosolic free Ca peptide with 21-amino acid residues, was originally isolated and sequenced from the supernatant of cultured porcine endothelial cells (ECs).1 ET-1 has not only strong and sustained vasoconstrictive action on a variety of blood vessels from various species 1 -2 but also a wide spectrum of pharmacological effects such as release of eicosanoids and endothelium-derived relaxing factor from perfused vascular beds, 3 aldosterone from cultured calf adrenal zona glomerulosa cells, 4 atrial natriuretic peptide from cultured rat atrial myocytes, 5 and mitogenic action in cultured vascular smooth muscle cells.6 These effects are dependent on extracellular Ca 2+ and inhibited by Ca 2+ channel antagonists, suggesting the importance of Ca 2+ influx in the mechanism of its actions. The induction of preproET-1 messenger RNA (mRNA) in porcine EC is augmented by several agents, such as epinephrine, thrombin, Ca 2+ ionophore, 1 phorbol ester, 8 transforming growth factor (TGF)-/3, 9 cytokines, 10 and shear stress. 11 Our recent studies have shown that two vasoconstrictive hormones, arginine vasopressin (AVP) and angiotensin (Ang) II, also stimulate the release of immunoreactive ET-1 from cultured bovine ECs, and these effects are mimicked by phorbol ester and Ca 2+ ionophore. 12These findings raise the possibility that the AVP-and Ang II-induced ET-1 release from EC may involve a common mechanism (i.e., phosphoinositide breakdown with the resultant mobilization of intracellular Ca 2+ and activation of protein kinase C [PKC]. To address this question, the present study was designed to elucidate the cellular mechanism of AVP and Ang II responsible for ET-1 release in bovine EC. Methods Cell Culture and IncubationECs from bovine carotid artery were prepared by digestion with collagenase and elastase, 13 and culDownloaded from http://ahajournals.org by on April 27, 2019

Role of some vasoactive mediators in patients with erectile dysfunction: their relationship with angiotensin-converting enzyme and growth hormone

“…10 Ang II induces vascular smooth muscle contraction through increasing cytosolic calcium 11 and also it facilitates the secretion of ET-1. 12 Growth hormone (GH) influences the growth and activity of different tissues. It influences the synthesis of insulin-like growth factor I (IGF-1).…”

Renal endothelin in heart failure and its relation to sodium excretion

“…18 In vitro studies have shown that AVP stimulates ppET-1 mRNA expression, 19 and a close correlation has also been reported between AVP plasma levels and urinary ET-1 excretion in volumedepleted exercising healthy subjects. 16 However, stepwise regression analysis revealed that in patients with HF, ANP, BNP, or AVP plasma concentrations were not independently related with urinary ET-1 excretion.…”

“…Angiotensin II has been found to induce ppET-1 mRNA expression and the secretion of mature ET-1 in a dose-dependent manner in cultured bovine, rat, and human endothelial cells. 19 However, although the increased urinary ET-1 excretion observed in normal subjects on a low sodium diet paralleled PRA, ACE inhibition reduced ET-1 excretion by only 20%, 9 thus indicating that in this physiologic setting renal ET-1 formation is largely independent of the RAS. In NYHA class II patients urinary ET-1 excretion was increased despite the absence of PRA increase (Table II).…”

Molecular Pharmacology and Pathophysiological Significance of Endothelin

“…Increased mRNA levels have been observed after treatment of the cells with growth factors and cytokines such as thrombin (13), transforming growth factor (TGF)-r3 (14), tumor necrosis factor (TNF)-a (15), interleukin (IL)-1 (16) and insulin, or with vasoactive substances (17,18) such as norepinephrine, angiotensin II, vasopressin, bradykinin, oxidized or acetylated low density lipoprotein (LDL). The increase in expression of endothelin-1 mRNA induced by thrombin, angiotensin II, and vasopressin has been shown to be promoted by an increase in intracellular Ca 2+ concentration and activation of protein kinase C (PKC) via GTP-binding protein following stimulation of their receptors (13,19). However, the mechanisms of regulation of mRNA expression by other substances remain to be elucidated.…”

“…After more than six years, the cloning and characterization of ECE have finally been successfully achieved. ECE is considered to be a potential target for selectively interrupting the biosynthesis of endothelin; although this approach has proven to be extremely difficult, an N-and C-terminaltruncated analogue of big endothelin-1 , [Phe22] big endothelin-1 [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37], was recently shown to be a potent inhibitor of ECE-1, being at least 30-fold more potent that phosphoramidon in blocking big endothelin-linduced vasoconstriction in the kidney (38).…”