Characterization of a coronary vasoconstrictor produced by cultured endothelial cells

Abstract

The vasoactive effects of media obtained from bovine aortic endothelial cells (EC) in culture were directly tested on isolated rings of the porcine left anterior descending coronary artery. Increasing concentrations of EC-conditioned culture media resulted in progressive dose-dependent increments in isometric tension in porcine, bovine, and canine coronary arteries; the response did not require an intact endothelium. Control (nonconditioned) media and that conditioned by fibroblasts or vascular smooth muscle cells in culture had negligible effects on vessel tone. The vasoconstriction required extracellular Ca2+ and was unaffected by inhibitors of cyclooxygenase and lipoxygenase or by antagonists to the alpha- or beta-adrenergic, serotonergic, histaminergic, or cholinergic receptor systems. Calibrated gel filtration of the media indicated a molecular weight of 8,500 for the vasoactive factor; treatment of the EC-conditioned media with either sodium dodecyl sulfate, trypsin, alkali, or with acid hydrolysis completely abolished the vasoconstrictive effect. These findings and others now provide evidence for the existence of an EC-derived polypeptide vasoconstrictor that may be important in the regulation of vascular smooth muscle contractility.

Effects of ACE-Inhibitors and Angiotensin Receptor Blockers on Inflammation

“…Since the first identification in 1985 by Hickey et al [40] of a vasoconstrictor peptide secreted by endothelial cells, today the endothelin system includes several peptides produced by many organs. ET-1 is the most abundant and important ET produced by vascular cells.…”

A virtual-system coupled multicanonical molecular dynamics simulation: Principles and applications to free-energy landscape of protein–protein interaction with an all-atom model in explicit solvent

“…2, we developed a variant of McMD (V-McMD) using the virtual states to enhance sampling more effectively than the original McMD or TTPMcMD, and to compute the free-energy landscape for homodimer formation of an Endothelin-1 (ET1) derivative in explicit solvent. ET1, which is a potent and long-lasting vasoconstrictor on smooth muscles of a vessel, [28][29][30][31] is thought to be an important drug target because it is related to many human diseases. [32][33][34][35][36] Because of its two intra-peptide disulfide bonds, ET1 has a compact tertiary structure in solution.…”

MEK1/2 inhibition attenuates vascular ETA and ETB receptor alterations after cerebral ischaemia

“…Endothelin (ET) is a vasoactive peptide that was first discovered in 1985 by Hickey and colleagues (Hickey et al 1985). Two endothelin receptors have been identified in mammals, the endothelin type A (ET A ) and type B (ET B ) receptors (Arai et al 1990;Sakurai et al 1990).…”