Vascular mechanism of action of endothelin-1: Effect of Ca2+ antagonists

Journal Article · Sun Jan 01 00:00:00 EST 1989 · Journal of Cardiovascular Pharmacology; (USA)

DOI:https://doi.org/10.1097/00005344-198900135-00009· OSTI ID:5405538

Chabrier, P E; Auguet, M; Roubert, P; Lonchampt, M O; Gillard, V; Guillon, J M; Delaflotte, S; Braquet, P ^[1]

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1. Institut Henri Beaufour, Les Ulis (France)

The vasoconstrictive properties of the endothelium-derived peptide, endothelin-1 (ET-1), were investigated on rat isolated aorta and on cultured rat aortic smooth muscle cells. In rat isolated aorta, endothelin-1 induced a slow and sustained contraction in a Ca2+-free medium; after calcium readmission, an additional sustained contraction was elicited. In vascular smooth muscle cells, endothelin-1 provoked a dose-dependent Ca2+ influx that was not inhibited by calcium entry blockers (nifedipine, D 600, or diltiazem). In these cells, ({sup 125}I)-endothelin-1 bound to a specific, saturable, and high affinity recognition site (Kd about 10(-9) M and Bmax = 52 +/- 2 fmol/10(6) cells). The binding was not reversible and not affected by calcium antagonists. These data do not support the hypothesis that endothelin-1 acts as an endogenous agonist of the voltage-dependent Ca2+ channels. The action of endothelin-1 can be separated into two components: one dependent on Ca2+ influx but insensitive to calcium antagonists and another independent of extracellular Ca2+. The irreversible binding of endothelin-1 may reflect an internalization of the ligand inside the cell membrane, leading to multiple contractile events.

• OSTI ID: 5405538
• Journal Information: Journal of Cardiovascular Pharmacology; (USA), Vol. 13 Suppl 5; ISSN 0160-2446
• Country of Publication: United States
• Language: English

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