Effect of endothelin-1 on responses of isolated blood vessels to vasoconstrictor agonists.
The effect of endothelin-1 (ET-1) on vasoconstrictor responses of the endothelium-denuded perfused rabbit ear artery to 5-hydroxytryptamine (5-HT), histamine, and vasopressin (VP) was studied. In low concentrations with no vasoconstrictor action (0.1 and 0.3 nM), and in a concentration that increased the perfusion pressure by 70 mm Hg (1 nM), ET-1 significantly enhanced responses to the agonists studied; this enhancement was apparently mediated by an increased influx of extracellular calcium through voltage-operated channels, as it was abolished by the calcium channel antagonist nicardipine (10 nM). In contrast, higher concentrations of ET-1 (3 and 10 nM) inhibited responses to VP and 5-HT and this inhibitory effect was accentuated in the presence of nicardipine. The possible mechanism by which ET-1 exerts this inhibitory effect on vasoconstrictor responses is discussed. Because ET-1 is released from endothelial cells that are immediately adjacent to vascular smooth muscle cells, these modulatory effects of ET-1 on responses to endogenously present vasoconstrictors may play a role in vascular function.
Wong-Dusting
H K
HK
Department of Pharmacology, University of Melbourne, Victoria, Australia.
La
M
M
Rand
M J
MJ
D000818:Animals; D001158:Arteries / Q000187:drug effects; D004347:Drug Interactions; D004431:Ear, External / Q000098:blood supply; D016232:Endothelins / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009529:Nicardipine / Q000494:pharmacology; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology
D016232:Endothelins; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D012701:Serotonin; D006632:Histamine; D009529:Nicardipine