OPENING LECTURE: PDF OnlyWong-Dusting H. K.; La, M.; Rand, M. J.Journal of Cardiovascular Pharmacology: 1991 - p S233-238 Free Abstract Summary 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 n M) and in a concentration that increased the perfusion pressure by 70 mm Hg (1 n M), 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 n M). In contrast, higher concentrations of ET-1 (3 and 10 n M) 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. © Lippincott-Raven Publishers.