Effect of endothelin-1 on calcium channel gating by agonists in vascular smooth muscle.

Rat isolated aorta was more sensitive to the contractile effect of endothelin-1 (ET-1) when the endothelium was removed. ET-1 was more potent on mesenteric resistance arteries than on aorta. A threshold concentration of ET-1 (100 pM) enhanced the contractile responses of aortic rings to Bay K 8644 and clonidine, especially in the absence of endothelium. Potentiation of clonidine-evoked contraction was accompanied by an enhancement of 45Ca influx and was abolished by nifedipine. These actions of ET-1 (100 pM) could not be attributed to a decrease in membrane potential or in cAMP levels. ET-1 (100 pM) decreased cGMP in intact aortic rings, which could contribute to its actions in the presence of endothelium. Removal of endothelium reduced cGMP levels and these were not further decreased by ET-1. Since ET-1 exerted a pronounced potentiating effect in the absence of endothelium, it is likely that ET-1 modulates calcium channels by an additional mechanism, unrelated to cyclic nucleotides.