Different utilization of Ca2+ in the contractile action of endothelin-1 on cerebral, coronary and mesenteric arteries of the dog

Abstract

Vasoconstrictor responses to endothelin-1 (ET) were compared between endothelium-denuded strips of cerebral, coronary and mesenteric arteries of the dog. Contractile responses to lower concentrations (below 3 x 10(-10) M) of ET were significantly greater in the cerebral and coronary arteries than in the mesenteric artery. The cerebral and coronary arteries, but not the mesenteric artery, relaxed significantly from the resting level when placed in a 0-Ca solution. Readdition of Ca2+ to the cerebral and coronary arteries placed in the 0-Ca solution caused a biphasic contraction which was susceptible to inhibition by nifedipine. When ET below 10(-10) M was introduced before the Ca2+ contraction, this peptide produced no detectable contraction, but augmented the Ca2+ contraction. The augmented Ca2+ contractions were abolished by 10(-7) M nifedipine. These effects of ET were not observed in the mesenteric artery. The contractile responses of the mesenteric artery to ET determined in the presence of elevated extracellular K+ concentrations were comparable to the responses of the cerebral artery to this peptide determined in the presence of normal K+ concentrations. These results indicate that the enhanced responses to ET in the cerebral and coronary arteries were dependent on the Ca2+ influx through voltage-dependent Ca2+ channels and suggest that these channels are in an activated state when these arteries are in a resting state.