ENDOTHELIN-1 DISPLACES [H-3] NICARDIPINE BINDING IN SECTIONS OF HUMANRENAL-ARTERY

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, the actions o f which are mediated through interaction with specific ET receptors. F unctional evidence has shown that the constrictor effect of ET may req uire extracellular Ca2+. Ca2+ antagonists of the dihydropyridine famil y attenuate the vasoconstriction caused by ET. However, the basis of t he interactions between ET and dihydropyridine agents are not well und erstood. Our study was designed to assess whether different concentrat ions of ET-1 or ET-3 have any effect on [H-3]nicardipine binding to se ctions of human renal artery. [H-3]Nicardipine was specifically bound to sections of the human renal artery. Binding sites, which were locat ed primarily over smooth muscle of the tunica media, showed the pharma cologic profile typical of a dihydropyridine Ca2+ channel. Increasing concentrations of ET-1, but not of ET-3, competed dose-dependently wit h [H-3]nicardipine binding. A 1-nM concentration of ET-1 lessened spec ific [H-3]nicardipine binding by approximately 80%. These results sugg est the occurrence of an interaction in the human renal artery between dihydropyridine Ca2+ channels and ET-1. This interaction probably acc ounts for the inhibition of the ET-1-mediated vasoconstriction elicite d by nicardipine.