Mechanisms underlying diabetes enhancement of endothelin-1-induced contraction in rabbit basilar artery

Abstract

The influence of alloxan-induced diabetes on the reactivity of rabbit basilar artery to endothelin-1 was examined. Endothelin-1 induced concentration-dependent contraction of basilar arteries that was higher in diabetic than in control rabbits. Endothelium removal produced a higher enhancement of the endothelin-1-induced contraction in control than in diabetic rabbits. N G-nitro- l-arginine ( l-NOArg) enhanced the maximal contraction induced by endothelin-1 in control rabbits and potentiated this response in diabetic rabbits. Endothelin ET A receptor antagonist, cyclo( d-Asp-Pro- d-Val-Leu- d-Trp) (BQ-123), inhibited endothelin-1-induced contraction in both rabbit groups. Endothelin ET B receptor antagonist, 2,6-Dimethylpiperidinecarbonyl-γ-Methyl-Leu-N in-(Methoxycarbonyl)- d-Trp- d-Nle (BQ-788), enhanced endothelin-1-induced contraction in control rabbits and decreased the potency of endothelin-1 in diabetic rabbits. Sodium nitroprusside-induced relaxation of basilar arteries was lower in diabetic than in control rabbits. These results suggest that mechanisms underlying rabbit basilar artery hyperreactivity to endothelin-1 include decreased endothelial modulation of endothelin-1-induced contraction, with impaired endothelial endothelin ET B receptor activity; decreased sensitivity to nitric oxide (NO) in vascular smooth muscle; and enhanced participation of muscular endothelin ET A and ET B receptors.