Release of endogenous nitric oxide mediates arteriolar dilation to endothelin in rat striated muscle.

Abstract

Previous studies demonstrated that endothelin-1 is a potent vasoconstrictor in the microcirculation. In this study, we assessed the ability of endothelin-1 to induced dilation of small arterioles in the rat cremaster muscle. Responses to topical application of endothelin-1 were assessed by using intravital microscopy. Exposure to increasing concentrations of endothelin-1 (10[-13]-10[-8] M) produced a dose-dependent constriction of third-order arterioles (20 +/- 1.4 microm). Pretreatment with hydroquinone (HQ) or N omega-nitro-L-arginine methyl ester (L-NAME), antagonists of nitric oxide production, caused a significant potentiation in the reactivity of third-order arterioles to endothelin-1. In addition, we observed a significant vasodilation to low levels of endothelin-1 (10[-14]-10[-12] M) in the presence of the endothelin type-A receptor (ET-A) antagonist, BQ123. This dilation was abolished in the presence of a 10(-4) M bath concentration of L-NAME. These results indicated that endothelin-1 caused arteriolar dilation by stimulating endogenous production of nitric oxide. This effect appeared to attenuate the constrictor effects of endothelin-1 on small resistance vessels in striated muscle.