Release of endogenous nitric oxide mediates arteriolar dilation to endothelin in rat striated muscle.
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.
Zhao
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Department of Physiology and Biophysics, School of Medicine, University of Louisville, Kentucky 40292, USA.
Joshua
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D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D010456:Peptides, Cyclic; D009569:Nitric Oxide; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D019331:NG-Nitroarginine Methyl Ester