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      Endothelin-1-Induced Constriction Inhibits Nitric-Oxide-Mediated Dilation in Isolated Rat Resistance Arteries

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          Abstract

          Vascular endothelial cells release dilatory compounds like nitric oxide and prostacyclin, as well as contractile factors like endothelin-1 (ET-1). We investigated the interaction of ET-1 with nitric-oxide-mediated dilation in cannulated pressurized (75 mm Hg) arterioles from rat cremaster muscle (180 ± 3 µm). Arterioles constricted spontaneously to 101 ± 3 µm, while ET-1 (0.4 n M)increased constriction to 78 ± 3 µm. Acetylcholine, an endothelium-dependent nitric-oxide-mediated vasodilator induced a dose-dependent dilation during spontaneous tone. After addition of ET-1, the response to acetylcholine was significantly impaired. Nitroprusside, an endothelium-independent nitric oxide donor, induced a dose-dependent dilation that was almost completely inhibited by ET-1. In contrast, 8-Br-cGMP-induced dilation was unaffected. Thus, ET-1 appears to inhibit nitric-oxide-mediated dilation at the level of cGMP formation or degradation. The effect of ET-1 appears to be specific for nitric oxide as responses to a prostacyclin analogue were impaired at low doses only. The inhibitory effect of ET-1 on nitric-oxide-mediated dilation could be mimicked with high potassium (65 ± 6 µm), but not with phenylephrine (74 ± 8 µm)-induced constriction. These data show a direct inhibitory effect of ET-1 on nitric-oxide-mediated dilation in isolated skeletal muscle arterioles.

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          Author and article information

          Journal
          JVR
          J Vasc Res
          10.1159/issn.1018-1172
          Journal of Vascular Research
          S. Karger AG
          1018-1172
          1423-0135
          1997
          1997
          24 September 2008
          : 34
          : 6
          : 418-424
          Affiliations
          Laboratory for Physiology, Vrije Universiteit, Amsterdam, The Netherlands
          Article
          159252 J Vasc Res 1997;34:418–424
          10.1159/000159252
          9425994
          © 1997 S. Karger AG, Basel

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          Page count
          Pages: 7
          Categories
          Research Paper

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