Endothelin-1-induced constriction inhibits nitric-oxide-mediated dilation in isolated rat resistance arteries.
Endothelin-1-induced constriction inhibits nitric-oxide-mediated dilation in isolated rat resistance arteries.
复制标题
内皮素-1 诱导的收缩抑制离体大鼠阻力动脉中一氧化氮介导的扩张。
DOI：
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发表时间：
1997
影响因子：
1.7
通讯作者：
P. Sipkema
中科院分区：
文献类型：
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作者：
E. Bakker;P. V. D. van der Linden;P. Sipkema
血管内皮细胞释放一氧化氮和前列环素等扩张化合物，以及内皮素-1 (ET-1) 等收缩因子。我们研究了 ET-1 与大鼠提睾肌（180 +/- 3 微米）的插管加压（75 毫米汞柱）小动脉中一氧化氮介导的扩张的相互作用。小动脉自发收缩至 101 +/- 3 微米，而 ET-1 (0.4 nM) 将收缩增加至 78 +/- 3 微米。乙酰胆碱是一种内皮依赖性一氧化氮介导的血管舒张剂，在自发张力期间诱导剂量依赖性扩张。添加ET-1后，对乙酰胆碱的反应显着受损。硝普钠是一种不依赖于内皮细胞的一氧化氮供体，可诱导剂量依赖性扩张，而这种扩张几乎完全被 ET-1 抑制。相反，8-Br-cGMP 诱导的扩张不受影响。因此，ET-1 似乎在 cGMP 形成或降解水平上抑制一氧化氮介导的扩张。 ET-1 的作用似乎对一氧化氮具有特异性，因为仅在低剂量时才会损害对前列环素类似物的反应。 ET-1 对一氧化氮介导的扩张的抑制作用可以用高钾 (65 +/- 6 微米) 来模拟，但不能用去氧肾上腺素 (74 +/- 8 微米) 诱导的收缩来模拟。这些数据显示 ET-1 对离体骨骼肌小动脉中一氧化氮介导的扩张具有直接抑制作用。
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 microm). Arterioles constricted spontaneously to 101 +/- 3 microm, while ET-1 (0.4 nM) increased constriction to 78 +/- 3 microm. 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 microm), but not with phenylephrine (74 +/- 8 microm)-induced constriction. These data show a direct inhibitory effect of ET-1 on nitric-oxide-mediated dilation in isolated skeletal muscle arterioles.