Nitric oxide is the mediator of both endothelium-dependent relaxation and hyperpolarization of the rabbit carotid artery
Nitric oxide is the mediator of both endothelium-dependent relaxation and hyperpolarization of the rabbit carotid artery
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DOI：
10.1073/pnas.94.8.4193
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发表时间：
1997-04-15
影响因子：
11.1
通讯作者：
Garland, CJ
中科院分区：
文献类型：
--
作者：
Cohen, RA;Plane, F;Garland, CJ
内皮依赖性超极化是由内皮细胞释放一氧化氮（NO）还是其他因素引起的，目前还存在争议，因为在许多动脉中，内皮依赖性舒张和超极化抵抗NO合酶的抑制剂。用电化学和化学发光技术检测NO对乙酰胆碱诱导的兔颈动脉内皮依赖性超极化和舒张的贡献。在苯肾上腺素的存在下，去极化和收缩平滑肌细胞，乙酰胆碱引起浓度依赖性的超极化和松弛，这是密切相关的NO的释放。N-ω-硝基-L-精氨酸甲酯（30 μ M）部分减少NO的释放，并引起类似的减少平滑肌细胞松弛和超极化。为了确定残余反应是否由另一种内皮衍生的介质介导或尽管用N-ω-硝基-L-精氨酸甲酯处理仍释放的NO介导，加入N-ω-硝基-L-精氨酸（300 μ M）。联合抑制剂进一步减少，但没有消除，NO释放，平滑肌松弛，和超极化。在抑制剂存在下，对乙酰胆碱的超极化和松弛与NO的释放密切相关。此外，NO供体SIN-1引起超极化和弛豫，这与其释放的NO浓度相关。这些研究表明：（i）即使在高浓度下使用时，这些NO合酶抑制剂也仅部分抑制乙酰胆碱释放NO，（ii）NO而不是另一种因素完全解释了兔颈动脉的内皮依赖性反应。
It is controversial whether the endothelial cell release of nitric oxide (NO) or a different factor(s) accounts for endothelium-dependent hyperpolarization, because in many arteries endothelium-dependent relaxation and hyperpolarization resists inhibitors of NO synthase. The contribution of NO to acetylcholine-induced endothelium-dependent hyperpolarization and relaxation of the rabbit carotid artery was determined by measuring NO with electrochemical and chemiluminescence techniques. In the presence of phenylephrine to depolarize and contract the smooth muscle cells, acetylcholine caused concentration-dependent hyperpolarization and relaxation which were closely correlated to the release of NO. N-omega-nitro-L-arginine methyl ester (30 mu M) partially reduced the release of NO and caused a similar reduction in smooth muscle cell relaxation and hyperpolarization. To determine if the residual responses were mediated by another endothelium-derived mediator or NO released despite treatment with N-omega-nitro-L-arginine methyl ester, N-omega-nitro-L-arginine (300 mu M) was added. The combined inhibitors further reduced, but did not eliminate, NO release, smooth muscle relaxation, and hyperpolarization. Hyperpolarization and relaxation to acetylcholine remained closely correlated with the release of NO in the presence of the inhibitors. In addition, the NO donor, SIN-1, caused hyperpolarization and relaxation which correlated with the concentrations of NO that it released. These studies indicate that (i) the release of NO by acetylcholine is only partially inhibited by these inhibitors of NO synthase when used even at high concentrations, and (ii) NO rather than another factor accounts fully for endothelium-dependent responses of the rabbit carotid artery.