Reoxygenation-induced relaxation of coronary arteries. A novel endothelium-dependent mechanism.
Reoxygenation-induced relaxation of coronary arteries. A novel endothelium-dependent mechanism.
复制标题
再氧合引起冠状动脉舒张。
DOI：
10.1161/01.res.74.5.870
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发表时间：
1994
影响因子：
20.1
通讯作者：
Paul,RJ
中科院分区：
文献类型：
--
作者：
Close,LA;Bowman,PS;Paul,RJ
众所周知，冠状动脉收缩力受氧分压调节。平滑肌和内皮细胞都有助于冠状动脉氧敏感性。氧的内皮依赖性作用的潜在机制包括一氧化氮/内皮衍生松弛因子（EDRF）、过氧化氢和类二十烷酸途径的敏感性。在本研究中，我们描述了猪冠状动脉氧敏感性的一种新的内皮依赖性成分，该成分独立于这些已知的途径。用 KCl 或 U46619 刺激猪冠状动脉。缺氧引起了短暂的力量增加，在内皮完整的动脉中这种增加要大得多。这种效应被一氧化氮/EDRF 通路抑制剂 NG-单甲基-L-精氨酸和 N-硝基-L-精氨酸消除。在稳定状态下，缺氧使完整动脉和裸露动脉的等长力降低到相似程度。再氧合仅在完整的动脉中引起快速和短暂的松弛。相比之下，这种内皮依赖性舒张不受一氧化氮/EDRF途径抑制剂的抑制，也不受其他潜在氧敏感途径抑制剂的抑制，例如吲哚美辛、氨基三唑、超氧化物歧化酶、过氧化氢酶、普萘洛尔或哇巴因。然而，复氧弛豫对极低水平的氧气敏感，并受到氰化物和鱼藤酮的抑制，表明线粒体代谢参与其中。有趣的是，与 P 物质类似，通过与内皮完整的供体动脉耦合，可以恢复对再氧合的松弛反应。这个“三明治”实验表明内皮依赖性是由可传递因子介导的。我们的结果表明，一类新型内皮依赖性因子可能有助于冠状动脉对氧分压变化的反应。
Coronary artery contractility is well known to be modulated by oxygen partial pressure. Both smooth muscle and the endothelium contribute to coronary artery oxygen sensitivity. Mechanisms underlying endothelium-dependent effects of oxygen include the sensitivity of the nitric oxide/endothelium-derived relaxing factor (EDRF), hydrogen peroxide, and eicosanoid pathways. In the present study, we characterize a novel endothelium-dependent component of porcine coronary artery oxygen sensitivity that is independent of these known pathways. Porcine coronary arteries were stimulated with either KCl or U46619. Hypoxia elicited a transient increase in force that was much greater in endothelium-intact arteries. This effect was abolished by nitric oxide/EDRF pathway inhibitors NG-monomethyl-L-arginine and N-nitro-L-arginine. In the steady state, hypoxia reduced isometric force to a similar degree in both intact and denuded arteries. Reoxygenation elicited a rapid and transient relaxation only in intact arteries. In contrast, this endothelium-dependent relaxation was not inhibited by nitric oxide/EDRF pathway inhibitors nor inhibitors of other potential oxygen-sensitive pathways, such as indomethacin, aminotriazole, superoxide dismutase, catalase, propranolol, or ouabain. The reoxygenation relaxation was, however, sensitive to very low levels of oxygen and was inhibited by cyanide and rotenone, suggesting an involvement of mitochondrial metabolism. Interestingly, the relaxation response to reoxygenation, similar to that for substance P, could be restored in denuded arteries by coupling with an endothelium-intact donor artery. This "sandwich" experiment suggests that the endothelium dependence is mediated by a transmissible factor. Our results indicate that a novel class of endothelium-dependent factors may contribute to coronary artery responses to changes in oxygen partial pressure.