Dependence of endothelium-mediated relaxation on oxygen and metabolism in porcine coronary arteries.
Dependence of endothelium-mediated relaxation on oxygen and metabolism in porcine coronary arteries.
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猪冠状动脉内皮介导的舒张对氧和代谢的依赖性。
DOI：
10.1152/ajpheart.1993.265.1.h299
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Paul,RJ
中科院分区：
文献类型：
--
作者：
Hashimoto,M;Close,LA;Ishida,Y;Paul,RJ
缺氧对内皮依赖性松弛有重要影响。为了进一步了解潜在的机制，我们研究了离子载体A-23187或激动剂P物质（SP）或凝血酶（TB）在猪冠状动脉中引起的内皮依赖性松弛的O2依赖性。a -23187引起KCl-或u -46619诱导的收缩的内皮依赖性松弛，可以用快速和慢相来描述。松弛的持续时间是剂量依赖性的。SP （10 nM）和TB （0.1 U/ml）也能引起内皮依赖性的快速但短暂的松弛。低氧条件（95% N2-5% CO2代替95% O2-5% CO2， PO2 < 1%）消除了A-23187快速相和SP、TB瞬态弛豫，但没有消除A-23187慢相。快速相的阈值PO2约为35 mmHg。用氰化物（5 mM）预处理，抑制呼吸，或2-脱氧-d -葡萄糖，抑制糖酵解，效果不大。同样，心得安（10微米）或吲哚美辛（10微米）对A-23187、TB或SP的松弛没有影响。相反，一氧化氮合成抑制剂和乌阿班都减弱了所研究的所有内皮依赖性松弛。我们的研究结果表明，A-23187、SP和TB的快速弛缓对O2敏感，但对线粒体呼吸不敏感。然而，a -23187诱导的缓慢持续松弛的特点是对O2的敏感性不同于快速期，但依赖于完整的内皮，并受到NO合成抑制剂的影响。因此，内皮依赖性松弛到A-23187可能是由NO介导的，但其对O2的敏感性表明可能涉及两种不同的机制。
Hypoxia has major effects on endothelium-dependent relaxation. To further understand the underlying mechanism(s), we investigated the O2 dependence of the endothelium-dependent relaxations elicited by ionophore A-23187 or agonists substance P (SP) or thrombin (TB) in porcine coronary arteries. A-23187 elicits an endothelium-dependent relaxation of KCl- or U-46619-induced contractures that can be described in terms of a rapid and slow phase. The duration of the relaxation was dose dependent. SP (10 nM) and TB (0.1 U/ml) also elicited endothelium-dependent relaxations that were rapid but transient. Hypoxic conditions (95% N2-5% CO2 instead of 95% O2-5% CO2; PO2 < 1%) abolished the A-23187 rapid phase and the SP and TB transient relaxation but not the A-23187 slow phase. Threshold PO2 for the rapid phase was approximately 35 mmHg. Pretreatment with cyanide (5 mM), to inhibit respiration, or 2-deoxy-D-glucose, to inhibit glycolysis, had little effect. Similarly, propranolol (10 microM) or indomethacin (10 microM) had no effect on the relaxation to A-23187, TB, or SP. In contrast, both NO synthesis inhibitors and ouabain blunted all endothelium-dependent relaxations studied. Our results suggest that the rapid relaxations to A-23187, SP, and TB are sensitive to O2 but not mitochondrial respiration. The slow sustained relaxation induced by A-23187, however, is characterized by a sensitivity to O2 that is distinct from that of the rapid phase, yet is dependent on an intact endothelium and is affected by NO synthesis inhibitors. Thus the endothelium-dependent relaxation to A-23187 is probably mediated by NO, but its sensitivity to O2 suggests that two distinct mechanisms may be involved.