HYPOXIC CORONARY VASOSPASM

描述：（根据抽象和具体目标改编）本提案 是一个经过修订的更新应用程序，以进一步描述机制 犬缺氧内皮依赖性收缩 急性心肌缺血后冠状动脉和EC依赖性反应 与慢性再灌注血管相比。 具体目标集中在两个主要方面 领域：A）EC依赖性缺氧收缩：1）是否生产 内皮细胞测定一氧化氮（EDRF）或内皮素（ET），VSM测定cGMP 在缺氧条件下参与EC依赖性血管收缩; 2） cGMP的临界浓度是否揭示了 缺氧引起的VSM收缩过程;和B）EC依赖性反应 再灌注损伤后：1）是否钝化EC依赖性 再灌注损伤后舒张 是由于减少释放 OFA 超极化因子（EDHF），ET的增加产生，或通过 减少一氧化氮的产生; 2）是否损害 百日咳毒素敏感的EDRF释放有助于急性和 内皮依赖性舒张对聚集血小板的慢性钝化 3）研究EC依赖性缺氧收缩 慢性再灌注冠状动脉恶化;以及4） 是否用一氧化氮供体长期治疗 或与欧米茄- 不饱和脂肪 酸影响改变的EC依赖性 成形元件对成形元件的响应性和/或响应性， 再灌注后的内皮细胞。 提出了常规技术， 测量完整与裸露犬冠状动脉的等长张力 动脉，一氧化氮，ET，cGMP，以及级联生物测定 或“夹心”制备以及可能的细胞培养方法。

DESCRIPTION: (Adapted from the abstract and specific aims) This proposal is a revised renewal application to further characterize the mechanisms underlying anoxic endothelium (EC)-dependent contractions of canine coronary arteries and EC-dependent responses following ischemia in acute versus chronic reperfused vessels. Specific aims focus on two major areas: A) EC-dependent anoxic contractions: 1) Whether the production of nitric oxide (EDRF) or endothelin (ET) by ECs or cGMP by VSM participate in EC-dependent vasoconstriction under anoxic conditions; 2) Whether a critical concentration of cGMP unmasks an activation of the contractile process in VSM by anoxia; and B) EC-dependent responses after reperfusion injury: 1) Whether the blunted EC-dependent relaxation after reperfusion injury is dueto reduced release ofa hyperpolarizing factor (EDHF), an augmented production of ET, or by reduced production of nitric oxide; 2) Whether impairment of the pertussis toxin-sensitive release of EDRF contributes to the acute and chronic blunting of EC-dependent relaxations to aggregating platelets with reperfusion; 3) Studies as to why EC- dependent anoxic contractions are exacerbated inchronically reperfused coronary arteries; and 4) Whether chronic treatment with nitric oxide donors or with omega- unsaturated fatty acids influence altered EC-dependent responsiveness and/or adhesiveness of formed elements to the endothelium after reperfusion. Conventional techniques are proposed to measure isometric tension in intact versus denuded canine coronary arteries, nitric oxide, ET, cGMP, as well as bioassays in cascade or "sandwich" preparations, and possible cell culture methodologies.