HYPOXIC CORONARY VASOSPASM

描述：(根据抽象和具体目标改编)本提案 是一份修订后的续签申请，以进一步说明这些机制的特征 犬基础缺氧内皮(EC)依赖性收缩 急性心肌缺血后冠状动脉和内皮细胞依赖性反应 而不是慢性再灌流血管。具体目标集中在两大方面 领域：a)EC依赖的缺氧性收缩：1)是否产生 血管内皮细胞对一氧化氮(EDRF)或内皮素(ET)的作用或VSM对cGMP的作用 在缺氧条件下参与EC依赖的血管收缩；2) 临界浓度的cGMP是否揭示了细胞内 VSM的缺氧收缩过程；以及B)EC依赖的反应 再灌注损伤后：1)钝化的EC是否依赖 再灌注损伤后的松弛是由于减少了血管活性物质的释放 超极化因子(EDHF)，ET的增强产物，或通过 减少一氧化氮的产生；2)是否损伤 百日咳毒素敏感的EDRF释放有助于急性和 内皮依赖性松弛对聚集血小板的慢性钝化作用 3)关于EC依赖的缺氧性收缩原因的研究 非慢性再灌流的冠状动脉恶化；和4) 无论是使用一氧化氮供体还是使用omega进行慢性治疗- 不饱和脂肪酸对EC依赖性改变的影响 形成的元件对 再灌注后血管内皮细胞。提出了常规技术 测量完整和裸犬冠脉等长张力的方法 动脉、一氧化氮、ET、cGMP，以及级联生物测定 或“三明治”制剂，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.