CHRONIC CORONARY OCCLUSION, EXERCISE TRAINING AND NO

描述（改编自申请人的摘要）：本发明的实验 一项提案将研究运动训练如何影响一氧化氮的调节 在慢性冠状动脉闭塞后形成的冠状动脉侧支中， 迷你猪提出了五个具体目标，以系统地评价 慢性运动对各种细胞生化事件的影响 对于一氧化氮的产生：1）通过改变一氧化氮的浓度来调节一氧化氮的产生。 将检查细胞内钙; 2）血管生成和血管生成之间的协同作用， 生长因子、血管内皮生长因子（VEGF）和碱性成纤维细胞 将检查生长因子（bFGF）和内皮功能; 3）调节 将评估超氧化物歧化酶的产生，以确定 超氧自由基可能与硝酸盐的生物利用度或稳定性有关 氧化物; 4）将检查质膜小窝微区的调节; 5） 这些控制一氧化氮的各个方面（具体目标1-4）将被 比较了来自雄性和雌性动物的血管。结果进行 实验将确定潜在的内皮机制和作用部位 这可能暗示了优化血液的潜在新治疗方向， 流向慢性冠状动脉远端侧支依赖性心肌的血流 冠状动脉疾病患者的闭塞。

DESCRIPTION (Adapted from the applicant's abstract): Experiments of this proposal will examine how exercise training affects regulation of nitric oxide in coronary collaterals developed in response to chronic coronary occlusion in miniature swine. Five specific aims are proposed to systematically evaluate the effects of chronic exercise on various cellular biochemical events necessary for nitric oxide production: 1) Regulation of nitric oxide by changes in intracellular calcium will be examined; 2) the synergism between angiogenic growth factors, vascular endothelial growth factor (VEGF), and basic fibroblast growth factors (bFGF) and endothelial function will be examined; 3) regulation of superoxide dismutase will be evaluated to determine how production of superoxide radicals may relate to the bioavailability or stability of nitric oxide; 4) regulation of plasmalemmal caveolae microdomains will be examined; 5) these various aspects of control of nitric oxide (Specific Aims 1-4) will be compared between vessels derived from male and female animals. Results of these experiments will identify underlying endothelial mechanisms and sites of action which may implicate potential new therapeutic directions for optimizing blood flow to collateral-dependent myocardium distal to a chronic coronary artery occlusion in patients with coronary artery disease.