CHRONIC CORONARY OCCLUSION, EXERCISE TRAINING AND NO

描述（改编自申请人的摘要）：此实验 该提案将研究运动训练如何影响一氧化氮的调节 因慢性冠状动脉闭塞而产生的冠状动脉侧支循环 小型猪。提出了五个具体目标来系统评估 长期运动对各种细胞生化事件的影响是必要的 对于一氧化氮的产生： 1) 通过变化来调节一氧化氮 将检查细胞内钙； 2）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以确定如何产生 超氧自由基可能与硝酸的生物利用度或稳定性有关 氧化物； 4) 将检查质膜小凹微区的调节； 5） 一氧化氮控制的各个方面（具体目标 1-4）将 比较来自雄性和雌性动物的血管。这些结果 实验将确定潜在的内皮机制和作用位点 这可能暗示优化血液的潜在新治疗方向 流向慢性冠状动脉远端的侧支依赖性心肌 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.