CHRONIC CORONARY OCCLUSION, EXERCISE TRAINING AND NO

描述(改编自申请人的摘要)：实验 该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 慢性运动对各种必要细胞生化事件的影响 对于一氧化氮的产生：1)通过改变 细胞内钙离子将被检测；2)血管生成之间的协同作用 生长因子、血管内皮生长因子和碱性成纤维细胞 将检测生长因子和内皮功能；3)调节 将对超氧化物歧化酶进行评估，以确定如何产生 超氧阴离子自由基可能与一氧化氮的生物利用度或稳定性有关 氧化物；4)质膜小窝微域的调节；5) 控制一氧化氮的这些不同方面(具体目标1-4)将是 比较雄性和雌性动物来源的血管。这些措施的结果 实验将确定潜在的内皮机制和作用部位 这可能暗示着优化血液的潜在新的治疗方向 流向慢性冠状动脉远端侧支依赖的心肌 冠状动脉疾病患者的血管闭塞。

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.