CORONARY VASCULAR EFFECTS OF ENVIRONMENTAL STIMULI

环境刺激现在被认为是重要的贡献者 心血管疾病然而，作用的机制和部位 介导心肌缺血、心律失常和突发性心律失常的进展， 由环境刺激如行为应激引起的心源性死亡 和高盐饮食是不了解的。(The拟议的研究将测试 假设行为应激和高盐饮食可以独立地， 并且两者结合，损害冠状血管舒张。 清醒 正常血压Wistar京都大鼠（WKY）、临界高血压大鼠（BHR） 和自发性高血压大鼠（SHR），动脉压和心脏 将在暴露于空气射流应力的10天期间监测速率，高 NaCl饮食，或喷气应激和高NaCl饮食的组合。在 10天结束时，将评估冠状动脉血管功能的变化 通过测定离体冠状动脉的血管反应性改变 在体外，并通过评估冠状动脉血流速度的变化， 体内血管活性剂的作用。 初步研究表明， 行为暴露对BHR和SHR冠状动脉舒张的影响 应力在BHR的实验研究表明，无论是行为 压力或高盐饮食可产生高血压， 增加血浆儿茶酚胺水平和增强交感神经 系统活动。在拟议的研究中，α和β肾上腺素受体 拮抗剂，抑制去甲肾上腺素的神经元释放， 将在体内使用肾上腺髓质，以评估增强的 交感神经系统在冠状动脉病变中的活动 由环境刺激产生的反应。此外，机制 介导受损的内皮依赖性冠状动脉舒张将是 体外测定。有待检验的机制包括： L-精氨酸，B）受损的一氧化氮合酶，c）降低对 一氧化氮，d）通过超氧化物增强一氧化氮的失活 阴离子，e）降低对环GMP的敏感性，和f）增强灭活 环GMP磷酸二酯酶的环GMP。这些研究将提供 关于环境刺激在发展中作用的新信息 冠状动脉疾病和介导这一过程的机制。这 可以更有效地预防疾病和死亡， 冠心病

Environmental stimuli are now recognized as important contributors to cardiovascular disease. However, the mechanisms and sites of action mediating the progression of myocardial ischemia, arrhythmias and sudden cardiac death induced by environmental stimuli such as behavioral stress and high NaCl diet are not understood. (The proposed studies will test the hypothesis that behavioral stress and high NaCl diet can independently, and in combination, impair coronary vasodilation. In conscious normotensive Wistar Kyoto rats (WKY), borderline hypertensive rats (BHR) and spontaneously hypertensive rats (SHR), arterial pressure and heart rate will be monitored during ten days of exposure to air-jet stress, high NaCl diet, or a combination of air-jet stress and high NaCl diet.) At the end of ten days, changes in coronary vascular function will be evaluated by determining altered vascular reactivity of the isolated coronary artery in vitro and by assessing changes in coronary blood flow velocity produced by vasoactive agents in vivo. {Preliminary studies have demonstrated impaired endothelial-dependent relaxation in coronary arteries of BHR and SHR exposed to behavioral stress. Experimental studies in BHR have shown that either behavioral stress or high NaCl diet can produce hypertension which is accompanied by increased plasma catecholamine levels and enhanced sympathetic nervous system activity. In the proposed studies, alpha- and beta-adrenoceptor antagonists, inhibition of neuronal release of norepinephrine, and removal of adrenal medulla will be used in vivo to assess the role of enhanced sympathetic nervous system activity in the altered coronary vascular responses produced by environmental stimuli. Additionally, mechanisms mediating impaired endothelial-dependent coronary relaxation will be determined in vitro. Mechanisms to be tested include: a) a deficiency of L-arginine, b) impaired nitric oxide synthase, c) reduced sensitivity to nitric oxide, d) enhanced inactivation of nitric oxide by superoxide anions, e) reduced sensitivity to cyclic GMP, and f) enhanced inactivation of cyclic GMP by cyclic GMP phosphodiesterase.} These studies will provide new information on the role of environmental stimuli in the development of coronary artery disease and the mechanisms mediating this process. This could lead to more effective prevention of morbidity and mortality from coronary artery disease.