CORONARY VASCULAR EFFECTS OF ENVIRONMENTAL STIMULI

环境刺激现在被认为是导致 心血管疾病。然而，作用的机制和地点 介导心肌缺血、心律失常和猝发的进展 行为应激等环境刺激所致心源性死亡 和高盐饮食还不是很清楚。(建议的研究将测试 假设行为压力和高盐饮食可以独立存在， 两者结合在一起，会损害冠状动脉血管的扩张。有意识地 血压正常的Wistar京都大鼠(WKY)、临界高血压大鼠(BHR) 和自发性高血压大鼠(SHR)的动脉压和心脏 在暴露在空气喷射压力下的十天内将监测比率，高 氯化钠饮食，或空气喷射应激和高盐饮食的组合。)在 10天后对冠状动脉血管功能的变化进行评估 通过测定离体冠脉的血管反应性 在体外，通过评估冠脉血流速度的变化 通过体内的血管活性物质。 {初步研究表明内皮依赖性受损 行为暴露对BHR和SHR冠脉的松弛作用 压力。BHR的实验研究表明，无论是行为 应激或高盐饮食可产生高血压，并伴有 血浆儿茶酚胺水平升高和交感神经增强 系统活动。在拟议的研究中，α和β肾上腺素能受体 拮抗剂、抑制神经元释放去甲肾上腺素和清除 将在体内使用肾上腺髓质来评估增强的作用 冠状动脉血管病变中的交感神经系统活动 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松弛将是 在体外测定。有待测试的机制包括：a)存在以下缺陷 L-精氨酸，b)损伤一氧化氮合酶，c)降低对 一氧化氮，d)超氧化物增强一氧化氮的失活 阴离子，e)降低了对环GMP的敏感性，以及f)增强了失活 通过环GMP磷酸二酯酶。}这些研究将提供 关于环境刺激在疾病发展中的作用的新信息 冠状动脉疾病及其调节这个过程的机制。这 可以更有效地预防因以下原因引起的发病率和死亡率 冠状动脉疾病。

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.