SEX DIFFERENCES IN CARDIOVASCULAR, HEMODYNAMIC, AND CELLULAR EFFECTS OF COCAINE

社会上药物滥用的普遍程度，加上 黑人高血压的发病率，已被证明是有害的， 这部分人口的健康和社会福利。 的 滥用物质对女性的影响，因为它与 不同药剂的作用尚未充分探讨。 的 拟议研究的目标是：a）评估性别平等 在心血管、代谢、神经内分泌、 交感神经和血液动力学反应的急性和亚慢性影响 B）评估可卡因在Dahl品系大鼠中的性别差异; 可卡因对神经内分泌的影响; c）评估 可卡因对类花生酸释放及血管内皮的影响 依赖性舒张因子（如一氧化氮）; d）评估性别 可卡因对细胞增殖影响的差异。 这些 目标将通过具体的实验来解决，在这些实验中，大鼠将 使用可卡因进行急性和慢性治疗。 间接血液 血压（BP）和心率（HR）将通过尾部测量- 在可卡因之前和之后每周进行体积描记，持续6周 局 还将在给药前和给药后记录体重。 给药后一周。 在实验结束时，直接 将进行BP、HR和离散器官流量的测量。 在 此外，将通过直接测量来评估交感神经活动 血浆中的儿茶酚胺 其他升压系统的影响将是 通过注射不同剂量的去甲肾上腺素（NE）进行评价， 血管紧张素II（A-II）。 这些目标将通过以下方式实现： 将在清醒大鼠中进行BP、HR测量;血流量离散 器官（肾脏、肠系膜和后腿）将使用 具有植入在各自的微探针上的跨音速流量计 动脉（麻醉下显微手术）。 血样检测类花生酸 并从动脉导管中取出血浆儿茶酚胺测定 植入股动脉。 儿茶酚胺和类花生酸，威尔 采用放射酶-薄层色谱法和放射免疫法测定 分别 心血管参数的变化将与 体重的变化。 耐受性的发展程度 可卡因对心血管和血液动力学的影响，如果有的话， 评估。 可卡因对内皮细胞损伤及运动的影响 将使用交互式图像分析系统进行评估， 电镜 从这些研究中获得的数据将提供 对心血管疾病和离散型心血管疾病的性别差异的新见解 可卡因作用涉及的血液动力学和细胞机制。

The prevalence of drug abuse in society, coupled with the higher incidence of hypertension in blacks, has proven to be detrimental to the health and social well being of this segment of the population. The effects of abused substances in females as it relates to mechanism(s) of action of the different agents, has not been adequately explored. The objectives of the proposed studies are; a) to evaluate gender differences on the cardiovascular, metabolic, neuroendocrine, sympathetic and hemodynamic responses to acute and subchronic effects of cocaine in Dahl strain of rats; b) to evaluate gender differences on the neuroendocrine effects of cocaine; c) to evaluate gender differences on the effect of cocaine on release of eicosanoids and endothelium dependent relaxing factor (e.g. nitric oxide); d) to evaluate gender differences on the effect of cocaine on cellular proliferation. These objectives will be addressed by specific experiments in which rats will be treated with cocaine acutely and chronically. Indirect blood pressure (BP) and heart rate (HR) will be measured by tail- plethysmography prior to and every week for six weeks following cocaine administration. Body weights will also be recorded prior to and every week after drug administration. At the end of the experiments, direct measurements of BP, HR and discrete organ flow will be carried out. In addition, sympathetic activity will be assessed by direct measurements of plasma catecholamines. The effects of other pressor systems will be evaluated by injection of different doses of norepinephrine (NE) and angiotensin II (A-ll). These aims will be achieved as follows; Direct measure of BP, HR will be done in conscious rats; blood flow to discrete organs (renal, mesenteric and hindquarters) will be done using a Transonic flowmeter with microprobes implanted on the respective arteries (microsurgery under anesthesia). Blood samples for eicosanoids and plasma catecholamine assay will be withdrawn from arterial catheters implanted in the femoral arteries. Catecholamines and eicosanoids, will be assayed by the radioenzymatic - TLC method and RIA method respectively. Changes in cardiovascular parameters will be correlated with changes in body weight. The degree of development of tolerance to the cardiovascular and hemodynamic effects of cocaine, if any, will be assessed. The effect of cocaine on endothelial cell injury and motility will be evaluated using an interactive image analysis system and electron microscopy. The data derived from these studies will provide new insights in gender differences on the cardiovascular and discrete hemodynamic and cellular mechanisms involved in the actions of cocaine.