PRE AND POSTMENOPAUSAL HEMODYNAMIC RESPONSES TO ALCOHOL

酒精引起的心血管异常主要表现在 男性和雄性实验动物。 的性别差异 心血管功能和反射使其不合理地推断 在男性和女性人群中的可用结果。 即使在 后者，乙醇的血流动力学效应可能在绝经前和绝经后之间变化。 和绝经后女性，并被同时使用 外源性雌激素作为避孕药或替代疗法， 人口，分别。 拟议的研究将集中在这些方面 问题. 雌激素作为口服避孕药的新兴趣 绝经前妇女和绝经后妇女的替代疗法， 这些妇女中的一些人同时饮酒， 值得注意。 在最近的配方和剂量中，单独给予雌激素或 与孕激素组合发挥有益心血管作用。 鉴于酒精的广泛使用，研究表明， 乙醇对女性心血管功能和反射的影响 人口和相互作用的类型（有利或不利） 酒精和雌激素是必要的 第一个目的是为了支持假设，即急性 乙醇的血液动力学效应受绝经状态的影响。 是否性别相关的差异，在药代动力学的乙醇和 压力感受性反射活动对乙醇血流动力学反应的影响 研究了 第二个目标测试假设：（i）*{慢性 适度饮酒对心脏和血管的影响受以下因素的影响： 绝经状态}*，和（ii）酒精损害保护性心脏和 雌激素替代疗法的血管效应，至少涉及 内皮源性舒张因子一氧化氮。 第三个目标 *{探索的可能性，规模和时间进程的 对适量酒精的慢性血压反应 受更年期的影响 适度饮酒增加 循环雌激素水平，通过芳香化肾上腺雄激素，在外科手术中 绝经期（切除卵巢的妇女或大鼠）。 这些酒精引起的荷尔蒙 预计这些变化将影响其对血液的短期和长期影响， 压力 雌激素和酒精对心血管的保护作用- 绝经后妇女雌激素水平的诱发变化已经被 在雌性大鼠中复制。 因此，拟议研究的结果如下： 预期产生临床相关信息。}* 拟议的研究 旨在测试这些假设在无约束的清醒大鼠 长期使用仪器检测血液动力学、交感神经活动，以及 血液乙醇和雌激素水平测量。 *{拟议的研究重点是适量的血液动力学影响 酒精的卵巢切除大鼠;手术绝经的模型。 在 除了获得关于适度饮酒影响的基本知识外， 使用对女性人群心血管功能的影响， 预期将产生有关血液动力学效应的相关信息， 绝经后妇女适度饮酒。}*

Alcohol-induced cardiovascular anomalies have been demonstrated mainly in men and male experimental animals. Gender-related differences in cardiovascular function and reflexes make it unreasonable to extrapolate available findings in the male to the female population. Even in the latter, the hemodynamic effects of ethanol may vary between premenopausal and postmenopausal women and to be further confounded by the concurrent use of exogenous estrogen as a contraceptive or replacement therapy in the two populations, respectively. The proposed studies will focus on these issues. Renewed interest in estrogen as oral contraceptives in premenopausal women and as replacement therapy in postmenopausal women and the concurrent alcohol use by some of these women make the proposed studies noteworthy. In its recent formulations and dosage, estrogen given alone or in combination with progestins exert beneficial cardiovascular actions. Given the widespread use of alcohol, studies that deal with the action of ethanol on the cardiovascular function and reflexes of the female population and the type of interaction (beneficial or adverse) between ethanol and estrogen are warranted. The first aim is intended to support the hypothesis that the acute hemodynamic effects of ethanol are influenced by the menopausal state. Whether gender-related differences in the pharmacokinetics of ethanol and baroreflex activity influence the hemodynamic responses to ethanol will be investigated. The second aim tests the hypotheses: (i) *{the chronic cardiac and vascular effects of moderate alcohol use are influenced by menopausal state}*, and (ii) alcohol compromises the protective cardiac and vascular effects of estrogen replacement therapy which involve, at least in part, the endothelium-derived relaxing factor nitric oxide. The third aim *{ explores the possibility that the magnitude and time-course of the chronic blood pressure responses to moderate amounts of alcohol are influenced by the menopausal state. Moderate alcohol use increases circulating estrogen levels, by aromatizing adrenal androgens, in surgical menopause (ovariectomized women or rats). These alcohol-evoked hormonal changes are expected to influence its short and long term effects on blood pressure. The cardiovascular protective effects of estrogen and alcohol- evoked changes in estrogen levels in postmenopausal women have been replicated in female rats. Therefore, findings of the proposed studies are expected to yield clinically relevant information.}* The proposed studies are intended to test these hypotheses in unrestrained conscious rats chronically instrumented for hemodynamic, sympathetic neural activity, and blood ethanol and estrogen level measurements. *{The proposed study focuses on the hemodynamic effects of moderate amounts of alcohol in the ovariectomized rat; a model for surgical menopause. In addition to gaining basic knowledge about the effects of moderate alcohol use on the cardiovascular function of the female population, the studies are expected to yield relevant information on the hemodynamic effects of moderate alcohol use in postmenopausal women.}*