PRE AND POSTMENOPAUSAL HEMODYNAMIC RESPONSES TO ALCOHOL

酒精引起的心血管异常主要表现在 男人和雄性实验动物。与性别有关的差异 心血管功能和反射使外推是不合理的 在男性和女性人群中可获得的研究结果。即使是在 后者，酒精的血流动力学效应在绝经前可能有所不同。 和绝经后妇女，并因同时使用而进一步混淆 外源性雌激素作为避孕或替代疗法在这两个国家 分别为种群数量。拟议的研究将集中在以下方面 问题。人们对雌激素作为口服避孕药重新产生了兴趣 绝经前妇女和绝经后妇女的替代疗法 其中一些女性同时饮酒进行了拟议的研究 值得注意的是。在其最近的配方和剂量中，雌激素单独或 与孕激素联合使用，发挥有益的心血管作用。 鉴于酒精的广泛使用，涉及酒精作用的研究 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) 乙醇和雌激素是必要的。 第一个目的是为了支持这样的假设，即急性 乙醇的血流动力学效应受绝经状态的影响。 乙醇和乙醇的药代动力学是否存在性别差异 压力感受器反射活动影响对酒精的血流动力学反应 调查过了。第二个目的是检验假设：(I)*慢性 适度饮酒对心脏和血管的影响受 更年期状态*，和(Ii)酒精损害保护心脏和 雌激素替代疗法的血管效应，至少涉及 部分，内皮细胞衍生的松弛因子一氧化氮。第三个目标 *{探索以下情况的可能性 慢性血压对适量酒精的反应是 受更年期状态的影响。适度饮酒增加 外科手术中肾上腺雄激素芳香化的循环雌激素水平 更年期(去卵巢的妇女或大鼠)。这些由酒精引起的荷尔蒙 预计变化将影响其对血液的短期和长期影响 压力。雌激素和酒精的心血管保护作用- 绝经后妇女雌激素水平的诱发性变化 在雌性大鼠身上复制。因此，建议的研究结果如下 预计将产生临床相关信息。}*拟议的研究 是为了在不受约束的清醒大鼠身上测试这些假设 长期监测血液动力学、交感神经活动，以及 血液酒精和雌激素水平测量。 *{拟议的研究重点是适量摄入对血液动力学的影响 去卵巢的大鼠的酒精含量；外科更年期的模型。在……里面 除了获得有关中度酒精影响的基本知识外 对女性人群心血管功能的利用，研究 有望提供关于血液动力学影响的相关信息 绝经后妇女适量饮酒。

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.}*