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 i s 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.}*
