MECHANISMS OF ETHANOL-INDUCED CARDIOVASCULAR PROTECTION

心血管疾病仍然是美国妇女和妇女死亡的主要原因，因此更好地了解心脏保护机制所带来的健康益处可能是巨大的。大量流行病学数据表明，适度饮酒可以降低心血管疾病的发病率和与心肌梗死相关的死亡率。与适度饮酒相关的心脏保护在许多方面类似于晚期预处理，表明它们可能具有共同的但尚未确定的分子机制。酒精的心血管保护作用可分为两大类：（1）对体循环成分（血管和血液成分）的影响，（2）对心肌的影响。这项建议将集中在描绘的机制，对血管的心脏保护作用的酒精。初步数据显示：（1）适量酒精增强血管功能，这是一种心脏保护形式;（2）适量酒精导致血管系统中一氧化氮合酶（NOS）的诱导;（3）NOS的诱导涉及两种亚型，iNOS和eNOS;（4）NO的生物利用度也可通过超氧化物歧化酶（SOD）的诱导而增加;（5）适量饮酒可增加NO的生物利用度，这可能与其心血管保护作用有关。这些数据导致了一种假设，即增加一氧化氮（NO）的生物利用度是一个关键事件的血管和心脏保护事件与慢性中度酒精。将通过完成以下具体目标来检验该假设：（1）与慢性中度乙醇相关的血管保护事件是由于诱导一氧化氮合酶和增加NO的产生导致的NO的生物利用度增加，和（2）与慢性中度乙醇相关的血管保护事件是由于超氧化物增加导致的NO生物利用度增加歧化酶和随后的超氧化物（O2）减少。从这些具体目标的实现所获得的信息将提供深入了解的机制，导致增加的酒精诱导的心血管保护。NO依赖的机制。

Cardiovascular disease remains the leading cause of mortality of both women and women in the United States, so the health benefits gained from a better understanding of the mechanisms of cardioprotection could be enormous. Considerable epidemiological data indicates that moderate alcohol consumption decreases both the incidence of cardiovascular disease and the mortality associated with myocardial infarction. The cardioprotection associated with moderate alcohol consumption is analogous in many ways to late phase pre-conditioning indicating that they may share common, but yet undefined, molecular mechanisms. The cardiovascular protective effects of alcohol can be categorized into two major responses, (1) effects on systemic circulatory components (blood vessels and blood components), (2) effects on myocardium. This proposal will focus on delineating the mechanisms of the cardio-protective effects of alcohol on the vasculature. Preliminary data show that (1) moderate alcohol enhances vascular function, a form of cardioprotection; (2) moderate alcohol results in induction of nitric oxide synthases (NOS) in the vasculature; (3) induction of NOS involves two isoforms, iNOS and eNOS; (4) bioavailability of .NO may also be increased by induction of superoxide dismutases (SOD); (5) increased bioavailability of .NO may be responsibl4e for the cardiovascular protection associated with moderate alcohol consumption. These data have led to the hypothesis that increased nitric oxide (NO) bioavailability is a critical event in the vascular and cardioprotective events associated with chronic moderate alcohol. This hypothesis will be tested by completion of the following Specific Aims: (1) the vascular protective events associated with chronic moderate ethanol are due to the increased bioavailability of .NO resulting from induction of nitric oxide synthases and increased production of .NO and (2) the vascular protective events associated with chronic moderate ethanol are due to the increased bioavailability of .NO resulting from increased superoxide dismutase and a consequent decrease in superoxide (O2). The information gained from the accomplishment of these specific aims will provide insights into the mechanism which lead to increased .NO-dependent mechanisms in alcohol-induced cardiovascular protection.