CENTRALLY MEDIATED CARDIOVASCULAR EFFECTS OF ETHANOL

大量流行病学和对照临床研究的结果 表明长期饮酒会增加患病率 以及高血压的严重程度。血管紧张素转换酶的升压和心动过速效应 乙醇在实验动物中也被记录在案，但 这些效应背后的机制尚不清楚。乙醇可以影响 心血管系统不仅通过对心脏的直接作用和 血管系统，但也通过心血管调节部位的作用 在中枢神经系统中。压力感受器反射是最 维持血压和心脏的重要动态平衡机制 心率在正常的生理范围内。最近在老鼠身上的研究已经 显示急性和慢性酒精治疗都抑制 压力感受性反射通过作用于脑干的一个或多个部位来反应心动过缓。 孤束核(NTS)是孤束核第一次突触的部位。 压力感受性反射弧和邻近的背侧运动核 迷走神经(DVN)和疑核也是 额外的传入输入，调节、抑制或促进 压力反射。我们的工作假设是乙醇抑制压力感受器反射 通过增强内源性抑制机制和/或通过 抑制脑干的内源性促进机制。主 NTS/DVN的抑制机制是GABA能，而内啡肽能 来自下丘脑的输入可以促进压力感受性心动过缓。我们的 先前的研究表明，乙醇抑制压力感受性心动过缓。 部分通过增强内源性GABA在NTS/DVN中的类似作用， 我们还表明，乙醇可以抑制细胞的活性。 下丘脑内啡肽能神经元系统。目前的建议是 进一步阐明GABA和β-内啡肽在压力感受器反射中的作用 乙醇的抑制作用。我们将研究乙醇对人体健康的影响 心血管对刺激不同神经通路的反应 已知的是撞击并激活大脑中的GABA能中间神经元 NTS/DVN和核歧义。我们将测试乙醇对乙醇的影响。 具有差异敏感性的选择性繁殖大鼠的压力感受性反射 对乙醇的急性效应，包括对GABA门控的增强 氯化物熔剂。最后，我们将研究可能扮演的角色 内啡肽能神经传入NTS对压力感受性反射的抑制作用 乙醇。

The results of numerous epidemiological and controlled clinical studies indicate that chronic ethanol consumption increases both the prevalence and severity of hypertension. The pressor and tachycardiac effects of ethanol have been also documented in experimental animals, but the mechanisms underlying these effects are not clear. Ethanol can influence the cardiovascular system not only by a direct action on the heart and vasculature, but also by an action at sites of cardiovascular regulation in the central nervous system. The baroreceptor reflex is the most important homeostatic mechanism for maintaining blood pressure and heart rate within normal, physiological limits. Recent studies in the rat have demonstrated that both acute and chronic treatment with ethanol inhibit baroreflex bradycardia by acting at one or more sites in the brainstem. The nucleus tractus solitarii (NTS) is the site of the first synapse of the baroreflex arc and, together with the adjacent dorsal motor nucleus of the vagus (DVN) and nucleus ambiguous, are also sites of integration for additional afferent input that modulates, inhibits or facilitates, the baroreflex. Our working hypothesis is that ethanol inhibits baroreflex bradycardia by potentiating an endogenous inhibitory mechanism, and/or by inhibiting an endogenous facilitatory mechanism in the brainstem. The main inhibitory mechanism in the NTS/DVN is GABAergic, while endorphinergic input from the hypothalamus can facilitate baroreflex bradycardia. Our previous studies indicate that ethanol inhibits baroreflex bradycardia in part by potentiating the similar action of endogenous GABA in the NTS/DVN, and we have also shown that ethanol inhibits the activity of the hypothalamic endorphinergic neuronal system. The present proposal is to further clarify the role of GABA and beta-endorphin in the baroreflex inhibitory action of ethanol. We will examine the effects of ethanol on the cardiovascular responses to stimulation of various neural pathways that are known to impinge on and activate GABAergic interneurons in the NTS/DVN and nucleus ambiguous. We will test the effect of ethanol on the baroreflex in selectively bred rats that display differential sensitivity to the acute effects of ethanol, including the potentiation of GABA-gated chloride fluxes. Finally, we will examine the possible role of endorphinergic neural input to the NTS in the baroreflex inhibitory effect of ethanol.