CENTRALLY MEDIATED CARDIOVASCULAR EFFECTS OF ETHANOL

乙醇的中枢介导的心血管作用

• 批准号: 2045969
• 负责人: GEORGE KUNOS
• 金额: $ 15.59万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-01 至 1997-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2045969
• 关键词: GABA receptor; afferent nerve; alcoholic beverage consumption; antihypertensive agents; baroreceptors; centrally acting drug; endorphins; ethanol; genetic strain; heart rate; hypertension; hypothalamus; inhibitor /antagonist; laboratory rat; neuroanatomy; proopiomelanocortin; solitary tract nucleus

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.

许多流行病学和对照临床研究的结果 表明慢性乙醇消费增加了 和高血压的严重程度。的升压和心动过速效应 乙醇在实验动物中也有记录，但 这些影响的机制尚不清楚。乙醇会影响 心血管系统不仅直接作用于心脏， 血管，而且还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 维持血压和心脏重要的稳态机制 在正常的生理范围内。最近在老鼠身上的研究 表明用乙醇进行急性和慢性治疗都抑制了 压力反射性心动过缓通过作用于脑干中的一个或多个部位。 孤束核（NTS）是第一个突触的部位， 压力感受性反射弧，连同邻近的背侧运动核， 迷走神经（DVN）和疑核也是整合的位点， 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 抑制脑干中的内源性易化机制。主要 NTS/DVN的抑制机制是GABA能的，而内啡肽能的 来自下丘脑的输入可促进压力反射心动过缓。我们 以前的研究表明，乙醇抑制压力反射性心动过缓， 部分通过增强NTS/DVN中内源性GABA的类似作用， 我们还发现乙醇会抑制 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-内啡肽在压力感受性反射中的作用 乙醇的抑制作用。我们将研究乙醇对 心血管对各种神经通路刺激的反应 已知它们会影响并激活大脑中的GABA能中间神经元， NTS/DVN和核模糊。我们将测试乙醇对 选择性饲养大鼠的压力感受性反射显示出不同的敏感性 乙醇的急性效应，包括增强GABA门控的 氯化物通量最后，我们将研究 内啡肽能神经输入对孤束核压力感受性反射的抑制作用 乙醇。