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.
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