ENDOGENOUS GAMMA-AMINOBUTYRIC-ACID (GABA) MEDIATES ETHANOL INHIBITIONOF VAGALLY MEDIATED REFLEX BRADYCARDIA ELICITED FROM AORTIC BARORECEPTORS

We have previously demonstrated that ethanol depresses baro-reflex bra dycardia by potentiating the similar action of endogenous gamma-aminob utyric acid (GABA) in the medullary dorsal vagal complex. In the prese nt study we examined the relative contribution of the sympathetic vs, the parasympathetic nervous sytem and aortic vs. carotid sinus barorec eptors in this effect. Depressor baroreflex responses were elicited in urethane-anesthetized male Sprague-Dawley rats by i.v. injection of g raded bolus doses of phenylephrine or by electrical stimulation of the aortic nerve at different frequencies. Methyl-atropine (2 mg/kg i.v.) greatly attenuated, and bilateral cervical vagotomy completely elimin ated, phenylephrine-induced reflex bradycardia, whereas propranolol(1 mg/kg i.v.) caused a moderate decrease in the reflex bradycardic respo nse. Ethanol (1 g/kg i.v) did not influence the residual reflex bradyc ardia after methyl-atropine, but significantly decreased the residual reflex bradycardia after propranolol. Aortic nerve stimulation caused frequency-dependent hypotension, which was unaffected by methyl-atropi ne, and bradycardia, which was eliminated by methyl-atropine. Depletio n of endogenous GABA by pretreatment of rats with 3-mercaptopropionate slightly increased the bradycardic response to aortic nerve stimulati on and eliminated its susceptibility to inhibition by ethanol. Acute a ortic nerve denervation moderately reduced the reflex bradycardic resp onse to phenylephrine, which was no longer sensitive to inhibition by ethanol. These findings suggest that 1) ethanol inhibits baroreflex br adycardia but not hypotension, 2) the effect of ethanol is selective r egarding both the afferent (aortic vs. carotid baroreceptors) and effe rent limbs of the reflex (vagal vs, sympathetic) and 3) the effect of ethanol is mediated through endogenous GABA, probably at the level of the dorsal brainstem.