K. Varga et al., ENDOGENOUS GAMMA-AMINOBUTYRIC-ACID (GABA) MEDIATES ETHANOL INHIBITIONOF VAGALLY MEDIATED REFLEX BRADYCARDIA ELICITED FROM AORTIC BARORECEPTORS, The Journal of pharmacology and experimental therapeutics, 268(2), 1994, pp. 1057-1062
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.