Endogenous gamma-aminobutyric acid (GABA) mediates ethanol inhibition of vagally mediated reflex bradycardia elicited from aortic baroreceptors.
We have previously demonstrated that ethanol depresses baroreflex bradycardia by potentiating the similar action of endogenous gamma-aminobutyric acid (GABA) in the medullary dorsal vagal complex. In the present study we examined the relative contribution of the sympathetic vs. the parasympathetic nervous system and aortic vs. carotid sinus baroreceptors in this effect. Depressor baroreflex responses were elicited in urethane-anesthetized male Sprague-Dawley rats by i.v. injection of graded 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 eliminated, phenylephrine-induced reflex bradycardia, whereas propranolol (1 mg/kg i.v.) caused a moderate decrease in the reflex bradycardic response. Ethanol (1 g/kg i.v) did not influence the residual reflex bradycardia after methyl-atropine, but significantly decreased the residual reflex bradycardia after propranolol. Aortic nerve stimulation caused frequency-dependent hypotension, which was unaffected by methyl-atropine, and bradycardia, which was eliminated by methyl-atropine. Depletion of endogenous GABA by pretreatment of rats with 3-mercaptopropionate slightly increased the bradycardic response to aortic nerve stimulation and eliminated its susceptibility to inhibition by ethanol. Acute aortic nerve denervation moderately reduced the reflex bradycardic response to phenylephrine, which was no longer sensitive to inhibition by ethanol. These findings suggest that 1) ethanol inhibits baroreflex bradycardia but not hypotension, 2) the effect of ethanol is selective regarding both the afferent (aortic vs. carotid baroreceptors) and efferent 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.
Varga
K
K
Department of Pharmacology, Medical College of Virginia, Richmond.
Gantenberg
N S
NS
Kunos
G
G
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology; D011311:Pressoreceptors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D014630:Vagus Nerve / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000431:Ethanol; D005680:gamma-Aminobutyric Acid