Inhibition of baroreflex bradycardia by ethanol involves both GABAA and GABAB receptors in the brainstem of the rat.
The effects of ethanol on baroreceptor reflex bradycardia and its interactions with cardiovascular effects mediated by GABA receptors in the dorsal vagal complex were studied in urethane-anaesthetised rats. Ethanol, 1 g kg-1 administered i.v. or 25-200 nmol microinjected bilaterally into the dorsal vagal complex, inhibited the reflex bradycardic response to bolus i.v. doses of phenylephrine both in spontaneously breathing and in paralysed, artificially ventilated animals, and this effect could be prevented by pretreatment with the GABA-depleting agent, 3-mercaptopropionate in both groups of rats. Ethanol, 1 g kg-1 i.v., did not influence the bradycardic response to electrical stimulation of the cervical vagus. Microinjection of muscimol into the dorsal vagal complex caused a dose-dependent pressor response and inhibited baroreflex bradycardia. The pressor response was potentiated and a tachycardic response to muscimol emerged following microinjection of ethanol into the dorsal vagal complex. Similar administration of baclofen caused dose-dependent increases in blood pressure and heart rate and inhibited baroreflex bradycardia. Injection of ethanol into the dorsal vagal complex potentiated the pressor response to a low dose of baclofen but did not affect the tachycardic response. Bicuculline, 10 pmol/side into the dorsal vagal complex, blocked the effects of muscimol but not those of baclofen and reduced the baroreflex inhibitory action of ethanol. 2-Hydroxysaclofen, microinjected at 400 pmol to 1 nmol/side, blocked the effects of baclofen but not those of muscimol. 2-Hydroxysaclofen or phaclofen, 2 mg kg-1 s.c., prevented the baroreflex inhibitory action of ethanol and also prevented ethanol potentiation of the pressor and, less effectively, the tachycardic effects of muscimol. It is concluded that ethanol inhibits baroreflex bradycardia through potentiation of the actions of endogenous GABA in the dorsal vagal complex. Both GABAA and GABAB receptors appear to be involved in this action of ethanol.
Varga
K
K
Laboratory of Physiologic and Pharmacologic Studies, NIAAA, NIH, Bethesda, MD 20892.
Kunos
G
G
D015097:3-Mercaptopropionic Acid / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001919:Bradycardia / Q000503:physiopathology / Q000517:prevention & control*; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D011311:Pressoreceptors / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology
D011963:Receptors, GABA-A; D000431:Ethanol; D015097:3-Mercaptopropionic Acid; D001418:Baclofen; C057491:2-hydroxysaclofen