THE ROLE OF BRAIN ACETYLCHOLINE IN GABA(A) RECEPTOR ANTAGONIST-INDUCED BLOOD-PRESSURE CHANGES IN RAT

Previous experimental studies have shown that intracerebroventricular (i.c.v.) injection of the GABA, receptor antagonist, bicuculline methi odide, results in marked increases in blood pressure due to an increas e in sympathetic nervous system activity. It is well recognized that t he central cholinergic system is also involved in the regulation of bl ood pressure. In the present study, we examined the role of brain acet ylcholine in the presser response induced by bicuculline methiodide in conscious Sprague-Dawley rats. I.c.v. (0.05, 0.3 and 0.5 nmol) and in trahypothalamic (40 pmol) administration of bicuculline methiodide pro duced blood pressure increases in a dose-dependent manner. Hemicholini um-3 was given i.c.v. 1 h prior to bicuculline methiodide. The depleti on of brain acetylcholine was demonstrated by the suppression of physo stigmine-induced presser responses, but blood pressure increases in re sponse to carbachol remained unchanged. The presser responses to bicuc ulline methiodide in animals pre-treated with hemicholinium-3 were sig nificantly higher than those seen in saline-pre-treated groups. Likewi se, bicuculline methiodide, at a dose that did not alter blood pressur e alone, caused presser responses in rats pre-treated with the nicotin ic receptor antagonist, mecamylamine, whereas the muscarinic receptor antagonist, atropine, was ineffective in this respect. In conclusion, it seems likely that endogenous brain acetylcholine has a modulator ro le on GABA, receptor-mediated blood-pressure control via nicotinic rec eptors.