The role of brain acetylcholine in GABA(A) receptor antagonist-induced blood-pressure changes in rat


Tellioglu T., Akin S., Ozkutlu U., Oktay S., Onat F.

EUROPEAN JOURNAL OF PHARMACOLOGY, vol.317, pp.301-307, 1996 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 317
  • Publication Date: 1996
  • Doi Number: 10.1016/s0014-2999(96)00744-3
  • Title of Journal : EUROPEAN JOURNAL OF PHARMACOLOGY
  • Page Numbers: pp.301-307

Abstract

Previous experimental studies have shown that intracerebroventricular (i.c.v.) injection of the GABA, receptor antagonist, bicuculline methiodide, results in marked increases in blood pressure due to an increase in sympathetic nervous system activity. It is well recognized that the central cholinergic system is also involved in the regulation of blood pressure. In the present study, we examined the role of brain acetylcholine 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 intrahypothalamic (40 pmol) administration of bicuculline methiodide produced blood pressure increases in a dose-dependent manner. Hemicholinium-3 was given i.c.v. 1 h prior to bicuculline methiodide. The depletion of brain acetylcholine was demonstrated by the suppression of physostigmine-induced presser responses, but blood pressure increases in response to carbachol remained unchanged. The presser responses to bicuculline methiodide in animals pre-treated with hemicholinium-3 were significantly higher than those seen in saline-pre-treated groups. Likewise, bicuculline methiodide, at a dose that did not alter blood pressure alone, caused presser responses in rats pre-treated with the nicotinic 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 role on GABA, receptor-mediated blood-pressure control via nicotinic receptors.