Effect of muscimol on cholinomimetic-induced cardiovascular responses in rats

Brain acetylcholine and gamma-aminobutyric acid (GABA) are both involved in the regulation of central cardiovascular control. Despite data from anatom ical and electrophysiological experiments characterizing the interaction be tween central GABAergic and cholinergic neurotransmission, the potential si gnificance of this interaction in central cardiovascular regulation remains unknown. The purpose of this study was to determine whether activation of GABA(A) receptors by intracerebroventricular or intrahypothalamic administr ation of muscimol affects the cholinergic agonist-induced cardiovascullar r esponses. All experiments were performed in conscious, Sprague-Dawley rats instrumented with a guide cannula for drug injection and iliac arterial cat heters for direct measurement of mean arterial pressure and heart rate. Adm inistration of a cholinergic agonist, carbachol, either intracerebroventric ularly or into the dorsomedial hypothalamic nucleus, produced a significant increase in mean arterial pressure, whereas injection of carbachol into th e posterior hypothalamic nucleus caused a slight elevation in blood pressur e. Pretreatment with muscimol 10 min before administration of carbachol pre vented the carbachol-evoked blood pressure changes. On the other hand, carb achol produced variable changes in heart rate, depending on the site of inj ection. In [H-3]quinuclydinyl benzilate binding experiments, muscimol did n ot displace the muscarinic radioligand from its binding sites, suggesting t hat it does not exert any direct antagonistic activity at muscarinic recept ors. These results suggest that the dorsomedial hypothalamic nucleus is a p otential site of action for microinjected carbachol and that the GABAergic system has an inhibitory influence on cholinergic neurons involved in blood pressure regulation. (C) 1998 Elsevier Science B.V. All rights reserved.