Reductions in blood pressure, heart rate and renal sympathetic nerve discharge in cats after the central administration of muscimol, a GABA agonist

Abstract

Muscimol, a central GABA receptor agonist, caused dose-related reductions in blood pressure and heart rate when administered intracerebroventricularly (i.c.v.) to anaesthetized cats (0.1–1.0 μg/kg). Renal sympathetic nerve discharge (RSND) was also inhibited at 0.3 and 1.0 μg/kg (i.c.v.). No effects were observed after the intravenous administration of muscimol. Bicuculline, a GABA receptor antagonist, completely reversed the effects of muscimol on blood pressure, heart rate and RSND, the most consistent, rapid and dramatic effects being observed after intravenous rather than intracerebroventricular administration. Pictrotoxin also reversed the effects of muscimol but the results were more variable than after bicuculline. Strychnine, a glycine receptor antagonist, and physostigmine, an acetylcholinesterase inhibitor, had no significant effects on the inhibition caused by muscimol. Muscimol was even more effective in baroreceptor denervated cats, than in non-denervated cats, probably as a result of the loss of compensatory reflex mechanisms. It is concluded that central stimulation of GABA receptors by muscimol results in marked reductions in blood pressure, heart rate and RSND which are specifically antagonized by GABA receptor antagonists.