Reductions in blood pressure, heart rate and renal sympathetic nervous discharge after imidazole-4-acetic acid: mediation through central gamma-aminobutyric acid (GABA) receptor stimulation.

Intracerebroventricular administration of imidazole-4-acetic acid (IAA) (0.3--10 microgram/kg) significantly reduced mean arterial pressure, heart rate and renal sympathetic nerve discharge in chloralose-anesthetized cats. In contrast, i.v. administration of IAA did not lower arterial pressure or heart rate. This would suggest that the hypotensive and bradycardic effects of IAA were centrally mediated. The cardiovascular effects of IAA were attenuated by the central administration of bicuculline methiodide (15 microgram/kg), a gamma-aminobutyric acid receptor antagonist. Reflex bradycardia evoked during the pressor response to norepinephrine (0.03--1.0 microgram/kg i.v.) was reversed to tachycardia after only the central administration of IAA. The vasoconstrictor response evoked during a 20-sec period of bilateral occlusion of carotid arteries was not altered by IAA. These results suggest that the cardiovascular effects of IAA are mediated through the activation of central gamma-aminobutyric acid receptors, to inhibit sympathetic vasomotor outflow.