Hypotensive and postural effects of the gamma-aminobutyric acid agonist muscimol and of clonidine.

gamma-Aminobutyric acid (GABA) and GABA agonists, e.g., muscimol, have been shown to reduce blood pressure by a centrally mediated mechanism. The present series of experiments compared cardiovascular responses to muscimol with those of clonidine in anesthetized and conscious spontaneously hypertensive rats. Both agents given intraventricularly reduced blood pressure, heart rate, and spontaneous sympathetic outflow in anesthetized animals. Muscimol also produced marked hypotension in conscious rats. However, compensatory adjustments to upright tilt were inhibited only slightly at most by both agents, even at high doses. Therefore, muscimol, like other centrally acting hypotensive agents, appears to inhibit the sympathetic nervous system selectively.