Central antihypertensive properties of muscimol and related gamma-aminobutyric acid agonists and the interaction of muscimol with baroreceptor reflexes.
The central antihypertensive properties of four gamma-aminobutyric acid (GABA) analogs were characterized in anesthetized cats with implanted intracerebroventricular cannulae. An intracerebroventricular infusion (icv) of muscimol, 0.1--0.5 microgram/min (total dose: 1--5 micrograms, icv), substantially reduced mean arterial pressure and slightly reduced heart rate. The compound was not hypotensive at 5 micrograms, iv (total dose) and only slightly hypotensive after an intracisternal injection (5 micrograms). Kojic amine (2-aminomethyl-5-hydroxy-4H-pyran-4-one) and baclofen were also hypotensive following an intracerebroventricular infusion, but they were less active than muscimol. GABA, at 15--150 micrograms/min, icv (total dose, 150--1500 micrograms, icv), was not hypotensive by itself and unlike muscimol its activity was not enhanced in cats pretreated with nipecotic acid, an uptake inhibitor of GABA. The ability of muscimol to interfere with baroreceptor reflexes was considered in experiments in which reflex vasoconstrictor (carotid occlusion) and reflex vasodilatation (acute elevation in mean arterial pressure with norepinephrine) was measured in the perfused hindlimb of cats previously prepared with intracerebroventricular cannulae. Muscimol significantly attenuated the response to bilateral carotid occlusion and completely abolished reflex vasodilatation. The results suggest that GABA agonists and analogs may regulate blood pressure centrally and, through an interaction with the central nervous system, may attenuate baroreceptor reflexes.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D009118:Muscimol / Q000031:analogs & derivatives / Q000494:pharmacology*; D010080:Oxazoles / Q000494:pharmacology*; D011311:Pressoreceptors / Q000502:physiology*; D012018:Reflex; D014666:Vasomotor System / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology*
D010080:Oxazoles; D009118:Muscimol; D005680:gamma-Aminobutyric Acid