The role of the sympathetic nervous system in the cardiovascular effects of systemically administered gamma-aminobutyric acid.
The role of the sympathetic nervous system in the circulatory effects of peripherally administered GABA was investigated in anesthetized dogs. Systemic administration of GABA (10-300 micrograms/kg) decreased blood pressure (BP) by 9-29 mmHg and heart rate (HR) by 15-60 beats/min in anesthetized dogs. Pretreatment with reserpine (1 mg/kg, i.m.) or ganglionic blockade with hexamethonium (10 mg/kg, i.v.) plus atropine (1 mg/kg, i.v.) abolished the GABA-induced hypotension and bradycardia. Intravertebral administration of GABA did not cause greater reduction in BP than by the i.v. route. Bicuculline (1 mg/kg, i.v.) attenuated the BP and HR responses to either intravertebrally or intravenously administered GABA, suggesting peripheral GABA receptors mediate the vasodepressor response to GABA. GABA prevented the bradycardia caused by the preganglionic vagal stimulation, suggesting GABA impairs ganglionic transmission. The depressant effect of GABA on ganglionic transmission was reversed by bicuculline. The depressor and bradycardic effects of i.v. GABA were not mediated by the release of either histamine or prostaglandins, since mepyramine or indomethacin pretreatment failed to alter the BP and HR responses to GABA. Since the doses of GABA used in this investigation probably do not pass the blood brain barrier, it is suggested that systemic administration of GABA decreases BP by a peripheral mechanism that is dependent upon an intact sympathetic nervous system and the ganglionic blocking activity of GABA most likely contributes to its vasodepressor effects upon systemic administration.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D011738:Pyrilamine / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014630:Vagus Nerve / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D005730:Ganglionic Blockers; D005680:gamma-Aminobutyric Acid; D012110:Reserpine; D011738:Pyrilamine; D007213:Indomethacin