Antagonism by gamma-aminobutyric acid of the stimulant effect of angiotensin II on cardiac sympathetic ganglia in spinal dogs

Abstract

The effects of angiotensin II and neuro-aminoacids administered through the right subclavian artery (i.a.) to the cardiac sympathetic ganglia were investigated in spinal dogs. Angiotensin II (1--8 micrograms) elicited a dose-dependent positive chronotropic effect which was reduced after i.a. injection of saralasin (100 micrograms). The effect of angiotensin II was not reduced after combined treatment with either hexamethonium (10 mg/kg) plus atropine (0.1 mg/kg) or hemicholinium-3 (5 mg/kg) plus preganglionic stimulation. The dose-dependent response to angiotensin II of heart rate was inhibited by GABA (50, 500 micrograms), GABOB (500 micrograms) and muscimol (50, 100 micrograms). The inhibition of the response to angiotensin II by a small dose of GABA (50 micrograms), but not by a high one (500 micrograms), was antagonized by i.a. injection of picrotoxin (2 mg). The positive chronotropism induced by bethanechol (25, 50 micrograms) and a small dose of acetylcholine (25 micrograms) were significantly inhibited by a high dose (500 micrograms) but not by a low dose (50 micrograms) of GABA. These results confirm that angiotensin II stimulates cardiac chronotropism by acting on the angiotensin II receptor located at the cardiac ganglia and show that this stimulant effect is antagonized by GABA.