Possible inhibitory role of endogenous gamma-aminobutyric acid in the nonnicotinic functions of the dog cardiac sympathetic ganglia.

Participation of endogenous gamma-aminobutyric acid (GABA) in the functions of dog cardiac ganglia was investigated. The ganglionic stimulants as well as agents affecting GABA system were given directly into the cardiac sympathetic ganglia through the right subclavian artery (i.a.), unless otherwise mentioned. Inhibition of endogenous GABA degradation by the GABA-transaminase inhibitor, aminooxyacetic acid (AOAA) administered 10 mg/kg i.v. 2 hr before completion of surgical procedures did not alter the positive chronotropic responses to bethanecol (25 and 50 micrograms) and acetylcholine (25, 50 and 100 micrograms) but reduced markedly those to angiotensin II (1 and 2 micrograms). This reduction was antagonized by picrotoxin (5 mg). Diazepam given 10 mg/kg i.v. also inhibited the ganglionic responses to angiotensin II in both untreated and AOAA-pretreated dogs, this inhibition by diazepam being more marked in the AOAA-pretreated than in the untreated dogs. The same dose of diazepam did not affect the responses to acetylcholine but reduced to a certain degree of responses to bethanechol in the AOAA-pretreated dogs. These inhibitions by diazepam were also reversed by picrotoxin. After i.v. treatment with the glutamic acid decarboxylase inhibitors, 3-mercaptopropionic acid (50 mg/kg) or isoniazid (200 mg/kg), the ganglionic responses to angiotensin II were not altered, but inhibitory effects of diazepam on the responses to angiotensin II were eliminated after 3-mercaptopropionic acid but not after isoniazid. These results suggest that endogenous GABA may play an inhibitory role in the nonnicotinic ganglionic pathways and that diazepam probably exerts a ganglionic action through endogenous GABAergic mechanisms.