INTERACTION BETWEEN ISONIAZID AND DIVERSE VASODILATORS - ROLE OF DECREASED CEREBRAL GABA

Objective: To determine if the interaction between isoniazid and hydra lazine, consisting of increased hypotension accompanied by bradycardia , occurs with other vasodilators. Methods: Blood pressure and heart ra te responses to a number of vasodilators were determined in rats under chloralose-urethane, pretreated or not with 250 mg/kg of isoniazid. T he influence of this dose of isoniazid on GABA levels in the hypothala mus and pons-medulla was assessed in other groups of rats. Results: In creased hypotension and bradycardia following i.p. isoniazid were obse rved with dipyridamole, prazosin, pinacidil and hydralazine given i.v. Bradycardia without increased hypotension appeared with papaverine an d verapamil, while increased hypotension with unchanged heart rate was observed with minoxidil and captopril. Isoniazid decreased GABA in th e hypothalamus and pons-medulla. Conclusions: At the high dose used, i soniazid interacts with various vasodilators, irrespective of their me chanism of action. The interaction could be due to the influence of th e drug on GABA levels at cardiovascular regulatory sites. (C) 1998 Els evier Science B.V.