Interaction between isoniazid and diverse vasodilators: role of decreased cerebral GABA.
OBJECTIVE
To determine if the interaction between isoniazid and hydralazine, consisting of increased hypotension accompanied by bradycardia, occurs with other vasodilators.


METHODS
Blood pressure and heart rate responses to a number of vasodilators were determined in rats under chloralose-urethane, pretreated or not with 250 mg/kg of isoniazid. The influence of this dose of isoniazid on GABA levels in the hypothalamus and pons-medulla was assessed in other groups of rats.


RESULTS
Increased hypotension and bradycardia following i.p. isoniazid were observed with dipyridamole, prazosin, pinacidil and hydralazine given i.v. Bradycardia without increased hypotension appeared with papaverine and verapamil, while increased hypotension with unchanged heart rate was observed with minoxidil and captopril. Isoniazid decreased GABA in the hypothalamus and pons-medulla.


CONCLUSIONS
At the high dose used, isoniazid interacts with various vasodilators, irrespective of their mechanism of action. The interaction could be due to the influence of the drug on GABA levels at cardiovascular regulatory sites.
de los Angeles Sánchez-Salvatori
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Department of Pharmacology, School of Medicine, National University of Mexico.
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology; D004357:Drug Synergism; D006146:Guanidines / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007538:Isoniazid / Q000494:pharmacology*; D008297:Male; D008914:Minoxidil / Q000494:pharmacology; D020110:Pinacidil; D011149:Pons / Q000187:drug effects / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D006146:Guanidines; D014665:Vasodilator Agents; D006830:Hydralazine; D005680:gamma-Aminobutyric Acid; D008914:Minoxidil; D004176:Dipyridamole; D020110:Pinacidil; D002216:Captopril; D007538:Isoniazid; D011224:Prazosin