Cardiovascular effects of 3-mercaptopropionic acid and levels of GABA in regions of the brain of guinea-pigs

3-Mercaptopropionic acid (3-MP), an inhibitor of the synthesis of gamma-aminobutyric acid (GABA), was administered to anesthetized rats and guinea-pigs in order to examine the relationship between the effect of this agent on regional levels of GABA in the brain and cardiovascular function. After a latent period, 3-mercaptopropionic acid (0.16 ml/kg, i.p.) produced initial increases in blood pressure and heart rate in rats followed by vagal bradycardia and hypotension. Guinea-pigs treated with 3-mercaptopropionic acid developed one of three patterns of cardiovascular changes. The type I response consisted of a period of sympathetically-mediated hypertension and tachycardia followed by vagal bradycardia. Type II Animals exhibited increased arterial pressure and heart rate, but no vagal activation. Type III and control Animals exhibited no significant cardiovascular changes following administration of 3-mercaptopropionic acid or appropriate vehicle. Regional levels of GABA in brain, measured at 90 min after treatment were significantly lower than control in type I and II Animals in 3 of 4 areas of the brain measured, but not in type III guinea-pigs. When decreases in levels of GABA were compared to the changes in cardiovascular parameters for individual Animals, the decrease in heart rate at the time of sacrifice was directly correlated with the decrease in medullary levels of GABA in type I Animals. Conversely, in type II guinea-pigs, decreases in hypothalamic levels of GABA correlated inversely with heart rate at sacrifice. These results suggest that activation of cardiac sympathetic and parasympathetic nervous pathways following the administration of 3-mercaptopropionic acid may result from decreased levels of GABA in different regions of the brain.