The influence of sympathomimetic amines, monoamine oxidase inhibitors, and antihypertensives upon the energy metabolism in the rat heart.

Abstract

This investigation was undertaken to determine the effects of three classes of catecholamine-releasing drugs on cardiac energy metabolism. The levels of adenosine monophosphate (AMP), adenosine diphosphate (ADP), adenosine triphosphate (ATP), inorganic phosphate (IP), and phosphocreatine (CP) of the rat heart were measured. The sympathomimetic amines tyramine, ephedrine, methylamphetamine, and (+)- and (−)-amphetamine caused significant decreases in CP. Tyramine and (+)- and (−)-amphetamine also significantly depressed ATP. Of the antihypertensive drugs investigated, bretylium and guanethidine decreased the amount of CP present, and the latter compound also significantly decreased ATP. The administration of reserpine was without significant effect on cardiac high-energy phosphate levels. Among the monoamine oxidase inhibitors, tranylcypromine significantly lowered ATP and CP, whereas pheniprazine produced no significant changes. This study showed that those drugs which have been reported to release cardiac catecholamines also reduced cardiac levels of CP and ATP. The hypothesis is advanced that this effect is due to increased utilization of energy by two mechanisms: (a) stimulation of the active recapture mechanism for adrenergic neurotransmitters, and (b) the positive inotropic and chronotropic responses of the heart to the drug-released catecholamines. In either case, the observed decreases in the levels of ATP and CP in the heart are effects of sympathomimetic amines which have been heretofore unreported.