Differential effects of amrinone on contractility and taurine influx in rat and guinea pig hearts.
Amrinone (5-amino-3,4'-bipyridin-6(IH)-one) is a non-glycoside, non-catecholamine, positive inotropic agent with an unknown mechanism of action. In the Langendorff-perfused isolated guinea pig heart, we found that amrinone produced a maximum increase in contractile force of 33% at a concentration of 10 micrograms/ml (10.7 x 10(-5) M), without change in heart rate. Maximum response occurred within 2 min of initiating perfusion, and increased contractility persisted for several minutes of drug-free washout. Amrinone neither alleviated nor aggravated spontaneous arrhythmias. At the time of maximum inotropic response, amrinone produced no change in cyclic AMP levels. In contrast to the guinea pig, the Langendorff-perfused isolated rat heart responded with a decreased contractility when perfused with amrinone. Furthermore, whereas amrinone stimulated the influx of taurine in guinea pig hearts, taurine influx remained unaltered in rat hearts. This is the first case of stimulated taurine influx not being associated with an increase in cAMP concentrations. In the guinea pig heart, amrinone increased markedly the half life of exchange of intracellular calcium. It has been suggested that amrinone is positively inotropic because of a direct action on the contractile proteins. On the basis of our observations, we think it more likely to be due to the alterations in calcium flux caused by amrinone.
D000631:Aminopyridines / Q000494:pharmacology*; D000676:Amrinone; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D013045:Species Specificity; D013654:Taurine / Q000378:metabolism*
D000631:Aminopyridines; D002316:Cardiotonic Agents; D013654:Taurine; D000242:Cyclic AMP; D000676:Amrinone; D002118:Calcium