Effects of 8-S-benzyl cyclic AMP on mechanical characteristic and cyclic AMP levels of the canine ventricular myocardium

Abstract

Effects of 8-S-benzyl cyclic AMP on the mechanical characteristics of cardiac contradiction and on teh intracellular cyclic AMP level were studied on the isolated canine right ventricular myocardium. For comparison, inotropic effects of dibutyryl and 8-bromo cyclic AMP were also investigated. 8-S-Benzyl cyclic AMP caused a concentration-dependent positive intropic action. The action of 8-S-benzyl cyclic AMP developed and reached a steady level much faster thant hat of dibutyryl cyclic AMP (dbcAMP), while the time courses of the disappearance of the actions following washout of the compounds did not differ. The dose-response curve for 8-S-benzyl cyclic AMP lay substantially in the same concentration range as did that for dbcAMP. The duration of a single contraction was decreased by 8-S-benzyl cyclic AMP in a concentration-dependent manner, chiefly because of shortening of the relaxation time. The cyclic AMP phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methylxanthine (IBMX) enhanced the positive inotropic action of 8-S-benzyl cyclic AMP; 8-bromo cyclic AMP caused a definite positive inotropic action only in the presence of IBMX. The intracellular cyclic AMP levels determined 5, 15 and 30 min after the administration of 1 mM 8-S-benzyl cyclic AMP were not significantly different from the corresponding control values determined in the paired muscle. The present results indicte that the changes in mechanical characteristics caused by 8-S-benzyl cyclic AMP were very similar to those induced by β-aderenoceptor stimulation. Since the intracellular cyclic AMP level was not changed after administration of 8-S-benzyl cyclic AMP, this compound is probably not metabolized intracellularly to cyclic AMP but acts directly as the original compound on the protein kinase. This compound provides an excellent pharmacological tool to mimic the effect of β-adrenoceptor stimulation on myocardial contractility.