In vivo and in vitro assessment of the cardiovascular effects of 8-(benzylthio)-N6-n-butyl-cyclic AMP.

In the canine heart-lung preparation (HLP) and the anesthetized open-chest dog, both 8-(Benzylthio)-N6-n-butyl-cyclic AMP (BTB-cyclic AMP) (10 times more potent) and dibutyryl-cyclic AMP (DB-cyclic AMP) produced a definite positive inotropic effect (PIE) and an increase in the coronary blood flow with either no change (HLP) or a slight increase (anesthetized animal) (BTB-cyclic AMP) and a definite increase in the heart rate (DB-cyclic AMP). In the isolated atrial preparations of the guinea pig (AG), BTB-cyclic AMP produced a slight PIE at 3 X 10(-5) M and a negative chronotropic effect at 3 X 10(-4) M. Aminophylline reversed the latter to the positive one, while potentiating the former. At 10(-3) M marked positive inotropic and chronotropic effects were observed. DB-cyclic AMP was without effects. In the right ventricular papillary muscle preparations of the guinea pig (PMG), both compounds produced PIE. BTB-cyclic AMP initiated a contraction (AG) and a "slow" action potential (PMG) in partially depolarized preparations. Both of these effects were abolished by diltiazem. BTB-cyclic AMP (10(-3) M) suppressed the heart rate increase induced by isoproterenol in right AG. It was concluded that BTB-cyclic AMP was a cardiotonic agent with a relatively weak positive chronotropic effect and that the cardiotonic effect was ascribable to the initiation of slow action potentials and related contractions.