Involvement of cyclic AMP in the positive inotropic effect of OPC-8212, a new cardiotonic agent, on the canine ventricular muscle.

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Abstract
OPC-8212 is a new positive inotropic drug which scarcely produces an increase in heart rate and vasodilation. This effect of OPC-8212 was investigated in relation to cAMP metabolism in canine isolated ventricular muscle. The positive inotropic effect of OPC-8212 was accompanied by accumulation of cAMP in the tissue: the cAMP level was elevated before the increase in force of contraction and elevated in a concentration-dependent manner in the presence of a .beta.-adrenoceptor antagonist, atenolol (10-6 M). The OPC-8212-induced increases in force of contraction and AMP level were abolished by carbachol (3 .times. 10-5 M). The relationship between the force of contraction and cAMP level in the presence of OPC-8212 was changed by neither carbachol nor isoproterenol. OPC-8212 enhanced the positive inotropic effect of isoproterenol as cAMP phosphodiesterase inhibitors did. OPC-8212 shortened the time to peak tension and had a tendency to shorten the relaxation time of single contractions. A change in cAMP metabolism is evidently involved at least in the positive inotropic effect of OPC-8212 on canine ventricular muscle.

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