Involvement of Cyclic AMP in the Positive Inotropic Effect of OPC-8212, a New Cardiotonic Agent, on the Canine Ventricular Muscle

OPC-8212 is a new positive inotropic drug which scarcely produces an increase in heart rate and vasodilatation. The positive inotropic effect of OPC-821 2 was investigated in relation to cyclic AMP metabolism in canine isolated ventricular muscle. The positive inotropic effect of OPC-8212 was accompanied by accumulation of cyclic AMP in the tissue: the cyclic AMP level was elevated before the increase in force of contraction and elevated in a concentration-dependent manner in the presence of a β-adrenoceptor antagonist, atenolol (10-6 M). The OPC-821 2-induced increases in force of contraction and cyclic AMP level were abolished by carbachol (3x10-6 M). The relationship between the force of contraction and cyclic AMP level in the presence of OPC-821 2 was changed by neither carbachol nor isoproterenol. OPC-8212 enhanced the positive inotropic effect of isoproterenol as cyclic AMP phosphodiesterase inhibitors did. OPC-8212 shortened the time to peak tension and had a tendency to shorten the relaxation time of single contractions. These results altogether suggest that change in cyclic AMP metabolism is involved at least in the positive inotropic effect of OPC-8212 on canine ventricular muscle.