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-8212 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 beta-adrenoceptor antagonist, atenolol (10(-6) M). The OPC-8212-induced increases in force of contraction and cyclic AMP level were abolished by carbachol (3 X 10(-6) M). The relationship between the force of contraction and cyclic AMP level in the presence of OPC-8212 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.
D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D011719:Pyrazines; D011804:Quinolines / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013876:Thiophenes / Q000494:pharmacology
D002316:Cardiotonic Agents; D011719:Pyrazines; D011804:Quinolines; D013876:Thiophenes; D001262:Atenolol; C041667:vesnarinone; D002217:Carbachol; D000242:Cyclic AMP; D007545:Isoproterenol; C013693:sulfolane