Inotropic effects of diadenosine tetraphosphate in isolated canine cardiacpreparations

We studied the effects of diadenosine tetraphosphate (AP(4)A) on the force of contraction in canine preparations. The force of contraction was measure d in isolated electrically driven (1 Hz) atrial and ventricular cardiac tra beculae from adult dogs. AP(4)A (100 mu M) alone and after prestimulation w ith 10 nM isoproterenol reduced force of contraction in atrial preparations by similar to 24%. Moreover, AP(4)A (100 mu M) alone and after prestimulat ion with 10 nM isoproterenol reduced the force of contraction in ventricula r preparations by 29 and 29%, respectively. The negative inotropic effects of AP(4)A were abolished by the A(1)-adenosine receptor antagonist 1,3-dipr opyl-cyclopentyl-xanthine (DPCPX). In summary, in canine myocardium, AP(4)A alone and after prestimulation with a beta-adrenoceptor agonist exerts neg ative inotropic effects, which are probably mediated via A(1)-adenosine rec eptors.