Reversible inhibitory action of adenosine diphosphate ribose on isolated rat heart and rat heart in vivo

Cardiotropic effects of endogenous regulator of intracellular ionic balance adenosine diphosphate ribose (ADP-ribose) was studied on isolated rat heart using standard retrograde perfusion and on rat heart in vivo by means of implanted arterial catheters. Parameters registered were heart rate, pressure developed in left ventricle of isolated heart and blood pressure of rats in vivo. It was shown that ADP-ribose exerted cardiotropic action on isolated rat heart and that its effects did not depend on effects of its metabolite AMP. In concentrations 10-70 mu M ADP-ribose caused negative dose dependent chronotropic effect. Amplitude of contraction of isolated heart changed equivocally. in concentration 70 mu M ADP-ribose in 50% of cases produced biphasic action: negative inotropic effect was preceded by positive inotropic effect. in other cases this concentration exerted negative inotropic effect. In concentration 10 mu M only negative inotropic effect was observed. Contrary to ADP-ribose its metabolite AMP exerted only monophasic positive inotropic effect on isolated heart. The preparations studied differed in dynamics of cardiotropic action. In experiments in vivo ADP-ribose and AMP caused monophasic negative chronotropic and monophasic positive inotropic effects.