Effects of prostaglandin E1 on the positive inotropic actions of noradrenaline, nerve stimulation and calcium in the isolated blood-perfused papillary muscle of the dog.

The effects of PGE1 on the dog heart were studied using the blood-perfused sinus node and papillary muscle preparations isolated separately from the same animal. PGE1 administered into the papillary muscle artery as bolus injections in doses of 1-1000 ng caused a dose-dependent increase of the developed tension and dT/dt of the papillary muscle. The effect was not inhibited by the beta-adrenoceptor blocking agent pindolol. PGE1 injected into the sinus node artery in doses of 3-300 ng did not change the rate of contraction of the sinus node preparation. PGE1 in the blood concentrations of 4.4 X 10(-9) to 1.7 X 10(-7) M enhanced the positive inotropic responses to noradrenalin and field stimulation as well as to calcium. The influence of PGE1 on the positive inotropic effect of perivascular nerve stimulation was not consistent: the action of perivascular nerve stimulation was enhanced by PGE1 in the majority of preparations but was reduced in one third of preparations. PGE1 in the same blood concentrations as used in the papillary muscle significantly depressed the positive chronotropic responses to noradrenaline and dopamine. The present results indicate that PGE1 induces multiple actions on the dog heart. Its predominant effect on the ventricular myocardium appears to be enhancement of the adrenergic stimuli probably via the facilitation of calcium movement through the myocardial cell membrane. In addition, PGE1 may decrease the sensitivity of beta-adrenoceptors to adrenergic stimuli in the sinus node.