Inotropic effect of prostacyclin (PGI2) on isolated rat atria at different contraction frequencies

Abstract

The effects of a wide range of Prostacyclin (PGI₂) concentrations on the Isometric Developed Tension (IDT) of isolated left auricles driven at different frequencies (0.8, 1.6 or 3.3 Hz) were explored. A comparison of the positive inotropism of PGI₂, norepinephrine (NE), tyramine and phenylephrine (Phenyl) indicated that PGI₂, NE and tyramine enhanced peak tension significantly less at slow (0.8 and 1.6 Hz) than at higher rates (3.3 Hz); whereas Phenyl augmented equally the IDT at all of these three driving frequencies. The positive inotropism evoked by PGI₂ was inhibited by (−)-propranolol and also by a treatment with 6-OHDA. Cocaine, normetanephrine and U-0521, augmented the positive inotropic influence of PGI₂ on atria paced at a slow rate (0.8 Hz) but not at a faster one (3.3 Hz). These results suggest that the action of PGI₂ on atrial contractions is apparently indirect and mediated by the release of tissue catecholamines. In addition the effect of PGI₂ and NE at slow and fast rates appears associated with a different relative relevance of the processes which terminate the action of added sympathomimetic agonists, namely, neuronal or extraneuronal uptake as well as metabolization via COMT. These mechanisms seen to be more prominent at slower driving frequencies and could explain the diminished effect of PGI₂ and NE on slowly paced atria.