Positive inotropic responses mediated by endothelin ETA and ETB receptors in human myocardial trabeculae

The aim of the present study was to determine possible inotropic effects mediated by endothelin ET_A and ET_B receptors in human myocardial trabeculae from the right atrium and the left ventricle. Isolated trabeculae from human hearts were paced at 1.0 Hz in tissue baths, and changes in isometric contractile force upon exposure to agonist were studied. Endothelin-1 (ET-1) and ET-3 had a strong positive inotropic effect in all trabeculae. ET-1 was significantly more potent than ET-3 in both atrial (P < 0.001) and ventricular (P < 0.05) trabeculae. Preincubation with the ET_A receptor antagonist FR139317 (1 μM) decreased significantly (P < 0.005) the potency of ET-1 in both atrial and ventricular trabeculae, without any significant changes in E_max (maximum effect obtained with an agonist). The ET_B receptor agonist IRL 1620 had a positive inotropic effect only in some trabeculae, and the ET_B receptor antagonist BQ 788 (1 μM) almost completely blocked this effect. These results suggest that both ET_A and ET_B receptors mediate positive inotropic responses at both the atrial and ventricular level in the human heart.