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 me diated by endothelin ETA and ETB receptors in human myocardial trabeculae f rom 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 cont ractile force upon exposure to agonist were studied. Endothelin-1 (ET-1) an d ET-3 had a strong positive inotropic effect in all trabeculae. ET-1 was s ignificantly more potent than ET-3 in both atrial (P < 0.001) and ventricul ar (P < 0.05) trabeculae. Preincubation with the ETA receptor antagonist FR 139317 (1 mu M) 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 ETB receptor agonist I RL 1620 had a positive inotropic effect only in some trabeculae, and the ET B receptor antagonist BQ 788 (1 mu M) almost completely blocked this effect . These results suggest that both ETA and ETB receptors mediate positive in otropic responses at both the atrial and ventricular level in the human hea rt.