Modulation of contractile force by endothelin receptors in porcine myocardial trabeculae

The aim of the study was to determine possible inotropic effects mediated b y endothelin-A and endothelin-B receptors in porcine myocardial trabeculae from right atria and left ventricles. Isolated trabeculae were paced at 1.5 Hz in tissue baths, and changes in isometric contractile force upon exposu re to agonist were studied. Endothelin-l and endothelin-3 had a strong and potent positive inotropic effect in all trabeculae. In all atrial and in so me ventricular trabeculae this effect was preceded by a transient negative inotropic effect at 10(-7) M. The endothelin-B receptor agonist IRL 1620 ha d a positive inotropic effect in some of the ventricular trabeculae, and no negative inotropic effect. Another endothelin-B receptor agonist, sarafoto xin S6c, had no positive inotropic effect, but induced a transient negative inotropic effect in some atrial trabeculae at 10(-7) M. In atrial trabecul ae the preincubation with the endothelin-A receptor antagonist FR139317 (10 (-6) M) decreased significantly (P<0.01) the maximum positive inotropic res ponses and abolished negative inotropic responses to endothelin-l. In concl usion, both endothelin-A and endothelin-B receptors may have the potential to mediate both positive and negative inotropic responses, but a positive i notropic effect mediated mainly via endothelin-A receptors seems to predomi nate.