In porcine myocardial trabeculae, endothelin-A receptors predominantly mediate positive inotropic effects, though both endothelin-A and -B receptors can mediate positive and negative inotropic responses.
Findings in porcine trabeculae warrant caution before clinical translation; extends receptor-specific inotropy insights in animal models.
The aim of the study was to determine possible inotropic effects mediated by 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 exposure to agonist were studied. Endothelin‐1 and endothelin‐3 had a strong and potent positive inotropic effect in all trabeculae. In all atrial and in some ventricular trabeculae this effect was preceded by a transient negative inotropic effect at 10 −7 M. The endothelin‐B receptor agonist IRL 1620 had a positive inotropic effect in some of the ventricular trabeculae, and no negative inotropic effect. Another endothelin‐B receptor agonist, sarafotoxin S6c, had no positive inotropic effect, but induced a transient negative inotropic effect in some atrial trabeculae at 10 −7 M. In atrial trabeculae the preincubation with the endothelin‐A receptor antagonist FR139317 (10 −6 M) decreased significantly (P<0.01) the maximum positive inotropic responses and abolished negative inotropic responses to endothelin‐1. In conclusion, both endothelin‐A and endothelin‐B receptors may have the potential to mediate both positive and negative inotropic responses, but a positive inotropic effect mediated mainly via endothelin‐A receptors seems to predominate.
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Opgaard et al. (2000) studied this question.
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