Modulation of contractile force by endothelin receptors in porcine myocardial trabeculae.
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.
Saetrum Opgaard
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Department of Pharmacology, Erasmus University, Rotterdam, The Netherlands. osaetrum@uci.edu
Tom
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de Vries
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Edvinsson
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Saxena
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PR
D000704:Analysis of Variance; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D017466:Receptors, Endothelin / Q000187:drug effects*; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014757:Viper Venoms / Q000494:pharmacology*
D001381:Azepines; D016232:Endothelins; D007211:Indoles; D010446:Peptide Fragments; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C074308:sovateltide; C079574:FR 139317