Positive inotropic responses mediated by endothelin ET(A) and ET(B) 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 microM) decreased significantly (P < 0.005) the potency of ET- I in both atrial and ventricular trabeculae, without any significant changes in Emax (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 microM) 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.
Saetrum Opgaard
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Department of Pharmacology, Erasmus University Medical Centre EMCR, Rotterdam, The Netherlands. osaetrum@uci.edu
Möller
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de Vries
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Edvinsson
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Saxena
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PR
D000293:Adolescent; D000328:Adult; D016275:Atrial Function; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology; D019334:Endothelin-3 / Q000494:pharmacology; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists / Q000502:physiology*; D013268:Stimulation, Chemical; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D016276:Ventricular Function
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D019334:Endothelin-3; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D009638:Norepinephrine