The aim of the present study was to determine possible inotropic effects mediated by endothelin ETA and ETB 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 ETA receptor antagonist FR139317 (1 μM) decreased significantly (P < 0.005) the potency of ET-1 in both atrial and ventricular trabeculae, without any significant changes in Emax (maximum effect obtained with an agonist). The ETB receptor agonist IRL 1620 had a positive inotropic effect only in some trabeculae, and the ETB receptor antagonist BQ 788 (1 μM) almost completely blocked this effect. These results suggest that both ETA and ETB receptors mediate positive inotropic responses at both the atrial and ventricular level in the human heart.
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Research Article|
August 02 2000
Positive inotropic responses mediated by endothelin ETA and ETB receptors in human myocardial trabeculae
Ole SAETRUM OPGAARD;
*Department of Pharmacology, Erasmus University Medical Centre ‘EMCR’, Rotterdam, The Netherlands
†Division of Experimental Vascular Research, Department of Medicine, University Hospital, Lund, Sweden
Correspondence: Dr Ole Saetrum Opgaard, Department of Pharmacology, College of Medicine, 360 Med Surge II, University of California, Irvine, CA 92697-4625, U.S.A. (e-mail [email protected]).
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Sebastian MÖLLER;
Sebastian MÖLLER
†Division of Experimental Vascular Research, Department of Medicine, University Hospital, Lund, Sweden
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René DE VRIES;
René DE VRIES
*Department of Pharmacology, Erasmus University Medical Centre ‘EMCR’, Rotterdam, The Netherlands
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Lars EDVINSSON;
Lars EDVINSSON
†Division of Experimental Vascular Research, Department of Medicine, University Hospital, Lund, Sweden
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Pramod R. SAXENA
Pramod R. SAXENA
*Department of Pharmacology, Erasmus University Medical Centre ‘EMCR’, Rotterdam, The Netherlands
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Publisher: Portland Press Ltd
Received:
October 12 1999
Revision Received:
February 14 2000
Accepted:
April 12 2000
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2000
2000
Clin Sci (Lond) (2000) 99 (3): 161–168.
Article history
Received:
October 12 1999
Revision Received:
February 14 2000
Accepted:
April 12 2000
Citation
Ole SAETRUM OPGAARD, Sebastian MÖLLER, René DE VRIES, Lars EDVINSSON, Pramod R. SAXENA; Positive inotropic responses mediated by endothelin ETA and ETB receptors in human myocardial trabeculae. Clin Sci (Lond) 1 September 2000; 99 (3): 161–168. doi: https://doi.org/10.1042/cs0990161
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