Prostanoid-mediated inotropic responses are attenuated in failing human and rat ventricular myocardium.
Eur J Pharmacol
; 686(1-3): 66-73, 2012 Jul 05.
Article
en En
| MEDLINE
| ID: mdl-22546232
ABSTRACT
Prostanoid-modulatory approaches in heart failure patients have displayed effects which may seem to be mutually incompatible. Both treatment with prostanoids and inhibition of prostanoid synthesis have resulted in increased mortality in heart failure patients. Currently, it is unknown if prostanoids mediate contractile effects in failing human heart and if this can explain some of the clinical effects seen after prostanoid modulatory treatments. Therefore, the objectives of this study were to determine if prostanoids could elicit direct inotropic responses in human ventricle, and if so to determine if they are modified in failing ventricle. Contractile force was measured in left ventricular strips from non-failing or failing human and rat hearts. The ratio of phosphorylated to non-phosphorylated myosin light chain 2 (MLC-2) was measured by Western blotting in myocardial strips, and the levels of prostanoid FP receptor mRNA and protein were measured in rat by real-time RT-PCR and receptor binding assays. In non-failing human hearts, prostanoids evoked a positive inotropic effect and an increase of MLC-2 phosphorylation which was absent in failing human hearts. In failing rat heart, the prostanoid FP receptor-mediated inotropic response and prostanoid FP receptor-density was reduced by ~40-50% compared to non-failing rat heart. Prostanoids mediate a sustained positive inotropic response in non-failing heart, which appears to be down regulated in failing heart. The pathophysiological significance of changes in prostanoid-mediated inotropic support in the failing heart remains to be determined.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Prostaglandinas F Sintéticas
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Receptores de Prostaglandina
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Alprostadil
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Iloprost
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Insuficiencia Cardíaca
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Ventrículos Cardíacos
Límite:
Adolescent
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Adult
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Aged
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Aged80
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Animals
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Noruega