en
Scientific article
English

Corticosteroids and redox potential modulate spontaneous contractions in isolated rat ventricular cardiomyocytes

Published inHypertension, vol. 52, no. 4, p. 721-728
Publication date2008
Abstract

The mineralocorticoid receptor has been implicated in the development of several cardiac pathologies and could participate in the high incidence of lethal ventricular arrhythmias associated with hyperaldosteronism. We have observed previously that aldosterone markedly increases in vitro the rate of spontaneous contractions of isolated neonate rat ventricular myocytes, a putative proarrhythmogenic condition if occurring in vivo. In the present study, we investigated the effect of glucocorticoids, the involvement of the glucocorticoid receptor, and the modulation of their action by redox agents. Aldosterone and glucocorticoids exerted in vitro a similar, concentration-dependent chronotropic action on cardiomyocytes, which was mediated by both the mineralocorticoid and glucocorticoid receptors. However, the relative contribution of each receptor was different for each agonist, at each concentration. Angiotensin II induced a similar response that was entirely dependent on the activity of the glucocorticoid receptor. Corticosteroid action was modulated by the redox state of the cells, with oxidation increasing the response while reducing conditions partially preventing it. When only the mineralocorticoid receptor was functionally present in the cells, oxidation was necessary to reveal glucocorticoid action, but no obvious competition with mineralocorticoids was observed when both agonists where simultaneously present. In conclusion, corticosteroids exert a strong chronotropic action in ventricular cardiomyocytes, mediated by both the mineralocorticoid and glucocorticoid receptors and modulated by the redox state of the cell. This phenomenon is believed to be because of cell electric remodeling and could contribute in vivo to the deleterious consequence of inappropriate receptor activation, leading to increased susceptibility of patients to arrhythmias.

Keywords
  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Disease Models, Animal
  • Glucocorticoids/pharmacology
  • Heart Ventricles/cytology
  • Myocardial Contraction/drug effects/physiology
  • Myocytes, Cardiac/drug effects/metabolism/pathology/physiology
  • Oxidation-Reduction
  • Rats
  • Rats, Wistar
  • Receptors, Glucocorticoid/metabolism
  • Ventricular Function
Citation (ISO format)
ROSSIER, Michel et al. Corticosteroids and redox potential modulate spontaneous contractions in isolated rat ventricular cardiomyocytes. In: Hypertension, 2008, vol. 52, n° 4, p. 721–728. doi: 10.1161/HYPERTENSIONAHA.108.114223
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Article (Accepted version)
accessLevelRestricted
Identifiers
ISSN of the journal1524-4563
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