Abstract
Background
Pregnancy is associated with significant cardiac adaptations. The regulatory mechanisms
involved in functional cardiac adaptations during pregnancy are still largely unknown.
In pathologic conditions, mineralocorticoids have been shown to mediate structural
as well as functional remodelling of the heart. However, their role in cardiac physiological
conditions is not completely understood. Here, we examined cardiac cell metabolic
remodelling in the late stages of rat pregnancy, as well as mineralocorticoid involvement
in this regulation.
Methods
We have applied rapid video imaging, echocardiography, patch clamp technique, confocal
microscopy, and time-resolved fluorescence spectroscopy.
Results
Our results revealed that cardiac cells undergo metabolic remodelling in pregnancy.
Inhibition of mineralocorticoid receptors during pregnancy elicited functional alterations
in cardiac cells: blood levels of energy substrates, particularly lactate, were decreased.
As a consequence, the cardiomyocyte contractile response to these substrates was blunted,
without modifications of L-type calcium current density. Interestingly, this response
was associated with changes in the mitochondrial metabolic state, which correlated
with modifications of bound reduced nicotinamide adenine dinucleotide (phosphate)
NAD(P)H levels. We also noted that mineralocorticoid receptor inhibition prevented
pregnancy-induced decrease in transient outward potassium current.
Conclusions
This study demonstrates that in pregnancy, mineralocorticoids contribute to functional
adaptations of cardiac myocytes. By regulating energy substrate levels, in particular
lactate, in the plasma and metabolic state in the cells, mineralocorticoids affect
the contractility responsiveness to these substrates. In the future, understanding
cardiac adaptations during pregnancy will help us to comprehend their pathophysiological
alterations.
Résumé
Introduction
La grossesse est associée à des adaptations cardiaques significatives. Les mécanismes
régulateurs impliqués dans les adaptations cardiaques fonctionnelles durant la grossesse
sont en grande partie encore inconnus. Au cours d'états pathologiques, il a été montré
que les minéralocorticoïdes servaient de médiateur aussi bien dans le remodelage structurel
que dans le remodelage fonctionnel du cœur. Cependant, leur rôle au cours d'états
physiologiques cardiaques n'est pas complètement compris. Ici, nous avons examiné
le remodelage métabolique de la cellule cardiaque dans les dernières étapes de la
grossesse chez la rate, aussi bien que l'implication du minéralocorticoïde dans cette
régulation.
Méthodes
Nous avons appliqué l'imagerie vidéo rapide, l'échocardiographie, la technique du
patch-clamp, la microscopie confocale et la spectroscopie de fluorescence résolue en temps.
Résultats
Nos résultats ont révélé que les cellules cardiaques subissent un remodelage métabolique
durant la grossesse. L'inhibition des récepteurs minéralocorticoïdes durant la grossesse
a provoqué des modifications fonctionnelles dans les cellules cardiaques : les niveaux
sanguins des substrats énergétiques, particulièrement le lactate, ont été diminués.
En conséquence, la réponse contractile des cardiomyocytes à ces substrats a été atténuée,
sans modifications de la densité du courant calcique de type L. De façon intéressante,
cette réponse a été associée aux changements de l'état métabolique des mitochondries,
lequel corrélait avec les modifications des niveaux de nicotinamide adénine dinucléotide
(phosphate) réduit NAD(P)H lié. Nous avons aussi noté que l'inhibition du récepteur
minéralocorticoïde prévenait la diminution induite par la grossesse dans le courant
potassique transitoire sortant.
Conclusions
Cette étude démontre que durant la grossesse, les minéralocorticoïdes contribuent
aux adaptations fonctionnelles des myocytes cardiaques. En régulant les niveaux de
substrats énergétiques, en particulier le lactate, dans le plasma et l'état métabolique
dans les cellules, les minéralocorticoïdes affectent la réponse contractile à ces
substrats. Dans le futur, la compréhension des adaptations cardiaques durant la grossesse
nous aidera à saisir les changements pathophysiologiques.
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Article info
Publication history
Published online: September 12, 2011
Accepted:
May 12,
2011
Received:
February 22,
2011
Footnotes
See page 841 for disclosure information.
Identification
Copyright
© 2011 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
