Basic research| Volume 27, ISSUE 6, P834-842, November 2011

Download started.


Metabolic Remodelling of Cardiac Myocytes During Pregnancy: The Role of Mineralocorticoids

Published:September 12, 2011DOI:



      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.


      We have applied rapid video imaging, echocardiography, patch clamp technique, confocal microscopy, and time-resolved fluorescence spectroscopy.


      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.


      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.



      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.


      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.


      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.


      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.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Canadian Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Holness M.J.
        • Liu Y.L.
        • Beech J.S.
        • Sugden M.C.
        Glucose utilization by interscapular brown adipose tissue in vivo during nutritional transitions in the rat.
        Biochem J. 1991; 273: 233-235
        • Bassien-Capsa V.
        • Fouron J.C.
        • Comte B.
        • Chorvatova A.
        Structural, functional and metabolic remodeling of rat left ventricular myocytes in normal and in sodium-supplemented pregnancy.
        Cardiovasc Res. 2006; 69: 423-431
        • Qin W.
        • Rudolph A.E.
        • Bond B.R.
        • et al.
        Transgenic model of aldosterone-driven cardiac hypertrophy and heart failure.
        Circ Res. 2003; 93: 69-76
        • Arriza J.L.
        • Weinberger C.
        • Cerelli G.
        • et al.
        Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor.
        Science. 1987; 237: 268-275
        • Nagata K.
        • Obata K.
        • Xu J.
        • et al.
        Mineralocorticoid receptor antagonism attenuates cardiac hypertrophy and failure in low-aldosterone hypertensive rats.
        Hypertension. 2006; 47: 656-664
        • Funder J.W.
        RALES, EPHESUS and redox.
        J Steroid Biochem Mol Biol. 2005; 93: 121-125
        • Sun Y.
        • Zhang J.
        • Lu L.
        • et al.
        Aldosterone-induced inflammation in the rat heart: role of oxidative stress.
        Am J Pathol. 2002; 161: 1773-1781
        • Beswick R.A.
        • Dorrance A.M.
        • Leite R.
        • Webb R.C.
        NADH/NADPH oxidase and enhanced superoxide production in the mineralocorticoid hypertensive rat.
        Hypertension. 2001; 38: 1107-1111
        • Liu G.
        • Grifman M.
        • Keily B.
        • et al.
        Mineralocorticoid receptor is involved in the regulation of genes responsible for hepatic glucose production.
        Biochem Biophys Res Commun. 2006; 342: 1291-1296
        • Zorzano A.
        • Herrera E.
        Effects of anesthetics and starvation on in vivo gluconeogenesis in virgin and pregnant rats.
        Metabolism. 1984; 33: 553-558
        • Pearce P.
        • Funder J.W.
        High affinity aldosterone binding sites (type I receptors) in rat heart.
        Clin Exp Pharmacol Physiol. 1987; 14: 859-866
        • Esumi K.
        • Nishida M.
        • Shaw D.
        • et al.
        NADH measurements in adult rat myocytes during simulated ischemia.
        Am J Physiol. 1991; 260: H1743-H1752
        • Goldhaber J.I.
        • Liu E.
        Excitation-contraction coupling in single guinea-pig ventricular myocytes exposed to hydrogen peroxide.
        J Physiol. 1994; 477: 135-147
        • Chorvat Jr, D.
        • Chorvatova A.
        Multi-wavelength fluorescence lifetime spectroscopy: a new approach to the study of endogenous fluorescence in living cells and tissues.
        Laser Phys Lett. 2009; 6: 175-193
        • Chorvat Jr, D.
        • Mateasik A.
        • Cheng Y.
        • et al.
        Rejection of transplanted hearts in patients evaluated by the component analysis of multi-wavelength NAD(P)H fluorescence lifetime spectroscopy.
        J Biophotonics. 2010; 3: 646-652
        • Bird D.K.
        • Yan L.
        • Vrotsos K.M.
        • et al.
        Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH.
        Cancer Res. 2005; 65: 8766-8773
        • Niesner R.
        • Peker B.
        • Schlusche P.
        • Gericke K.H.
        Noniterative biexponential fluorescence lifetime imaging in the investigation of cellular metabolism by means of NAD(P)H autofluorescence.
        Chemphyschem. 2004; 5: 1141-1149
        • Brouillette J.
        • Clark R.B.
        • Giles W.R.
        • Fiset C.
        Functional properties of K+ currents in adult mouse ventricular myocytes.
        J Physiol. 2004; 559: 777-798
        • Piquard F.
        • Schaefer A.
        • Dellenbach P.
        • Haberey P.
        Lactate movements in the term human placenta in situ.
        Biol Neonate. 1990; 58: 61-68
        • Alonso de la Torre S.R.
        • Serrano M.A.
        • Alvarado F.
        • Medina J.M.
        Carrier-mediated L-lactate transport in brush-border membrane vesicles from rat placenta during late gestation.
        Biochem J. 1991; 278: 535-541
        • Bergman B.C.
        • Tsvetkova T.
        • Lowes B.
        • Wolfel E.E.
        Myocardial glucose and lactate metabolism during rest and atrial pacing in humans.
        J Physiol. 2009; 587: 2087-2099
        • Mallet R.T.
        Pyruvate: metabolic protector of cardiac performance.
        Proc Soc Exp Biol Med. 2000; 223: 136-148
        • Rozanski G.J.
        • Xu Z.
        Glutathione and K(+) channel remodeling in postinfarction rat heart.
        Am J Physiol Heart Circ Physiol. 2002; 282: H2346-H2355
        • Tomaselli G.F.
        • Marban E.
        Electrophysiological remodeling in hypertrophy and heart failure.
        Cardiovasc Res. 1999; 42: 270-283
        • Eghbali M.
        • Deva R.
        • Alioua A.
        • et al.
        Molecular and functional signature of heart hypertrophy during pregnancy.
        Circ Res. 2005; 96: 1208-1216
        • Perrier E.
        • Kerfant B.G.
        • Lalevee N.
        • et al.
        Mineralocorticoid receptor antagonism prevents the electrical remodeling that precedes cellular hypertrophy after myocardial infarction.
        Circulation. 2004; 110: 776-783