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Cardiovascular Research 1998 38(2):451-462; doi:10.1016/S0008-6363(98)00007-8
© 1998 by European Society of Cardiology
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Copyright © 1998, European Society of Cardiology

Modifications of myocardial Na+,K+-ATPase isoforms and Na+/Ca2+ exchanger in aldosterone/salt-induced hypertension in guinea pigs

Juan Fernando Ramñrez-Gila,c, Pascal Trouvéc, Nathalie Mougenota, Alain Carayonb, Philippe Lechata and Danièle Charlemagnec,*

aLaboratoire de Pharmacologie Cardiovasculaire, Service de Pharmocologie, IFR Génétique et Physiopathologie Cardiovasculaire, Hôpital Pitié-Salpêtrière, 47 Bd de l'Hôpital, 75651 Paris Cedex 13, France
bService de Biochimie, Faculté de Médecine Pitié-Salpêtrière, IFR Génétique et Physiopathologie Cardiovasculaire, Hôpital Pitié-Salpêtrière, Faculté de Médecine Pitié-Salpêtrière, 91 Bd de l'Hôpital, 75013 Paris Cedex 13, France
cINSERM-U127, Biologie et Physiopathologie du coeur et des vaisseaux, IFR Circulation Lariboisière, Université D. Diderot, 41 Bd de la Chapelle, 75475 Paris Cedex 10, France

* Corresponding author. Tel.: +33 (1) 4285 8065; Fax: +33 (1) 4874 2315; E-mail: daniele.charlemagne@inserm.lrb.ap-hop-paris.fr

Objective: The aim of this study was to determine whether changes in cardiac Na+,K+-ATPase subunits and Na+/Ca2+ exchanger expression are regulated in aldosterone-salt hypertensive guinea pigs. Methods: Guinea pigs (GP) were unilaterally nephrectomized and randomized into three groups (aldosterone-salt; control-salt; control). After 90 days of treatment, echocardiographic M-mode assessment and right carotid arterial catheterization were performed in vivo, and plasma hormones and electrolytes were measured. mRNA and protein levels were studied by Northern and Western blot analysis. Results: Aldosterone-salt treatment induced, (1) arterial hypertension (+40%) and LV hypertrophy (+60%) without altering LV-fractional shortening, (2) an increase in plasma norepinephrine levels (+262%) and suppression of renin activity. Northern blot analysis showed the presence of the mRNA encoding the three {alpha} isoforms and the β1 subunit of Na+,K+-ATPase in GP myocardium. In the aldosterone-salt group, levels of {alpha}1 and β1 mRNAs were unchanged. {alpha}2 mRNA was increased in both ventricles, whereas {alpha}3 mRNA was increased in hypertrophied LV only. Furthermore, levels of the Na+/Ca2+ exchanger mRNA were decreased in both ventricles. At protein level, the two major transcripts ({alpha}1 and {alpha}2) were detected but {alpha}3 isoform was not. Parallel changes in protein and mRNA accumulation of {alpha}1 and {alpha}2 isoforms were observed in hypertrophied LV. Conclusion: These results show that {alpha}1 and {alpha}2 isoforms are expressed in GP heart and that they are independently regulated in aldosterone-salt hypertension. Like the {alpha}1 isoform in renal tissue, {alpha}2 isoform is the main target of aldosterone-salt. Reciprocal expression of the Na+/Ca2+ exchanger and Na+,K+-ATPase suggests an adaptational mechanism which maintains an appropriate sodium gradient and calcium concentration in hypertensive myocardium.

KEYWORDS Aldosterone; Na+,K+-ATPase; Na+/Ca2+ exchanger; Hypertension; Heart; Guinea pigs


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