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(Hypertension. 2003;42:1171.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Aldosterone Increases NHE-1 Expression and Induces NHE-1-Dependent Hypertrophy in Neonatal Rat Ventricular Myocytes

Morris Karmazyn; Que Liu; Xiaohong Tracey Gan; Brenda J. Brix; Larry Fliegel

From the Department of Physiology and Pharmacology, University of Western Ontario (M.K., Q.L., X.T.G.), London, Ontario, and the Department of Biochemistry, University of Alberta (B.J.B., L.F.), Edmonton, Alberta, Canada.

Correspondence to Dr Morris Karmazyn, Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, N6A 5C1, Canada. E-mail morris.karmazyn{at}fmd.uwo.ca

We determined the effect of 24-hour aldosterone (100 nmol/L) treatment on hypertrophic responses in rat neonatal ventricular myocytes and the possible role of Na⁺-H⁺ exchange isoform 1 (NHE-1). Aldosterone significantly increased cell size by 61% and expression of atrial natriuretic peptide by 2-fold. NHE-1 mRNA expression and protein abundance were significantly increased, and intracellular Na⁺ levels were elevated. Both hypertrophy and elevated Na⁺ levels were prevented by the NHE-1-specific inhibitor EMD87580 as well as the aldosterone antagonist spironolactone, although the increased NHE-1 levels were prevented only by spironolactone. Aldosterone transiently (within 5 minutes) stimulated p44/42 phosphorylation, which decreased thereafter for the remaining 24 hours, whereas p38 phosphorylation was reduced. Neither a p38 nor a p44/42 inhibitor had any effect on aldosterone-induced hypertrophy or NHE-1 regulation. Our results therefore demonstrate a direct hypertrophic effect of aldosterone on cultured myocytes, which is dependent on NHE-1 activity.

Key Words: aldosterone • sodium-proton exchange • kinase • rats • hypertrophy, cardiac • myocytes

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