Aldosterone increases NHE-1 expression and induces NHE-1-dependent hypertrophy in neonatal rat ventricular myocytes

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.