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

Abstract

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.

• Authors: Morris Karmazyn, Que Liu, Xiaohong Tracey Gan, Brenda J Brix, Larry Fliegel
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 42 Issue 6 Pg. 1171-6 (Dec 2003) ISSN: 1524-4563 [Electronic] United States
• PMID: 14610099 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• RNA, Messenger
• Sodium-Hydrogen Exchangers
• growth factor-activatable Na-H exchanger NHE-1
• Aldosterone
• Sodium
• Mitogen-Activated Protein Kinases

Topics

• Aldosterone (pharmacology)
• Animals
• Animals, Newborn
• Cardiomegaly (etiology)
• Cell Size (drug effects)
• Cells, Cultured
• Enzyme Inhibitors (pharmacology)
• Gene Expression Regulation
• Heart Ventricles (cytology, growth & development)
• Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
• Myocytes, Cardiac (cytology, drug effects, metabolism)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Sodium (physiology)
• Sodium-Hydrogen Exchangers (biosynthesis, genetics, physiology)