Regression of isoproterenol-induced cardiac hypertrophy by Na+/H+ exchanger inhibition

Irene L. Ennis, Eduardo M. Escudero, Gloria M. Console, Gisela Camihort, César Gomez Dumm, Randolph W. Seidler, María C. Camilión de Hurtado, Horacio E. Cingolani

Research output: Contribution to journalArticlepeer-review


Cardiac hypertrophy is often associated with an increased sympathetic drive, and both in vitro and in vivo studies have demonstrated the development of cardiomyocyte hypertrophy in response to either α- or β-adrenergic stimulation. Because an association between the Na+/H+ exchanger and cellular growth has been proposed, this study aimed to analyze the possible role of the antiporter in isoproterenol-induced cardiac hypertrophy. Isoproterenol alone (5 mg/kg IP once daily) or combined with a selective inhibitor of the Na+/H+ exchanger activity (3 mg · kg-1 · d-1 BIIB723) was given to male Wistar rats for 30 days. Sex- and age-matched rats that received 0.9% saline IP daily served as controls. Echocardiographic follow-up showed a 33% increase in left ventricular mass in the isoproterenol-treated group, whereas it did not increase in the isoproterenol+BIIB723-treated group. Heart weight-to-body weight ratio at necropsy was 2.44 ± 0.11 in controls and increased to 3.35 ± 0.10 (P < 0.05) with isoproterenol, an effect that was markedly attenuated by BIIB723 (2.82 ± 0.07). Intense cardiomyocyte enlargement and severe subendocardial fibrosis were found in isoproterenol-treated rats, and both effects were attenuated by BIIB723. Myocardial Na+/H+ exchanger activity and protein expression significantly increased in isoproterenol-treated rats compared with the control group (1.45 ± 0.11 vs 0.91 ± 0.05 arbitrary units, P < 0.05). This effect was significantly reduced by BIIB723 (1.17 ± 0.02, P < 0.05). In conclusion, our results show that Na+/H+ exchanger inhibition prevented the development of isoproterenol-induced hypertrophy and fibrosis, providing strong evidence in favor of a key role played by the antiporter in this model of cardiac hypertrophy.

Original languageEnglish (US)
Pages (from-to)1324-1329
Number of pages6
Issue number6
StatePublished - Jun 1 2003
Externally publishedYes


  • Adrenergic receptor agonists
  • Antiporters
  • Fibrosis
  • Hypertrophy, cardiac
  • Signal transduction

ASJC Scopus subject areas

  • Internal Medicine


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