Male/female differences in intracellular Na+regulation during ischemia/reperfusion in mouse heart

Kenichi Imahashi, Robert E. London, Charles Steenbergen, Elizabeth Murphy

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


We previously showed that β-adrenergic stimulation revealed male/female differences in susceptibility to ischemia/reperfusion (I/R) injury. To explore whether altered [Na+]i regulation is involved in the mechanism of this sex difference, we measured [Na+] i by 23Na NMR spectroscopy in isolated perfused mouse hearts. [Na+]i increased to 195 ± 3% (mean ± S.E.) of the pre-ischemic level at 20 min of ischemia in male hearts, whereas [Na+]i accumulation was slightly less in female hearts (176 ± 2%, P < 0.05). There was no significant difference in the recovery of contractile function after reperfusion (male: 30.6 ± 3.8%; female: 35.0 ± 1.9%; P > 0.05). If hearts were treated with isoproterenol (ISO, 10 nmol/l), males exhibited significantly poorer recovery of post-ischemic contractile function than females (male: 13.0 ± 1.9%; female: 28.1 ± 1.2%; P < 0.05), and a significantly higher [Na +]i accumulation during ischemia (male: 218 ± 8%; female: 171 ± 2%; P < 0.05). This ISO-induced male/female difference in [Na+]i accumulation or contractile function was blocked by the nitric oxide synthase inhibitor, Nω-nitro-L-arginine methyl ester (1 μmol/l). Furthermore, in ISO-treated hearts, the Na +/K+-ATPase inhibitor, ouabain (200 μmol/l) did not abolish the male/female difference in [Na+]i accumulation during I/R or functional protection. Thus the data show that the sex difference in the [Na+]i regulation is mediated through a NO-dependent mechanism, and the difference in susceptibility to I/R injury appears to result from a difference in Na+ influx.

Original languageEnglish (US)
Pages (from-to)747-753
Number of pages7
JournalJournal of Molecular and Cellular Cardiology
Issue number3
StatePublished - Sep 2004
Externally publishedYes


  • Ischemia
  • Nuclear magnetic resonance spectroscopy
  • Sexual dimorphisms
  • Sodium

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine


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