Alteration of intracellular Na+ during ischemia in diabetic rat hearts: The role of reduced activity in Na+/H+ exchange against stunning

Kenichi Imahashi, Katsuji Hashimoto, Hitoshi Yamaguchi, Tsunehiko Nishimura, Hideo Kusuoka

Research output: Contribution to journalArticle

Abstract

To elucidate the contribution of reduced activity of Na+/H+ exchange in streptozotocin-induced diabetic hearts against stunning. intracellular Na+ concentration ([Na+](i)) was measured in isolated rat hearts using 23Na-MRS. The recovery of left ventricular developed pressure in hearts reperfused after 15 min global ischaemia at 37°C was significantly better in diabetic ones (102.9 ± 2.0% of pre-ischemic level, mean ± S.E., n = 6; P < 0.05), and non-diabetic ones pre-treated with potent Na+/H+ exchange inhibitor, EIPA (1 μmol/l; 93.8 ± 2.3%, n = 5; *P < 0.05) than non-treated. non-diabetic hearts (75.1 ± 2.5%, n = 8). When diabetic hearts were pre-treated with EIPA, the recovery (101.2 ± 2.6%, n = 5) was identical to that of non-treated, diabetic hearts, [Na+](i) in non-diabetic hearts increased to 329.1 + 8.1% of pre-ischemic level during 15 min ischemia, whereas the increase in [Na+](i) in diabetic hearts significantly suppressed to 199.8 ± 10.3% (P < 0.001). EIPA attenuated the increase of [Na+](i) during ischemia to 189.1 ± 9.0% in non-diabetic hearts (P < 0.001) and to 155.3 ± 4.6% in diabetic hearts (P < 0.05). Thus, the EIPA-dependent Na+ accumulation during ischemia, i.e. Na+ influx probably mostly via Na+/H+ exchange was smaller in diabetic hearts by 69.7% compared with that in non-diabetic hearts. These results indicate that the cardiac protection against stunning in streptozotocin-induced diabetic hearts is mediated by the attenuation of Na+ accumulation during ischemia, which is caused by the reduced activity in Na+/H+ exchanger.

Original languageEnglish (US)
Pages (from-to)509-517
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume30
Issue number3
DOIs
StatePublished - Mar 1998

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Keywords

  • Dy(PPP)
  • Dy(TTHA)
  • EIPA
  • Ischemia/reperfusion
  • Na-MRS
  • Streptozotocin
  • [Na](i)

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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