Difference in the mechanisms for compensating ischemic acidosis in diabetic rat hearts

Hideo Kusuoka, Shinichi Matsuda, Makoto Ishikawa, Keiko Koga, Toyoki Mori, Hitoshi Yamaguchi, Tsunehiko Nishimura

Research output: Contribution to journalArticle

Abstract

To elucidate the difference in the mechanisms for alkalization during ischemic acidosis between diabetic and non-diabetic hearts, intracellular pH (pH(i)) was measured by phosphorus-31 magnetic resonance spectroscopy. Diabetes was induced by the injection of streptozotocin. The accumulation of proton ion (ΔH+) during 15 min global ischemia at 37°C was calculated from pH(i). There were no significant differences in ΔH+ between diabetic (DM: 0.54 ± 0.03 μmol/l, n = 6; mean ± S.E.M.) and non-DM hearts (0.57 ± 0.04, n = 6), when perfused with bicarbonate buffer. However, perfusion with HEPES buffer revealed a significant increase of ΔH+ in DM (0.85 ± 0.07, n = 5) compared with non-DM (0.61 ± 0.06, n = 5; P < 0.05). On the contrary, the addition of a Na+/H+ exchange inhibitor (EIPA; 1 μmol/l) to bicarbonate buffer significantly increased ΔH+ in non-DM (1.09 + 0.10, n = 4) compared with DM (0.71 ± 0.03, n = 5; P < 0.01). Perfusion with HEPES buffer and EIPA equally increased ΔH+ in both groups (DM 1.13 ± 0.13, n = 4; non-DM 1.15 ± 0.14, n = 4). Thus, the activity of Na+/H+ exchanger during ischemic acidosis, assessed as the increase of ΔH+ induced by addition of EIPA to bicarbonate buffer, was higher in non-DM (0.52) than DM (0.17). In contrast, the contribution of bicarbonate-dependent systems evaluated by the deference of ΔH+ between the bicarbonate buffer and the HEPES buffer was markedly bigger in DM (0.31) than non-DM (0.04). These results indicate that Na+/H+ exchange is a major mechanism to compensate ischemic acidosis in non-DM hearts, whereas bicarbonate-dependent systems compensate the depressed activity of Na+/H+ exchange in DM.

Original languageEnglish (US)
Pages (from-to)1643-1649
Number of pages7
JournalJournal of Molecular and Cellular Cardiology
Volume30
Issue number8
DOIs
StatePublished - Aug 1998

Keywords

  • Acidosis
  • Bicarbonate-dependent systems
  • Diabetes mellitus
  • EIPA
  • Ischemia
  • Na/H exchanger
  • Phosphorus magnetic resonance spectroscopy

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Kusuoka, H., Matsuda, S., Ishikawa, M., Koga, K., Mori, T., Yamaguchi, H., & Nishimura, T. (1998). Difference in the mechanisms for compensating ischemic acidosis in diabetic rat hearts. Journal of Molecular and Cellular Cardiology, 30(8), 1643-1649. https://doi.org/10.1006/jmcc.1998.0729