Reversal of hyperglycemic preconditioning by angiotensin II: Role of calcium transport

Viktor Pastukh, Songwei Wu, Craig Ricci, Mahmood Mozaffari, Stephen Schaffer

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Myocardial cell death is an important contributor to the development of diabetic cardiomyopathy. It has been proposed that diabetes-mediated upregulation of the renin-angiotensin system leads to oxidative stress, the trigger for cardiomyocyte death and contractile dysfunction. However, the adverse effect of ANG II on the diabetic heart may extend beyond the development of the cardiomyopathy. ANG II also alters specific modulators of ischemic injury, such as PKC and calcium transport. Therefore, the present study examined the effect of ANG II on hyperglycemic preconditioning, a glucose-mediated condition associated with the elevation of PKC activity and alterations in calcium transport that render the cell resistant to hypoxia. Exposure of the glucose-treated cell to ANG II during the prehypoxic period blocked glucose-mediated cardioprotection. The reversal of hyperglycemic preconditioning was associated with enhanced accumulation of Ca2+ during hypoxia, an effect prevented by inhibition of the Na+/H+ exchanger and the T-type Ca2+ channel. The inhibitors of hypoxia-mediated Ca2+ accumulation also blocked the reversal of hyperglycemic preconditioning by ANG II. Thus ANG II and glucose treatment exert opposite actions on the Na+/H+ exchanger and the T-type Ca 2+ channel. Because those transporters are involved in hypoxia-mediated apoptosis, they are logical candidates for the beneficial effects of high glucose and the adverse effects of ANG II on the hypoxic cardiomyocyte.

Original languageEnglish (US)
Pages (from-to)H1965-H1975
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number4 57-4
DOIs
StatePublished - Apr 1 2005

Keywords

  • Apoptosis
  • Calcium overload
  • Hyperglycemia
  • Hypoxia
  • Protein kinase C
  • Sodium-hydrogen exchanger
  • T-type calcium channel

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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