Nicardipine prevents calcium loading and ''oxygen paradox'' in anoxic single rat myocytes by a mechanism independent of calcium channel blockade

O. Hano, H. S. Silverman, P. S. Blank, E. D. Mellits, R. Baumgardner, E. G. Lakatta, M. D. Stern

Research output: Contribution to journalArticle

Abstract

The protective effect of nicardipine (1 and 4 μM) against reoxygenation injury was studied in an unstimulated rat single myocyte oxygen paradox model in comparison with control (no drug) or nifedipine (1 μM). Either concentration of nicardipine was strongly, protective, approximately doubling the duration of ATP depletion (rigor) that cells could withstand without undergoing hypercontracture when reoxygenated. Nifedipine (1 μM), which matched the negative inotropic effect of nicardipine (4 μM) (as measured by extent of shortening when stimulated), had no protective effect against reoxygenation injury. Neither drug affected the time to rigor, which is a measure of the rate at which the resting cell consumes its endogenous glycogen stores during anaerobic metabolism. Intracellular calcium, measured with the fluorescent probe indo-1, which partitions into both cytosol and mitochondria, rose progressively throughout the rigor period. This rise in calcium was almost totally suppressed by nicardipine (1 μM) but was unaffected by nifedipine. We conclude that nicardipine possesses a direct protective effect on the myocardium not shared by all dihydropyridines. This effect is associated with the prevention of intracellular, and probably mitochondrial, calcium loading but is probably not due to blockade of the L-type calcium channel or reduction of metabolic rate.

Original languageEnglish (US)
Pages (from-to)1500-1505
Number of pages6
JournalCirculation research
Volume69
Issue number6
DOIs
StatePublished - Jan 1 1991

Keywords

  • Calcium
  • Dihydropyridine
  • Hypoxia
  • Myocyte
  • Nicardipine
  • Nifedipine

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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