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in chronically hypoxic rat myocardium: involvement in cardioprotection
1 Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic
2 Centre for Experimental Cardiovascular Research, Prague, Czech Republic
* To whom correspondence should be addressed. E-mail: kolar{at}biomed.cas.cz.
We examined the role of protein kinase C (PKC) in the cardioprotective mechanism induced by long-term adaptation to chronic intermittent hypoxia. Adult male Wistar rats were exposed to hypobaric hypoxia of 7000 m for 8 h/day, 5 days/week; the total number of exposures was 24-32. A control group was kept under normoxic conditions. The Western blot analysis of PKC isoforms
and
was performed in the cytosol and three particulate fractions of left ventricular myocardium. Infarct size was determined in open-chest animals subjected to 20-min coronary artery occlusion and 3-h reperfusion. PKC inhibitors chelerythrine (1 mg/kg or 5
mg/kg) or rottlerin (selective for PKC
isoform; 0.3 mg/kg) were administered intravenously as a
single bolus 15 min before ischemia. Chronic hypoxia had no effect on the expression and distribution of PKC
. The relative amount of PKC
increased in the cytosol and nuclearcytoskeletal,
mitochondrial and microsomal fractions of chronically hypoxic myocardium by 100%, 212%, 237%, and 146%, respectively, compared to corresponding normoxic values.
Chronic hypoxia decreased the size of myocardial infarction (normalized to the area at risk) by
about one-third on the average (P<0.05). Both doses of chelerythrine tended to reduce infarction
in controls and only its high dose completely abolished the improvement of ischemic tolerance in
hypoxic hearts (P<0.05). Rottlerin attenuated the infarct size-limiting effect of chronic hypoxia
(P<0.05) and it had no effect in controls. These results suggest that chronic intermittent hypoxiainduced
cardioprotection in rats is partially mediated by PKC
; the contribution of other isoforms remains to be determined.
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