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Intermittent hypoxia conditioning (IHC) prevents NO overproduction and accumulation of 3‐nitrotyrosine in the myocardium of rats during ischemia and reperfusion
Author(s) -
Manukhina Eugenia B.,
Goryacheva Anna V.,
Chepurnova Daria A,
Belkina Ludmila M.,
Terekhina Olga L.,
Mallet Robert T.,
Downey H. Fred
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.669.13
The role of nitric oxide (NO) in prevention of ischemia and reperfusion (IR) injury is controversial. Earlier we showed that IHC protects the heart and endothelium from IR injury. Now, the role of NO‐dependent mechanisms in this protection was studied. Rats were subjected to normobaric IHC (5–8 cycles/d for 20 d, FIO2 9.5–10% for 5–10 min/cycle, with intervening 4 min normoxia), and control rats were sham‐conditioned. IR was produced by ligation of the left coronary artery for 30 min with 60‐min reperfusion. NO production was evaluated from plasma nitrite+nitrate (NOx). 3‐Nitrotyrosine (3‐NT) and HIF‐1α were measured by immunoblot. IHC tended to increase basal NOx (6.8±0.5 vs 8.1±0.4 μmol/L NOx, p=0.23) and prevented IR‐induced NO overproduction (14±1 vs 9.1±1.1 μmol/L NOx, p<0.005). Without IHC, IR‐induced NO overproduction was associated with significant 3‐NT accumulation in the left ventricle (142±8% vs 100±12% in control, p<0.01) but not in septum or aorta. In IHC rats, 3‐NT after IR was similar to that of control rats without IR. IHC induced marked accumulation of HIF‐1α in the left ventricle (220±38% vs 100±7% in control, p<0.005). HIF‐1α‐induced increase in NO production may prevent subsequent NO overproduction by negative feedback. Thus, IHC cardioprotection is associated with prevention of toxic effects of NO overproduction in the myocardium during IR. Support: RFBR grant 10‐04‐00980 .