Original Articles

Inducible nitric oxide synthase contributes to intermittent hypoxia against ischemia/reperfusion injury

Authors: Hai-lei DING, Hai-feng ZHU, Jian-wen DONG, Wei-zhong ZHU, Wei-wei YANG, Huang-tian YANG, Zhao-nian ZHOU

Abstract

Aim: To investigate the role of inducible nitric oxide synthase (iNOS)-derived
nitric oxide (NO) in the cardioprotection of intermittent hypoxia (IH) against ischemia/
reperfusion (I/R) injury. Methods: Langendorff-perfused isolated rat
hearts were used to measure variables of left ventricular function during baseline
perfusion, ischemia, and reperfusion period. Nitrate plus nitrite (NOx) content in
myocardium was measured using a biochemical method. iNOS mRNA and protein
expression in rat left ventricles were detected using reverse transcription polymerase
chain reaction (RT-PCR) and Western blot, respectively. Results: Myocardial
function recovered better in IH rat hearts than in normoxic control hearts.
The iNOS-selective inhibitor aminoguanidine (AG) (100 μmol/L) significantly
inhibited the protective effects of IH, but had no influence on normoxic rat hearts.
The baseline content of NOx in IH hearts was higher than that in normoxic hearts.
After 30 min ischemia, the NOx level in normoxic hearts increased compared to
the corresponding baseline level, whereas there was no significant change in IH
hearts. However, the NOx level in IH hearts was still higher than that of normoxic
hearts during ischemia and reperfusion period. AG 100 μmol/L significantly diminished
the NOx content in IH and normoxic hearts during ischemia and reperfusion
period. The baseline levels of iNOS mRNA and protein in IH hearts were higher
than those of normoxic hearts. Compared to the corresponding baseline level,
iNOS mRNA and protein levels in normoxic rat hearts increased and those in IH rat
hearts decreased after reperfusion. The addition of AG 100 μmol/L significantly
decreased iNOS mRNA and protein expression in IH rat hearts after I/R.
Conclusion: IH upregulated the baseline level of iNOS mRNA and protein expression
leading to an increase in NO production, which may play an important role in
the cardiac protection of IH against I/R injury.
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