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

Aim:To investigate the role of inducible nitric oxide synthase (iNOS)-derivednitric oxide (NO) in the cardioprotection of intermittent hypoxia (IH) against is-chemia/reperfusion (I/R) injury.Methods:Langendorff-perfused isolated rathearts were used to measure variables of left ventricular function during baselineperfusion,ischemia,and reperfusion period.Nitrate plus nitrite (NOx) content inmyocardium was measured using a biochemical method,iNOS mRNA and pro-tein expression in rat left ventricles were detected using reverse transcription poly-merase chain reaction (RT-PCR) and Western blot,respectively.Results:Myo-cardial function recovered better in IH rat hearts than in normoxic control hearts.The iNOS-selective inhibitor aminoguanidine (AG) (100μmol/L) significantlyinhibited 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 tothe corresponding baseline level,whereas there was no significant change in IHhearts.However,the NOx level in IH hearts was still higher than that of normoxichearts during ischemia and reperfusion period.AG 100μmol/L significantly di-minished the NOx content in IH and normoxic hearts during ischemia and reperfusignperiod.The baseline levels of iNOS mRNA and protein in IH hearts were higherthan those of normoxic hearts.Compared to the corresponding baseline level,iNOS mRNA and protein levels in normoxic rat hearts increased and those in IH rathearts decreased after reperfusion.The addition of AG 100μmol/L significantlydecreased iNOS mRNA and protein expression in IH rat hearts after I/R.Conclusion:IH upregulated the baseline level of iNOS mRNA and protein expres-sion leading to an increase in NO production,which may play an important role inthe cardiac protection of IH against I/R injury.