The Role of Tetrahydrobiopterin and Dihydrobiopterin in Ischemia/Reperfusion Injury When Given at Reperfusion

[摘要] Reduced nitric oxide (NO) bioavailability and increased oxidative stress are major factors mediating ischemia/reperfusion(I/R) injury.Tetrahydrobiopterin (BH4) is an essential cofactor of endothelial NO synthase (eNOS) to produce NO, whereas dihydrobiopterin (BH2) can shift the eNOS product profile from NO to superoxide, which is further converted to hydrogen peroxide (H2O2) and cause I/R injury.The effects ofBH4andBH2on oxidative stress and postreperfused cardiac functions were examined in ex vivo myocardial and in vivo femoral I (20 min)/R (45 min) models.In femoral I/R,BH4increased NO and decreasedH2O2releases relative to saline control, and these effects correlated with improved postreperfused cardiac function.By contrast,BH2decreased NO release relative to the saline control, but increasedH2O2release similar to the saline control, and these effects correlated with compromised postreperfusedcardiac function.In conclusion, these results suggest that promoting eNOS coupling to produce NO and decreaseH2O2may be a key mechanism to restore postreperfusedorgan function during early reperfusion.

[学科分类] 药学