Role of tetrahydrobiopterin on ischemia-reperfusion injury in isolated perfused rat hearts

Aim it has recently been shown that nitric oxide synthase in the presence of suboptimal levels of tetrahydrobiopterin (BH4), an essential cofactor of nitric oxide synthase, may favor increased production of oxygen free radicals. This study was designed to define the role of BH4 in myocardial ischemia-reperfusion injury. Methods. Isolated perfused rat hearts were subjected to 37degreesC ischemia and reperfusion. Hearts were received with BH4 or vehicle for 5 min just before ischemia and during the first 5 min of the reperfusion period. The effects of BH4 on left ventricular function, myocardial contents of lipid peroxidation and high energy phosphates, and levels of lactate dehydrogenase and nitrite plus nitrate in perfusate before ischemia and after reperfusion were estimated. Moreover, the effect of BH4 given with 2,4-diamino-6-hydroxypyriniidine (DAUP), a selective inhibitor of BH4 production, intraperitoneally 24 h before the experiments were estimated. Results. BH4 improved contractile and metabolic abnormalities in reperfused hearts. Furthermore, BH4 significantly alleviated ischemic contracture during ischemia, and restored diminished perfusate levels of nitrite plus nitrate after reperfusion. On the other hand, DAHP-treatment aggravated ischemia-reperfusion induced functional and metabolic abnormalities. Administration of BH4 improved DAHP-induced functional and metabolic abnormalities. Conclusion. Results demonstrated that BH4 lessens ischemia-reperfusion injury in isolated perfused rat hearts. Conversely, deficiency of BH4 seems to accelerate endothelial dysfunction and myocardial ischemiareperfusion injury. Present data may be compatible with the hypothesis that nitric oxide synthase in the presence of insufficiency of BH4 serve as the cause of oxidative injury.