Anti-inflammatory effects of tetrahydrobiopterin on early rejection in renal allografts: modulation of inducible nitric oxide synthase.

SPECIFIC AIMTo assess whether therapy with tetrahydrobiopterin (BH4) diminishes oxygen radical stress and improves nitric oxide (NO) levels after allogenic kidney transplantation in a rat model. To relate such changes to modulation of iNOS function.PRINCIPAL FINDINGS1. Effect of sepiapterin on intra graft superoxide production in renal allograftsOxidative stress is thought to play a major role in endothelial activation in transplanted organs. It has been suggested that NO synthase (NOS) enzyme can act as a source of superoxide (O2−) production in vivo. To assess the contribution of NOS-mediated O2− production associated with early rejection of renal grafts, we performed syngenic (LEW to LEW) and allogenic (BN to LEW) kidney transplantations in rats and measured intragraft O2− production using lucigenin-enhanced chemiluminescence. As a result of ischemia-reperfusion injury, 24 h after syngenic kidney transplantation O2− production was modestly elevated in the isografts compared with O2− production in nontr...