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

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Abstract
Oxidative stress contributes to the development of early transplant failure. As nitric oxide synthases (NOS) can act as sources of superoxide, we investigated the effect of the NOS cofactor tetrahydrobiopterin (BH4) on oxyradical production and early rejection in a rat kidney transplantation model. Allograft transplantation (Brown Norway to Lewis) showed more renal superoxide production and monocyte infiltration when compared with isografts (Lewis to Lewis). Administration of the stable BH4 precursor sepiapterin had no effect on superoxide production in the isografts (51 +/- 10 vs. 69 +/- 17 cps/10 mg protein), but led to a marked decrease in superoxide production in the allografts (116 +/- 11 vs. 60 +/- 6 cps/10 mg protein;