The 4-amino analogue of tetrahydrobiopterin efficiently prolongs murine cardiac-allograft survival

We tested the 4-amino analogue of tetrahydrobiopterin (H(4)aminobiopterin), a novel pterin-based inhibitor of nitric oxide synthases, for its efficacy in a murine cardiac-transplant model employing an improved cuff technique. We treated groups of 5 animals each for the first 7 post-operative days wi th various doses of H(4)aminobiopterin, with Cyclosporin A (15 mg/kg/day), or no treatment. H(4)aminobiopterin (3 times 50 mg/kg/day) proved to be as efficient as high-dose Cyclosporin A (15 mg/kg/day) in prolonging allograft survival and in suppressing histologic changes caused by the immunoreactio n. Surprisingly, the doses of H(4)aminobiopterin effective in prolonging al lograft survival did not change the plasma nitrite plus nitrate, or the exp ression of inducible nitric oxide synthase, interferon-gamma, tumor necrosi s factor-alpha, and B7-1 (CD80), indicating that H(4)aminobiopterin may act through a novel, yet undiscovered mechanism.