TETRAHYDROBIOPTERIN RESTORES ENDOTHELIAL FUNCTION IN HYPERCHOLESTEROLEMIA

In hypercholesterolemia, impaired nitric oxide activity has been assoc iated with increased nitric oxide degradation by oxygen radicals. Defi ciency of tetrahydrobiopterin, an essential cofactor of nitric oxide s ynthase, causes both impaired nitric oxide activity and increased oxyg en radical formation. In this study we tested whether tetrahydrobiopte rin deficiency contributes to the decreased nitric oxide activity obse rved in hypercholesterolemic patients. Therefore, L-mono-methyl-argini ne to inhibit basal nitric oxide activity, serotonin to stimulate nitr ic oxide activity, and nitroprusside as endothelium-independent vasodi lator were infused in the brachial artery of 13 patients with familial hypercholesterolemia and 13 matched controls. The infusions were repe ated during coinfusion of L-arginine (200 mu g/kg/min), tetrahydrobiop terin (500 mu g/min), or the combination of both compounds. Forearm va somotion was assessed using forearm venous occlusion plethysmography a nd expressed as ratio of blood flow between measurement and control ar m (M/C ratio). Tetrahydrobiopterin infusion alone did not alter M/C ra tio. Both the attenuated L-mono-methyl-arginine-induced vasoconstricti on as well as the impaired serotonin-induced vasodilation were restore d in patients during tetrahydrobiopterin infusion. Tetrahydrobiopterin had no effect in controls. In conclusion, this study demonstrates res toration of endothelial dysfunction by tetrahydrobiopterin suppletion in hypercholesterolemic patients.