Tetrahydrobiopterin improves endothelium-dependent vasodilation in nitroglycerin-tolerant rats

Tolerance to nitroglycerin is caused by a nitroglycerin-mediated increase i n vascular superoxide anion production. Administration of tetrahydrobiopter in (co-factor for endogenous nitric oxide (NO) formation) may potentially i nfluence nitroglycerin tolerance in at least two different ways. Firstly, t etrahydrobiopterin may act as a scavenger of the nitroglycerin-mediated pro duction of superoxide anions. Secondly, tetrahydrobiopterin may protect end othelial NO synthesis from the deleterious effects of increased oxidative s tress. This study investigates whether in vivo nitroglycerin tolerance is a ffected by tetrahydrobiopterin supplementation and assesses the in vivo rol e of tetrahydrobiopterin in endogenous NO-mediated vasodilation in normal a nd nitroglycerin-tolerant rats. The results show that tetrahydrobiopterin d oes not affect nitroglycerin-derived, NO-mediated vasodilation, but reduces baseline mean arterial blood pressure (by 8 mm Hg, P < 0.05) and normalize s endothelium-dependent responses to N-G-monomethyl-L-arginine (L-NMMA) (fr om 7 <plus/minus> 1 to 22 +/- 4 mm Hg, P < 0.05) in nitroglycerin-tolerant rats. It is concluded that altered bioavailability of tetrahydrobiopterin i s involved in the pathophysiology of endothelial dysfunction seen in nitrog lycerin tolerance. <(c)> 2001 Elsevier Science B.V. All rights reserved.