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5,6,7,8-Tetrahydrobiopterin (BH 4 ) is an csscntial cofactor for production of nitric oxide (NO) by N O synthase (NOS). Nitric oxide (NO) is an important signaling mo!ecu!e for the regulation o f vita! functions such as vascular tone, neurotransmission and immune surveiüance. Accumu!ated evidences show that although NOS mainly re!eases N O under nonnal conditions, NOS also produces Superoxide anion and hydrogen peroxide when BH 4  is decreased, suggesting the possibility that NOS is a source of reactive oxygen species (ROS) under pathological conditions. In fact, supplementation of BH 4  restores N O production and availability in various diseases including hyperlipidemia, diabetes, hypertension and ischemia-reperfusion. Moreover, recent studies show that administration o f BH 4  protects tissues against ischemia-reperfusion injuiy in heart, stomach and liver. Oxidative stress is a common mechanism underlying the development of vascular diseases and reperfusion injury. Regulation of BH 4  levels under oxidative stress is important to understand the role of BH 4  on the development of vascular diseases and reperfusion injury. We recently described that oxidative stress transiently decreased BH 4  levels, and then markedly increased its levels in vascular endothelial cells. Supplementation of BH 4  appears to be important therapeutic strategies in vascular diseases and reperfusion injury, and induction of BH 4  synthesis may endogenous defense system against oxidative stress-mediated cardiovascular diseases.

Beneficial Role of Tetrahydrobiopterin on Various Cardiovascular Diseases and Regulation of its Levels under Pathological Conditions