Biopterin regulation and its association with NOS activity in vascular endothelial cells

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Statin increased cellular biopterin by inducing GTPCH gene expression. This seems to enhance formation of NO and reudce uncoupling of NOS leading to NOS-mediated reduction of oxygen and formation of superoxide anions and hydrogen peroxide. Statin therefore increase eNOS activity by not only inducing eNOS itself but also increasing available BH4. This study indicates that statin increased stability of eNOS mRNA but not that of GTPCH mRNA, suggesting that upregulation of GTPCH mRNA by statin is induced by transcriptional activatoin.NO producibility was investigated in VSMC, in which BH4 synthesis is able only via salvage pathway but de novo pathway is disable, using 2,4-diamino-6-hydroxypyrimidine (DAHP), a, selective inhibitor of GTPCH. The present data shows that BH4, BH2, and sepiapterin dose- dependently increased NO production and increased intracellular biopterin levels. NO producibility as a functon of concentrations was BH4 << BH2 < sepiapterin, and similarly intracellular biopterin concentration was BH4 << BH2 < sepiapterin.