The Expression Of GTPCH â…  In Diabetic Rats' Aorta

Objectives:It is known that the attenuate of endothelial-dependent vascular relaxation exists in diabetes mellitus and endothelial dysfunction in diabetes is characterized by decreased nitric oxide (NO) bioactivity and increased superoxide (SO) production,however,the cellular and biochemic mechanisms underlying the loss of endothelial NO bioavailability in endothelial dysfunction states has remained unclear.We have known that Tetrahydrobiopterin (BH4),an essential cofactor of endothelial NO synthase (eNOS), appear to be associated with the attenuate of endothelial-dependent vascular relaxation.NO is generated intracellularly from L-arginine via NO-synthase with the help of several cofactors, including tetrahydobiopterin. Interestingly, it has recently become evident that under certain conditions, when there is a lack of tetrahydrobiopterin, NO-synthase produces reactive oxygen species instead of NO. Reactive oxygen species counteract the effects of NO and also scavenge NO resulting in the formation of peroxynitrite (ONOO),which have been shown to have deleterious effects with respect to vascular function. GTP cyclohydrolase I (GTPCH I), the rate-limiting enzyme for the de novo BH4 synthesis,controls the intracellular concentration of BH4 .Recent research focuses on the genetic expression and the activity of GTPCH I. It is observed that the expression of GTPCH I mRNA and the level of BH4 decreased in cultured BAECs and STZ induced rats. NO was decreased and O₂^- was increased simultaneously. It suggests that high glucose results in endothelial dysfunction through decrease of GTPCH I mRNA expression.Then, did GTPCH I take part in the mechanisms of...