Mechanisms underlying recoupling of eNOS by HMG-CoA reductase inhibition in a rat model of streptozotocin-induced diabetes mellitus
OBJECTIVE: HMG-CoA reductase inhibitors have been shown to upregulate GTP
cyclohydrolase I (GTPCH-I), the key enzyme for tetrahydrobiopterin de novo synthesis and to
normalize tetrahydrobiopterin levels in hyperglycemic endothelial cells. We sought to
determine whether in vivo treatment with the HMG-CoA reductase inhibitor atorvastatin is
able to upregulate the GTPCH-I, to recouple eNOS and to normalize endothelial dysfunction
in an experimental model of diabetes mellitus. METHODS AND RESULTS: In male Wistar …
cyclohydrolase I (GTPCH-I), the key enzyme for tetrahydrobiopterin de novo synthesis and to
normalize tetrahydrobiopterin levels in hyperglycemic endothelial cells. We sought to
determine whether in vivo treatment with the HMG-CoA reductase inhibitor atorvastatin is
able to upregulate the GTPCH-I, to recouple eNOS and to normalize endothelial dysfunction
in an experimental model of diabetes mellitus. METHODS AND RESULTS: In male Wistar …
