Uncoupling Endothelial Nitric Oxide Synthase Is Ameliorated by Green Tea in Experimental Diabetes by Re-establishing Tetrahydrobiopterin Levels

Abstract

The current study investigated the potential of green tea (GT) to improve uncoupling of endothelial nitric oxide synthase (eNOS) in diabetic conditions. In rats with streptozotocin-induced dia-betes, nitric oxide (NO) bioavailability was reduced by uncou-pling eNOS, characterized by a reduction in tetrahydrobiopterin (BH4) levels and a decrease in the eNOS dimer-to-monomer ratio. GT treatment ameliorated these abnormalities. Moreover, immor-talized human mesangial cells (ihMCs) exposed to high glucose (HG) levels exhibited a rise in reactive oxygen species (ROS) and a decline in NO levels, which were reversed with GT. BH4 and the activity of guanosine triphosphate cyclohydrolase I decreased in ihMCs exposed to HG and was normalized by GT. Exogenous administration of BH4 in ihMCs reversed the HG-induced rise in ROS and the decline in NO production. However, coadministra-tion of GT with BH4 did not result in a further reduction in RO