Antioxidative treatment reverses imbalances of nitric oxide synthase isoform expression and attenuates tissue-cGMP activation in diabetic rats.

Oxidative stress and impaired bioactivity of vascular nitric oxide (NO) play an important role in the pathogenesis of macro- as well as microangiopathic complications in diabetes mellitus. To determine the cause of this impaired bioactivity, we tested the effect of long-term hyperglycemia and antioxidative treatment on tissue-specific endothelial (e)NOS- and inducible (i)NOS-expression and the main target of NO action, cGMP, in diabetic rats. After 4 weeks of hyperglycemia, eNOS-mRNA expression was significantly down-regulated in all tissues tested.