Troglitazone reverses the inhibition of nitric oxide production by high glucose in cultured bovine retinal pericytes

In the retinal microcirculation, there is a basal release of nitric oxide (NO) which maintains the retinal blood flow. The proportions of endothelial cells and pericytes in the retinal capillaries are almost equal, so pericytes appear to play a important role in the regulation of microcirculatory hemodynamics in the retina. It has been suggested that the pathogenesis of early diabetic retinopathy may involve a reduced bioavailability or diminished production of NO. In this study, we investigated the role of troglitazone, a potent agonist of peroxisome proliferator activated receptor-gamma (PPAR gamma) used for the treatment of diabetes, on the NO release and the effect of exposure to high glucose on the production of NO in cultured bovine retinal pericytes. Troglitazone significantly increased NO production and iNOS expression after 24 hr in a dose-and PPAR gamma-dependent manner. Elevation Of D-glucose, but not L-glucose, from 5.5 to 30 mm for 24 hr decreased NO production, but co-treatment with troglitazone reversed high glucose-induced inhibition of NO production as well as iNOS expression. In conclusion, high glucose inhibits iNOS expression and subsequently NO synthesis in cultured bovine retinal pericytes, and troglitazone restores the NO production. (c) 2005 Elsevier Ltd. All rights reserved.