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 (PPARgamma) 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 24hr in a dose-and PPARgamma-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.
Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, South Korea. jtkim@cau.ac.kr
Jaetaek
J
Kim
Yeon-sahng
YS
Oh
Soon-hyun
SH
Shinn
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002417:Cattle; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D047495:PPAR gamma / Q000819:agonists; D020286:Pericytes / Q000187:drug effects* / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
D002839:Chromans; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D000077288:Troglitazone; D005947:Glucose