Reduction of Inducible Nitric Oxide Synthase via Angiotensin Receptor Blocker Prevents the Oxidative Retinal Damage in Diabetic Hypertensive Rats

• Published in: Current eye research 2010-06, Vol.35 (6), p.519-528
• Main Authors: Silva, Kamila C., Rosales, Mariana A. B., Lopes de Faria, José B., Lopes de Faria, Jacqueline M.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Angiotensin II Type 1 Receptor Blockers - administration & dosage; Angiotension II type 1 receptor blocker; Animals; Biomarkers - metabolism; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - metabolism; Diabetes Mellitus, Experimental; Diabetic retinopathy; Diabetic Retinopathy - prevention & control; Down-Regulation; Inducible nitric oxide synthase; Losartan - administration & dosage; Male; Nitrates - metabolism; Nitric oxide end products; Nitric Oxide Synthase Type II - metabolism; Nitrites - metabolism; Osmolar Concentration; Oxidation-Reduction - drug effects; Oxidative stress; Rats; Rats, Inbred SHR; Retina - metabolism; Superoxide Dismutase - metabolism; Tyrosine - metabolism; Up-Regulation
• ISSN: 0271-3683; 1460-2202
• DOI: 10.3109/02713681003664923

Purpose: To investigate if nitric oxide (NO) system contributes to the beneficial effect of angiotensin II type 1 receptor (AT1) blocker losartan in the retina of diabetic spontaneously hypertensive rats (SHR). Methods: Diabetic SHR were randomized to receive oral treatment with losartan (DM-SHRLos). After 20 days, the rats were euthanized and the retinas collected. Results: Diabetic SHR rats exhibited a significant increase in glial fibrillary acidic protein (GFAP) and decrease in occludin, markers of early diabetic retinopathy (DR). The oxidative status, evaluated by NO end-products (NOx−) levels along with the antioxidative system superoxide dismutase, revealed an accentuated imbalance in favor to oxidants in DM-SHR leading to a higher tyrosine nitration and DNA damage. The inducible NO synthase (iNOS) was also elevated in DM-SHR rats. The treatment with losartan ameliorated all of the above alterations. Conclusions: Oral treatment with losartan reduces iNOS expression and reestablishes the redox status, thus ameliorating the early markers of DR in a model of diabetes and hypertension.