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

Author： Silva Kamila C. Rosales Mariana A. B. Lopes de Faria José B. Lopes de Faria Jacqueline M.

Publisher： Informa Healthcare

ISSN： 0271-3683

Source： Current Eye Research, Vol.35, Iss.6, 2010-06, pp. : 519-528

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Abstract

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 (NO_x⁻) 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.