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 (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.
ACKNOWLEDGMENTS
This work was supported by the State of São Paulo Research Foundation (FAPESP), under the document no. 05/58189-5 and 08/54068-7. Kamila C. Silva was in receipt of a scholarship from the FAPESP and Mariana A. B. Rosales from Coordination for the Improvement of Higher Education Personnel (CAPES). The authors also thank Sandra Regina Brambilla, Juliana Cristina Amadeu, and Aline Macedo Faria for technical assistance and Marcelo G. de Oliveira and Gabriela F. P. de Souza for assistance in NO chemiluminescence analyzer.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.