Reduction of inducible nitric oxide synthase via angiotensin receptor blocker prevents the oxidative retinal damage in diabetic hypertensive rats.
OBJECTIVE
To investigate if nitric oxide (NO) system contributes to the beneficial effect of angiotensin II type 1 receptor (AT(1)) 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.
Silva
Kamila C
KC
Renal Pathophysiology Laboratory, Investigation on Diabetes Complications, Faculty of Medical Sciences (FCM), State University of Campinas (Unicamp), Campinas, São Paulo, Brazil.
Rosales
Mariana A B
MA
de Faria
José B Lopes
JB
de Faria
Jacqueline M Lopes
JM
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000284:Administration, Oral; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D003930:Diabetic Retinopathy / Q000517:prevention & control*; D015536:Down-Regulation; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D009566:Nitrates / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D009994:Osmolar Concentration; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D012160:Retina / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D015854:Up-Regulation
D047228:Angiotensin II Type 1 Receptor Blockers; D015415:Biomarkers; D009566:Nitrates; D009573:Nitrites; D014443:Tyrosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D003849:Deoxyguanosine; D019808:Losartan