P-197: Role of blood pressure control with irbesartan and omapatrilat on the retineal damage in an experimental model of type 2 DM and hypertension

Among other factors, systemic hypertension exarcebates diabetic retinopathy. In vitro angio II and hyperglucemia (1) stimulates expression of vascular endothelial cell specific angiogenic factor (VEGF) which has been implicated in the pathogenesis of diabetic retinopathy (in humans and in experimental models) The aim of the present work is to examinate if RAS blockade provides together with BP control retinoprotective effects on the progression of retinal damage. For this propose, we compared the effect of treatment with Irbesartan (AT1 receptor antagonist) and Omapatrilat, a vasopeptidase inhibitor in an experimental model of type 2 diabetes mellitus and hypertension. Forty four male zucker rats of 5-6 weeks of age were subjected to left unilateral nefrectomy. Two weeks later, animals were randomly allocated to one of three different groups and followed during 8 months. Irbesartan group (IRBE) was treated with 50 mg/Kg/day. Omapatrilat group (OMA) 40 mg/Kg/day and Control group (CONTROL) received only vehicle. Both, drugs and vehicle were administered by gavage. At the end of follow-up, rats were sacrified and both eyes were removed for histological and molecular studies performed by evaluation of VEGF and PCNA (as a marker of cell proliferation) protein content by Western blot. No differences were found in the light microscopy retineal studies. VEGF and PCNA expression were markedly increased in control animals that were indetectable in IRBE and OMA groups. A positive effect of drugs treatment has been found in the present model. These molecular findings are not correlated with light microscopy studies, probably due to low power of the last technique versus molecular studies, or because molecular changes occur before morphological damage. (See Figure)