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  • Title: Role of angiotensin II type 1 receptor on retinal vascular leakage in a rat oxygen-induced retinopathy model.
    Author: Nakamura H, Yamazaki M, Ohyama T, Inoue T, Arakawa N, Domon Y, Yokoyama T.
    Journal: Ophthalmic Res; 2009; 41(4):210-5. PubMed ID: 19451734.
    Abstract:
    AIM: To investigate the role of angiotensin type 1 (AT1) and type 2 (AT2) receptors in hypoxia-induced retinal vascular hyperpermeability. METHODS: Brown-Norway rat pups were exposed to hyperoxic conditions from postnatal day 7 (P7) to P12, and to subsequent normal air for 5 days [oxygen-induced retinopathy (OIR) model]. Olmesartan medoxomil (AT1 receptor antagonist; administered orally), PD123319 (AT2 receptor antagonist; administered subcutaneously) or a vehicle was administered once daily during the last 5 days. At P16, the retinal permeability was determined by measuring the leaked fluorescein-conjugated dextran concentration in the retina. The vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) alpha proteins in the retina were assessed by an ELISA and western blotting, respectively. RESULTS: Olmesartan medoxomil partially, but significantly, inhibited the retinal vascular hyperpermeability induced by hypoxia. In contrast, PD123319 did not show a significant effect. The VEGF and HIF-1alpha protein levels were significantly elevated in the OIR retina; however, there was no significant effect of olmesartan medoxomil on the expression of either protein. CONCLUSIONS: These results suggest that the AT1 receptor is, at least partly, responsible for hyperpermeability in the OIR rat retina via a mechanism independent of HIF-1 and VEGF expression.
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