Rosuvastatin Decreases the Oxidative Stress in Retinas of Spontaneously Hypertensive Rats via the Inhibition of NADPH Oxidase Activity

Abstract

Abstract: : Purpose: The aim of this study was to assess the role of rosuvastatin (ROSU) administration on haemodynamic function and retinal oxidative stress in normotensive and hypertensive rats. Methods: At 10 weeks of age, spontaneously hypertensive rats (SHR, n=10) and normotensive Wistar Kyoto male rats (WKY, n=10) received either vehicle or ROSU (10 mg/kg/day) for 3 weeks by gavage. Systolic blood pressure was assessed every week. At the end of the treatment, reactive oxygen species (ROS) were determined in the aorta and in the retina with dihydroethidium staining (DHE, 5 µM) combined with DAPI and chemoluminescence evaluating NADPH oxidase activity (lucigenin, 0.5 µM). Results: Chronic treatment with ROSU did not lower plasma cholesterol levels. However, after 3 weeks of treatment, ROSU reduced arterial blood pressure in SHR rats (186 ± 2mm Hg, SHR versus 168 ± 2 mmHg, SHR + ROSU (p<0.01)). In aortas, DAPI/DHE florescence and NADPH oxidase activity were 25–30 % higher in control SHR compared with WKY (p<0.01). Moreover, we observed an increased oxidative stress in the inner layers of the retina up to 40–50% (p<0.01) in SHR vs WKY. DHE fluorescence was normalized by ROSU in SHR rat’s aorta and retinas (p<0.01). This effect was associated with the decrease of NADPH oxidase activity (p<0.01). Conclusions: These results are in accordance with the hypothesis that oxidative stress plays a crucial role in the pathogenesis of retinal and cardiovascular diseases including hypertension. In this model, the beneficial effects of ROSU, seems to be independent of its lipids lowering actions.

Keywords: oxidation/oxidative or free radical damage • pharmacology • retina