Attenuated Development of Hypertension by Antioxidant Vitamins in Stroke-Prone Shr Is Associated with Increased Vascular Superoxide Dismutase Activity and Decreased Oxidative Stress.
Oxidative stress has been implicated in the pathophysiology of cardiovascular diseases. We investigated effects of antioxidant vitamins and tempol, superoxide dismutase (SOD) mimetic, on vascular superoxide anion (×O2-) concentration, NADPH oxidase activity, SOD activity, plasma antioxidant levels and blood pressure in stroke-prone SHR (SHRSP). 16 week-old SHRSP on a high salt diet (4%NaCl) were divided into 4 groups: control (C), Vit C (1000mg/day), Vit E (1000 U/day) and tempol (1 mmol/d). Systolic blood pressure (SBP) and antioxidant status were measured weekly for 6 weeks. Aortic ×O2-concentration and NADPH oxidase activity were measured by luminometry using lucigenin (5 μmol/L) and aortic SOD activity and total plasma antioxidant status were measured using a spectrophotometric assay system. SBP and plasma antioxidant levels were similar in all groups prior to treatment. Table demonstrates results after 6 weeks treatment. Data are means ± SEM. Data from this study demonstrate that antioxidant vitamins and tempol attenuate the development of hypertension in SHRSP. This is associated with decreased vascular ×O2- production, increased activity of SOD and increased plasma antioxidant concentrations. We demonstrate the novel findings that Vits E and C induce their antioxidant effects, in part, by stimulating SOD activity. Thus increased oxidative stress is an important factor underlying vascular changes associated with severe hypertension in SHRSP.