Chronic treatment with a superoxide dismutase mimetic prevents vascular remodeling and progression of hypertension in salt-loaded stroke-prone spontaneously hypertensive rats

Abstract Oxidative stress has been implicated in the pathogenesis of hypertension. The aim of the present study was to determine whether increased generation of vascular superoxide anion (•O2−) contributes to blood pressure elevation by influencing vascular function and structure in severely hypertensive rats. Sixteen-week-old stroke-prone spontaneously hypertensive rats (SHRSP) (n = 12) were randomly divided into two groups to receive the superoxide dismutase mimetic, tempol (4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl) (1 mmol/L in drinking water) or tap water. Both groups were fed a high-salt diet (4% NaCl). Systolic blood pressure (SBP) was measured weekly for 6 weeks by the tail-cuff method. Rats were killed, and vascular structure (media:lumen ratio) and endothelial function (acetylcholine [Ach]–induced vasodilation) were assessed in small mesenteric arteries mounted as pressurized preparations. Vascular •O2− concentration was measured by lucigenin (5 μmol/L) chemiluminescence. Plasma total antioxidant status was assessed spectrophotometrically. The SBP increased significantly (P< .01) in the control group, whereas progression of hypertension was prevented in the tempol-treated group. Tempol reduced (P< .01) the media:lumen ratio (7.2% ± 0.01%) compared with that in controls (12.0% ± 0.01%). Maximal Ach-induced dilation was altered in control rats (40% ± 9%) but was not influenced by tempol (57% ± 1 7%). Vascular •O2− concentration was lower (P< .01) and plasma total antioxidant concentration was higher (P< .05) in the treated group compared with the control. In conclusion, tempol prevents progression of hypertension. These processes are associated with attenuated vascular remodeling, decreased vascular •O2− concentration, and increased antioxidant status. Our data suggest that oxidative stress plays an important role in vascular damage associated with severe hypertension in salt-loaded SHRSP.