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

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 micromol/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%+/-17%). 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.