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

Park, J.B., Touyz, R.M. , Chen, X. and Schriffin, E.L. (2002) Chronic treatment with a superoxide dismutase mimetic prevents vascular remodeling and progression of hypertension in salt-loaded stroke-prone spontaneously hypertensive rats. American Journal of Hypertension, 15(1), pp. 78-84. (doi: 10.1016/S0895-7061(01)02233-6)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Touyz, Professor Rhian
• Authors: Park, J.B., Touyz, R.M., Chen, X., and Schriffin, E.L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: American Journal of Hypertension
• ISSN: 0895-7061
• ISSN (Online): 1941-7225