Tempol, Vitamin C and Vitamin E Improve Endothelial Dysfunction, Regress Vascular Hypertrophy and Prevent Progression of Hypertension and Renal Dysfunction in Stroke-Prone Shr
Antioxidant vitamins reduce oxidative stress in vascular injury associated with atherosclerosis and balloon injury. The role of these agents in the pathogenesis of hypertension is unclear. We investigated effects of vitamins C and E and the superoxide dismutase (SOD) mimetic, tempol, on development of blood pressure, vascular structure and endothelial function in salt-loaded stroke-prone SHR (SHRSP). 16 week-old SHRSP (n=26) on a high salt diet (4% NaCl) were randomly divided into 4 groups: control (C), Vit C (1000 mg/d), Vit E (1000 IU/d) and tempol (1 mmol/d). Systolic blood pressure (SBP) and renal function were assessed weekly. 6 weeks after treatment rats were killed. Vascular structure (media:lumen ratio) and endothelial function (acetylcholine (Ach)-induced vasodilation) were assessed in small mesenteric arteries mounted as pressurized preparations. SBP increased from 204± to 265±6 mmHg in C group. Progression of hypertension was prevented in Vit C (234±4 mmHg), Vit E (227±11mmHg) and tempol (208±8 mmHg) groups. Development and severity of proteinuria was delayed in all treated groups compared with C. The media:lumen ratio was reduced (p<0.001) in the Vit E (7.4±0.5%) and tempol (7.2±0.01%) groups compared with C group (12±0.1%). Structure was not significantly altered in the Vit C group. Maximal Ach-induced dilation was significantly improved in all treated groups, particularly in the Vit C group (85±4 % vs C 40±9 %, p<0.01). In conclusion antioxidant vitamins and tempol prevent progression of hypertension and improve renal dysfunction in SHRSP. These processes are associated with improved endothelial function and regression of vascular hypertrophy in small arteries. Our data suggest that oxidative stress plays a role in vascular and renal damage associated with severe hypertension in salt-loaded SHRSP.