Background: Sympathetic vasomotor hyperactivity and baroreflex dysfunction are involved in the development and maintenance of renovascular arterial hypertension. We hypothesized that angiotensin (Ang) II-dependent oxidative stress contributes to the pathophysiology of the two-kidney, one-clip (2K-1C) model.
Methods: The mean arterial pressure (MAP), baroreflex, and renal sympathetic nerve activity (rSNA) were evaluated after chronic administration of an antioxidant, vitamin C (vitC 150 mg/kg/day) in male Wistar 2K-1C rats. Additionally, the mRNA levels of Ang II subtype 1 receptor (AT(1)R), NAD(P)H oxidase subunits (p47phox and gp91phox), and major antioxidant enzymes were evaluated in the renal cortex.
Results: After vitC treatment, the MAP (170 +/- 4 vs. 133 +/- 6 mm Hg; P < 0.05) and rSNA (161 +/- 5 vs. 118 +/- 12 spikes/s; P < 0.05) were significantly reduced only in the 2K-1C group. VitC improved the baroreflex control of heart rate (HR) and rSNA. The expression of AT(1)R, p47phox, and gp91phox was elevated (51, 184, and 132%, respectively) in the clipped kidney of 2K-1C group. VitC downregulated AT(1)R in the clipped kidney (31%). Catalase (CAT) expression was reduced in clipped (70%) and nonclipped (83%) kidneys of 2K-1C rats. VitC treatment augmented the expression of glutathione peroxidase (GPx) in both clipped (185%) and nonclipped (212%) kidneys of the 2K-1C group.
Conclusions: The present study suggests a role for oxidative stress in the cardiovascular and sympathetic alterations in renovascular hypertension, associated with changes in the expression of AT(1)R, NAD(P)H oxidase subunits, and antioxidant enzymes in the kidney.