Chronic antioxidant treatment improves arterial renovascular hypertension and oxidative stress markers in the kidney in Wistar rats.
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.
Nishi
Erika Emy
EE
Cardiovascular Division, Department of Physiology, Universidade Federal de São Paulo, São Paulo, Brazil.
Oliveira-Sales
Elizabeth Barbosa
EB
Bergamaschi
Cássia T
CT
Oliveira
Thais Galvão César
TG
Boim
Mirian A
MA
Campos
Ruy R
RR
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D005979:Glutathione Peroxidase / Q000378:metabolism; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology* / Q000294:innervation; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000503:physiopathology
D000975:Antioxidants; D015415:Biomarkers; D044140:Receptor, Angiotensin, Type 1; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D001205:Ascorbic Acid