title: Oxidative stress contributes to renovascular hypertension.
abstract: BACKGROUND
  Oxidative stress is a state in which excess reactive oxygen species (ROS) overwhelm endogenous antioxidant systems. It is known that this state has been involved in the development of hypertension. On the basis of previous data, we hypothesized that overactivity of NAD(P)H oxidase-derived ROS and the lowered activity of CuZnSOD, an endogenous antioxidant within the rostral ventrolateral medulla (RVLM), could contribute to 2K-1C (two-kidney one-clip) hypertension. Moreover, to test the functional significance of whether oxidative stress was involved in the maintenance of sympathetic vasomotor tone and blood pressure in 2K-1C hypertension, we administered Ascorbic Acid (Vit C), an antioxidant, into the RVLM or systemically.
  
  
  METHODS
  Experiments were performed in male Wistar rats (6 weeks after renal surgery--Goldblatt hypertension model--2K-1C). The mRNA expression of NAD(P)H oxidase subunits (p47phox and gp91phox) and CuZnSOD were analyzed in the RVLM using real-time PCR technique. The mean arterial blood pressure, heart rate, and renal sympathetic nerve activity were analyzed. Blood samples were collected and measured using thiobarbituric acid-reactive substances (TBARS).
  
  
  RESULTS
  The mRNA expression of NAD(P)H oxidase subnits (p47phox and gp91pox) was greater in 2K-1C compared to the control group in the RVLM, and CuZnSOD expression was similar in both groups. In the RVLM, Vit C resulted in a fall in arterial pressure and in the sympathetic activity only in the 2K-1C rats. Thiobarbituric acid-reactive substances (TBARS) were significantly greater in 2K-1C rats and the acute infusion of Vit C significantly decreased arterial pressure and renal sympathetic activity in 2K-1C.
  
  
  CONCLUSIONS
  The results support the idea that an increase in oxidative stress within the RVLM and systemically plays a major role in maintaining high arterial blood pressure and sympathetic drive in 2K-1C hypertension.
authors: Cardiovascular Division, Department of Physiology, Federal University of São Paulo, Santos, São Paulo, Brazil.
authors: Elizabeth B
authors: EB
authors: Oliveira-Sales
authors: Adriana P
authors: AP
authors: Dugaich
authors: Bruno A
authors: BA
authors: Carillo
authors: Nayda P
authors: NP
authors: Abreu
authors: Mirian A
authors: MA
authors: Boim
authors: Paulo J
authors: PJ
authors: Martins
authors: Vânia
authors: V
authors: D'Almeida
authors: Miriam S
authors: MS
authors: Dolnikoff
authors: Cássia T
authors: CT
authors: Bergamaschi
authors: Ruy R
authors: RR
authors: Campos
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D000975:Antioxidants / Q000008:administration & dosage; D001205:Ascorbic Acid / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006339:Heart Rate; D006978:Hypertension, Renovascular / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D007262:Infusions, Intravenous; D007668:Kidney / Q000294:innervation; D008026:Ligation; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008845:Microinjections; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012077:Renal Artery / Q000601:surgery; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
chemical_list: D000959:Antihypertensive Agents; D000975:Antioxidants; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D017392:Thiobarbituric Acid Reactive Substances; D013482:Superoxide Dismutase; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D001205:Ascorbic Acid