title: Introgression of the Brown Norway renin allele onto the Dahl salt-sensitive genetic background increases Cu/Zn SOD expression in cerebral arteries.
abstract: BACKGROUND
  Nitric oxide (NO)-dependent vasodilation is impaired in middle cerebral arteries (MCAs) from Dahl salt-sensitive (SS) rats that are fed normal salt (NS) diet, due to low plasma renin activity and chronic exposure to low plasma angiotensin II (ANG II) levels. NO-dependent vasodilator responses are rescued in MCAs from Ren1-BN congenic rats, which have a 2.0 Mbp portion of Brown Norway (BN) chromosome 13 containing the renin gene introgressed onto the Dahl SS genetic background.
  
  
  METHODS
  Vascular superoxide levels were measured with dihydroethidium (DHE) fluorescence in basilar arteries from 10- to 14-week-old, male Dahl SS and Ren1-BN congenic rats that fed NS diet. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and xanthine oxidase (XO) activity were also measured in cerebral artery tissue homogenates. Expression of the superoxide dismutase (SOD) enzymes was evaluated via western blotting in cerebral arteries from the two rat strains.
  
  
  RESULTS
  Superoxide levels were significantly higher in basilar arteries from Dahl SS rats compared to Ren1-BN congenic rats. NADPH oxidase and XO activity were similar between the two rat strains. Cu/Zn SOD expression was significantly higher in cerebral arteries from Ren1-BN congenic rats vs. those from Dahl SS rats. The expression of Mn-SOD was similar in cerebral arteries from both strains.
  
  
  CONCLUSIONS
  These findings suggest that introgressing the BN renin allele onto the Dahl SS genetic background to restore normal activity of the renin-angiotensin system (RAS) protects NO-dependent vascular relaxation in cerebral arteries by increasing the expression of Cu/Zn SOD and lowering vascular superoxide levels.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Durand
authors.forename: Julian H
authors.initials: JH
authors.lastname: Lombard
mesh_terms: D000483:Alleles; D000818:Animals; D002536:Cerebral Arteries / Q000201:enzymology*; D008297:Male; D019255:NADPH Oxidases / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D011914:Rats, Inbred BN; D020303:Rats, Inbred Dahl; D012083:Renin / Q000235:genetics*; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000502:physiology*; D013481:Superoxides / Q000097:blood; D014969:Xanthine Oxidase / Q000502:physiology
chemical_list: D013481:Superoxides; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D019255:NADPH Oxidases; D012083:Renin