title: Renal nitric oxide synthase and antioxidant preservation in Cyp1a1-Ren-2 transgenic rats with inducible malignant hypertension.
abstract: BACKGROUND
  Dietary administration of 0.30% indole-3-carbinol (I3C) to Cyp1a1-Ren2 transgenic rats (TGRs) generates angiotensin II (ANG II)-dependent malignant hypertension (HTN) and increased renal vascular resistance. However, TGRs with HTN maintain a normal or slightly reduced glomerular filtration rate. We tested the hypothesis that maintenance of renal function in hypertensive Cyp1a1-Ren2 TGRs is due to preservation of the intrarenal nitric oxide (NO) and antioxidant systems.
  
  
  METHODS
  Kidney cortex, kidney medulla, aortic endothelial (e) and neuronal (n) nitric oxide synthase (NOS), superoxide dismutases (SODs), and p22phox (nicotinamide adenine dinucleotide phosphate-oxidase subunit) protein abundances were measured along with kidney cortex total antioxidant capacity (TAC) and NOx. TGRs were fed a normal diet that contained 0.3% I3C or 0.3% I3C + candesartan (AT1 receptor antagonist; 25mg/L in drinking water) (n = 5-6 per group) for 10 days.
  
  
  RESULTS
  Blood pressure increased and body weight decreased in I3C-induced TGRs, while candesartan blunted these responses. Abundances of NOS, SOD, and p22phox as well as TAC were maintained in the kidney cortex of I3C-induced TGRs with and without candesartan, while kidney cortex NOx production increased in both groups. Kidney medulla eNOS and extracellular (EC) SOD decreased and nNOS were unchanged in both groups of I3C-induced TGRs. In addition, a compensatory increase occurred in kidney medulla Mn SOD in I3C-induced TGRs + candesartan. Aortic eNOS and nNOS∝ fell and p22phox and Mn SOD increased in hypertensive I3C-induced TGRs; all changes were reversed with candesartan.
  
  
  CONCLUSIONS
  The preservation of renal cortical NO and antioxidant capacity is associated with preserved renal function in Cyp1a1-Ren2 TGRs with ANG II-dependent malignant HTN.
authors.affiliation: Departments of Physiology and Medicine, University of Florida, Gainesville, Florida.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Cunningham
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Sasser
authors.forename: Crystal A
authors.initials: CA
authors.lastname: West
authors.forename: Carlo J
authors.initials: CJ
authors.lastname: Milani
authors.forename: Chris
authors.initials: C
authors.lastname: Baylis
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001562:Benzimidazoles / Q000627:therapeutic use; D001713:Biphenyl Compounds; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D005919:Glomerular Filtration Rate; D006974:Hypertension, Malignant / Q000139:chemically induced / Q000503:physiopathology*; D007211:Indoles; D007668:Kidney / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D051381:Rats; D055647:Rats, Transgenic; D013777:Tetrazoles / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007211:Indoles; D013777:Tetrazoles; C016517:indole-3-carbinol; D052248:Nitric Oxide Synthase Type I; D019363:Cytochrome P-450 CYP1A1; D019255:NADPH Oxidases; C515768:Cyba protein, rat; C081643:candesartan
keywords: angiotensin receptor blocker; aorta; blood pressure; candesartan; hypertension; kidney; superoxide dismutase; total antioxidant capacity.