title: Chronic inhibition of nitric oxide synthesis in rats increases aortic superoxide anion production via the action of angiotensin II.
abstract: OBJECTIVE
  Chronic inhibition of nitric oxide (NO) synthesis by Nomega-nitro-L-arginine methyl ester (L-NAME) increases vascular tissue angiotensin II activity and oxidative stress in animals by incompletely understood mechanisms. In a rat model, we investigated the role of local angiotensin II activity in the pathogenesis of increased oxidative stress.
  
  
  METHODS
  We studied the aortas of control rats and others receiving L-NAME or L-NAME plus an angiotensin II type 1 receptor antagonist (CS-866).
  
  
  RESULTS
  Administration of L-NAME for 7 days significantly increased superoxide anion (O2-) and both immunoreactivity and electrophoretically demonstrable activity of redox-sensitive transcription factors (NF-kappaB and AP-1). Treatment with the angiotensin II type 1 receptor antagonist prevented all of the above changes. The observed effects of the type 1 receptor antagonist was independent of the L-NAME-induced arterial hypertension.
  
  
  CONCLUSIONS
  These findings suggest that chronic inhibition of NO synthesis may increase vascular oxidative stress and oxidative stress-sensitive signals via the action of angiotensin II mediated via type 1 receptors.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University School of Medicine, Fukuoka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kitamoto
authors.forename: K
authors.initials: K
authors.lastname: Egashira
authors.forename: C
authors.initials: C
authors.lastname: Kataoka
authors.forename: M
authors.initials: M
authors.lastname: Usui
authors.forename: M
authors.initials: M
authors.lastname: Koyanagi
authors.forename: M
authors.initials: M
authors.lastname: Takemoto
authors.forename: A
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001013:Aorta, Thoracic / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D000068557:Olmesartan Medoxomil; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013481:Superoxides / Q000378:metabolism*; D013599:Systole / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D057911:Angiotensin Receptor Antagonists; D004791:Enzyme Inhibitors; D007093:Imidazoles; D016328:NF-kappa B; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D018808:Transcription Factor AP-1; D013481:Superoxides; D000804:Angiotensin II; D009569:Nitric Oxide; D000068557:Olmesartan Medoxomil; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester