title: Effects of chronic N-acetylcysteine treatment on the actions of peroxynitrite on aortic vascular reactivity in hypertensive rats.
abstract: BACKGROUND
  Peroxynitrite (ONOO-), the product of superoxide and nitric oxide, seems to be involved in vascular alterations in hypertension.
  
  
  OBJECTIVE
  To evaluate the effects of ONOO- on endothelium-dependent and independent aortic vascular responsiveness, oxidized/reduced glutathione balance (GSSG/GSH), malondialdehyde aortic content, and the formation of 3-nitrotyrosine (3-NT), a stable marker of ONOO-, in N-acetylcysteine (NAC)-treated normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR).
  
  
  RESULTS
  In SHR only, NAC significantly reduced heart rate and systolic, but not diastolic, blood pressure. It also improved endothelium-dependent aortic relaxation in SHR, but not after exposure to ONOO-. Endothelium-dependent and independent aortic relaxations were markedly impaired by ONOO- in both strains of rat. NAC partially protected SHR against the ONOO- -induced reduction in endothelium-independent relaxation. Aortic GSSG/GSH ratio and malondialdehyde, which were higher in SHR than in WKY rats, showed a greater increase in SHR after exposure to ONOO-. NAC decreased GSSG/GSH and malondialdehyde in both strains of rat before and after exposure to ONOO-. The 3-NT concentration, which was similar in both strains of rat under basal conditions, was greater in SHR than in WKY rats after the addition of ONOO-, with a reduction only in NAC-treated SHR.
  
  
  CONCLUSIONS
  These findings suggest an increased vulnerability of SHR aortas to the effects of ONOO- as compared with those of WKY rats. The selective improvements produced by NAC, in systolic arterial pressure, heart rate, aortic endothelial function, ONOO- -induced impairment of endothelium-independent relaxation, aortic GSSG/GSH balance, malondialdehyde content and 3-NT formation in SHR suggest that chronic administration of NAC may have a protective effect against aortic vascular dysfunction in the SHR model of hypertension.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Montreal, Québec, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Cabassi
authors.forename: E C
authors.initials: EC
authors.lastname: Dumont
authors.forename: H
authors.initials: H
authors.lastname: Girouard
authors.forename: J F
authors.initials: JF
authors.lastname: Bouchard
authors.forename: M
authors.initials: M
authors.lastname: Le Jossec
authors.forename: D
authors.initials: D
authors.lastname: Lamontagne
authors.forename: J G
authors.initials: JG
authors.lastname: Besner
authors.forename: J
authors.initials: J
authors.lastname: de Champlain
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology*; D004357:Drug Synergism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D016166:Free Radical Scavengers; D009566:Nitrates; D014665:Vasodilator Agents; D030421:Peroxynitrous Acid; D009599:Nitroprusside; D014443:Tyrosine; D008315:Malondialdehyde; D005978:Glutathione; D007545:Isoproterenol; D000109:Acetylcholine; D019803:Glutathione Disulfide; D000111:Acetylcysteine