title: Impairment of vascular responses to reactive hyperemia and nitric oxide in chronic renal failure.
abstract: BACKGROUND
  Cardiovascular events are the leading cause of morbidity and mortality in patients with end-stage renal disease. The role of endothelial dysfunction, an early marker of arteriosclerosis, in patients with chronic renal failure (CRF) before the initiation of maintenance hemodialysis (HD), and the factors affecting endothelial dysfunction in the setting of chronic renal failure remain poorly understood.
  
  
  METHODS
  We evaluated endothelial function by measuring flow-mediated vasodilation (%FMD) during reactive hyperemia in healthy individuals (HCS) and patients with chronic renal failure with (HD) or without (ND) hemodialysis. Nonspecific endothelium-independent vasodilation (%NTG) was measured after the administration of sublingual glyceryl trinitrate spray (0.3 mg). Factors affecting %FMD and %NTG were also tested.
  
  
  RESULTS
  In ND and HD, plasma homocysteine, cysteine and stable NO metabolite (NO(-)(3)) concentrations were significantly elevated. In ND and HD, reactive hyperemia as well as %NTG and %FMD were attenuated to a similar degree. On multivariate regression analysis, NO(-)(3) concentration was directly correlated with both %FMD and %NTG, while the glutathione (GSH) concentration correlated with only %NTG.
  
  
  CONCLUSIONS
  Our findings indicate that chronic renal failure before the initiation of maintenance hemodialysis impairs endothelial function and/or the response to NO, which is accompanied by the attenuated reactive hyperemia. Furthermore, the impairment might be related to the decreased synthesis or the dissipation of NO.
authors.affiliation: Department of Kidney and Dialysis, Hyogo College of Medicine, Nishinomiya, Japan. t-nkns@hyo-med.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ishigami
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Otaki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Izumi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hiraoka
authors.forename: Toru
authors.initials: T
authors.lastname: Inoue
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takamitsu
mesh_terms: D001794:Blood Pressure / Q000502:physiology; D003404:Creatinine / Q000097:blood; D003545:Cysteine / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000097:blood; D006710:Homocysteine / Q000097:blood; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood*; D005996:Nitroglycerin / Q000008:administration & dosage; D012039:Regional Blood Flow / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D009566:Nitrates; D014665:Vasodilator Agents; D006710:Homocysteine; D009569:Nitric Oxide; D003404:Creatinine; D005996:Nitroglycerin; D005978:Glutathione; D003545:Cysteine