title: Oxidative stress and nitric oxide system in post-transplant hypertension.
abstract: BACKGROUND
  CsA-induced endothelial dysfunction and CsA-induced hypertension have been attributed to CsA effects on the endothelial-derived factors controlling vasomotor tone, but the mechanisms responsible are unclear. Endothelial nitric oxide (NO) is known to maintain a state of basal vasodilation and recently a NO mediated counterregulatory mechanism protective from CsA-induced vasoconstriction has been suggested.
  
  
  METHODS
  Our study evaluates ecNOS gene status and NO metabolites in kidney transplanted patients under chronic CsA treatment with CsA-induced hypertension. Since CsA increases superoxide production, which metabolizes NO, plasma hydroperoxides and peroxynitrite were also evaluated as index of the presence of "oxidative stress".
  
  
  RESULTS
  Quantification of monocyte ecNOS mRNA and NO metabolites plasma level from patients and control subjects (C) demonstrated NO system up regulation in patients notwithstanding hypertension. The mean ecNOS to beta-actin ratio was 2.00 +/- 0.87 vs 0.29 +/- 0.08 in C, p < 0.04. NO metabolite plasma level was 30.03 +/- 9.62 mM vs 9.37 +/- 3.86, p < 0.001. Hydroperoxides were also increased in patients: 3.6 +/- 1.6 i.a.u. vs 1.4 +/- 0.8, p < 0.007 (from cholesterol esters) and 10.8 +/- 6.6 vs 1.5 +/- 0.9, p < 0.008 (from triglycerides) as well as peroxynitrite plasma level: 0.36+/- 0.14 mM/L vs undetectable in C.
  
  
  CONCLUSIONS
  This study confirms a NO system up-regulation in transplanted patients. However, the counterregolatory system to CsA-induced vasoconstriction, could be cancelled by CsA induced superoxide and free radicals production which, increasing NO metabolism could contribute to CsA induced vasoconstriction and hypertension.
authors.affiliation: Department of Clinical and Experimental Medicine, Clinica Medica 4, University of Padova, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Calò
authors.forename: R
authors.initials: R
authors.lastname: Marcon
authors.forename: P
authors.initials: P
authors.lastname: Rigotti
authors.forename: E
authors.initials: E
authors.lastname: Pagnin
authors.forename: G
authors.initials: G
authors.lastname: Mennella
authors.forename: M
authors.initials: M
authors.lastname: Spinello
authors.forename: L
authors.initials: L
authors.lastname: Bonfante
authors.forename: S
authors.initials: S
authors.lastname: Cantaro
authors.forename: A
authors.initials: A
authors.lastname: D'Angelo
authors.forename: A
authors.initials: A
authors.lastname: Semplicini
authors.forename: A
authors.initials: A
authors.lastname: Antonello
mesh_terms: D006801:Humans; D006977:Hypertension, Renal / Q000209:etiology / Q000378:metabolism*; D016030:Kidney Transplantation / Q000009:adverse effects; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D019459:Urothelium / Q000378:metabolism
chemical_list: D009569:Nitric Oxide; D019001:Nitric Oxide Synthase