title: Effect of ischemia-reperfusion on renal expression and activity of N(G)-N(G)-dimethylarginine dimethylaminohydrolases.
abstract: BACKGROUND
  Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. It is degraded by the enzyme dimethylarginine dimethylaminohydrolase (DDAH).
  
  
  METHODS
  Rats (n = 50) underwent to 45 min of renal ischemia followed by 30 min, 1 h, and 3 h of reperfusion. Expression of endothelial nitric oxide synthase, inducible nitric oxide synthase, DDAH-1, DDAH-2, renal DDAH activity, plasma NO2(-)/NO3(-), and ADMA levels were evaluated.
  
  
  RESULTS
  Inducible nitric oxide synthase expression increased, as confirmed by both plasma (11.89 +/- 1.02, 15.56 +/- 0.93, 11.82 +/- 0.86, 35.05 +/- 1.28, and 43.89 +/- 1.63 nmol/ml in the control, ischemic, 30-min, 1-h, and 3-h groups, respectively) and renal (4.81 +/- 0.4, 4.85 +/- 1, 9.42 +/- 0.7, 15.42 +/- 0.85, and 22.03 +/- 1.11 nmol/mg protein) formations of NO2(-)/NO3(-). DDAH-1 expression decreased after reperfusion, whereas DDAH-2 increased after 30 min, returning to basal levels after 3 h. Total DDAH activity was reduced during all times of reperfusion. Both plasma (0.41 +/- 0.03, 0.43 +/- 0.05, 0.62 +/- 0.02, 0.71 +/- 0.02, and 0.41 +/- 0.01 nmol/ml in the control, ischemic, 30-min, 1-h, and 3-h groups, respectively) and renal (1.51 +/- 0.01, 1.5 +/- 0.01, 1.53 +/- 0.01, 2.52 +/- 0.04, and 4.48 +/- 0.03 nmol/mg protein in the control, ischemic, 30-min, 1-h, and 3-h groups, respectively) concentrations of ADMA increased.
  
  
  CONCLUSIONS
  Results suggest that ischemia-reperfusion injury leads to reduced DDAH activity and modification of different DDAH isoform expression, thus leading to increased ADMA levels, which may lead to increased cardiovascular risk.
authors.affiliation: Department of Biological Chemistry, Medical Chemistry and Molecular Biology, University of Catania, Italy. livolti@unict.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Li Volti
authors.forename: Valeria
authors.initials: V
authors.lastname: Sorrenti
authors.forename: Rosaria
authors.initials: R
authors.lastname: Acquaviva
authors.forename: Paolo
authors.initials: P
authors.lastname: Murabito
authors.forename: Antonino
authors.initials: A
authors.lastname: Gullo
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Barcellona
authors.forename: Fabio
authors.initials: F
authors.lastname: Galvano
authors.forename: Luigi
authors.initials: L
authors.lastname: Rodella
authors.forename: Rita
authors.initials: R
authors.lastname: Rezzani
authors.forename: Luca
authors.initials: L
authors.lastname: Vanella
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tringali
authors.forename: Massimo
authors.initials: M
authors.lastname: Caruso
authors.forename: Diego
authors.initials: D
authors.lastname: Gazzolo
authors.forename: Claudia
authors.initials: C
authors.lastname: Di Giacomo
mesh_terms: D000581:Amidohydrolases / Q000096:biosynthesis*; D000818:Animals; D004789:Enzyme Activation / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D007511:Ischemia / Q000201:enzymology* / Q000473:pathology; D007668:Kidney / Q000098:blood supply* / Q000201:enzymology* / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D015424:Reperfusion
chemical_list: D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D000581:Amidohydrolases; C059999:dimethylargininase