title: Plasma dimethylarginines during the acute inflammatory response.
abstract: BACKGROUND
  Asymmetric dimethylarginine (ADMA) concentrations are increased in critically ill patients and may play a role in multiple organ failure. However, plasma ADMA concentrations during the development of the inflammatory response have not been documented. We measured plasma ADMA, as well as urinary excretion of its major metabolite dimethylamine, and nitrate as a marker of nitric oxide synthase (NOS) activity, in a cohort of patients undergoing elective knee arthroplasty that is known to provoke a significant inflammatory response.
  
  
  METHODS
  Thirty-eight patients were recruited. Fasting venous blood samples were obtained pre-operatively and at 12h and daily until the fifth post-operative day. ADMA and symmetric dimethylarginine (SDMA) were measured by high-performance liquid chromatography (HPLC). Urinary dimethylamine and nitrate were measured pre-operatively and on each of the post-operative mornings using HPLC and expressed as a ratio to creatinine.
  
  
  RESULTS
  Plasma ADMA fell by a median of 31% during the post-operative period, reaching a nadir on day 2, and recovering to baseline by the end of the study. SDMA showed no significant changes. No increase in urinary dimethylamine excretion was noted until day 5 post-op, whereupon it doubled. Urinary nitrate showed a small, but nonsignificant decrease on day 2, suggesting no major activation of NOS activity.
  
  
  CONCLUSIONS
  Plasma ADMA concentration decreases rapidly and transiently during the first 48h of acute inflammation. This appears not be caused by increased catabolism and may reflect increased cellular partitioning. This may serve to regulate NOS activity and prevent harmful increases in inducible NOS in situations where it is not appropriate.
authors.affiliation: Department of Clinical Biochemistry, Royal Infirmary, Glasgow, UK.
authors.forename: Scott
authors.initials: S
authors.lastname: Blackwell
authors.forename: Denis St J
authors.initials: DS
authors.lastname: O'Reilly
authors.forename: David
authors.initials: D
authors.lastname: Reid
authors.forename: Dinesh
authors.initials: D
authors.lastname: Talwar
mesh_terms: D000210:Acute-Phase Reaction / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D019645:Arthroplasty, Replacement, Knee; D015331:Cohort Studies; D004123:Dimethylamines / Q000652:urine; D004791:Enzyme Inhibitors / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D007719:Knee Joint / Q000502:physiology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000097:blood; D011183:Postoperative Complications / Q000378:metabolism
chemical_list: D004123:Dimethylamines; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine; C034516:dimethylamine; D019001:Nitric Oxide Synthase