title: Excessive nitric oxide impairs wound collagen accumulation.
abstract: BACKGROUND
  Nitric oxide (NO) plays a major regulatory role in wound collagen synthesis. We hypothesized that this regulatory role is tightly controlled by the levels of NO in the wound environment and that supranormal wound NO generation impairs wound collagen accumulation.
  
  
  METHODS
  We used the model of turpentine-induced granuloma in male Sprague-Dawley rats as a sterile inflammatory stimulus generating large amounts of NO. In this environment, NO generation increased by 260%, whereas collagen deposition was significantly reduced by 38.5% (729.7 ± 81.5 versus 449.4 ± 76.3 μg hydroxyproline/100 mg sponge, P<0.05). Inhibition of NO synthase activity using 300 mM L-N6-(1-iminoethyl)-lysine, a highly potent and selective inhibitor of inducible NO synthase, significantly reduced NO elevation by 43.3% and increased wound collagen deposition by 37.3% (P<0.05). These effects occurred without any anti-inflammatory effects of L-N6-(1-iminoethyl)-lysine as assessed by the white blood cell counts and levels of interleukins 1 and 6.
  
  
  CONCLUSIONS
  The data show that high levels of NO within the wound environment significantly reduce wound collagen deposition. Inhibition of NO generation restores collagen levels to normal levels. The regulatory effects of NO on wound collagen appear to be highly correlated with the amount of NO generated.
authors.affiliation: Department of Surgery, Sinai Hospital of Baltimore, Baltimore, Maryland, USA.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Park
authors.forename: Morton J
authors.initials: MJ
authors.lastname: Abrams
authors.forename: Philip A
authors.initials: PA
authors.lastname: Efron
authors.forename: Adrian
authors.initials: A
authors.lastname: Barbul
mesh_terms: D000818:Animals; D003094:Collagen / Q000096:biosynthesis*; D004353:Drug Evaluation, Preclinical; D006099:Granuloma / Q000139:chemically induced / Q000188:drug therapy; D007509:Irritants; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014425:Turpentine; D014945:Wound Healing; D014947:Wounds and Injuries / Q000139:chemically induced / Q000188:drug therapy
chemical_list: D007509:Irritants; C090663:N(6)-(1-iminoethyl)lysine; D009569:Nitric Oxide; D003094:Collagen; D019001:Nitric Oxide Synthase; D008239:Lysine; D014425:Turpentine