title: Nitrosoglutathione modulation of platelet activation and nitric oxide synthase expression in promotion of flap survival after ischemia/reperfusion injury.
abstract: BACKGROUND
  Recent studies have shown that platelets play an important role in the pathogenesis of reperfusion injury. Using an inferior epigastric artery skin flap as a flap ischemia/reperfusion (I/R) injury model, we investigated whether the administration of a nitric oxide (NO) donor, nitrosoglutathione (GSNO), could decrease platelet activation and modulate the NO synthase (NOS) activity of platelets and promote flap survival.
  
  
  METHODS
  Thirty minutes before flap reperfusion, normal saline (1 mL), nitrosoglutathione (GSNO 0.2, 0.6, 3 mg/kg), or N(G)-nitro-L-arginine-methyl ester (450 mg/kg) was injected intravenously in 10 rats, respectively. The p-selectin (CD62P) expression of platelet activation was detected by a flow cytometry. Immunohistochemical staining was performed to investigate the CD62P deposition on the microvasculature of the flap vessels. NOS isoform expression in the platelets was evaluated by Western blot. Tissue perfusion was monitored by using laser-Doppler flowmetry. Survival areas were assessed at 7 days postoperatively
  
  
  RESULTS
  An optimal dose of GSNO (0.6 mg/kg), significantly decreased in CD62P expression on platelets (P < 0.001) and its deposition on the flap vessels, selectively suppressed iNOS induction of platelet, and significantly improved blood perfusion and the flap survival rate (59.8 +/- 4.9% versus 22.1 +/- 6.1%, P < 0.001). In contrast, the NO synthase inhibitor, N(G)-nitro-l-arginine methyl ester, although inhibiting iNOS expression of platelets, compromised platelet activation, tissue perfusion, and flap survival.
  
  
  CONCLUSIONS
  This study suggests that GSNO can appropriately donate NO to suppress platelet activation and platelet iNOS induction, resulting in less platelet activation, better blood perfusion, and flap survival after I/R injury.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Yur-Ren
authors.initials: YR
authors.lastname: Kuo
authors.forename: Feng-Sheng
authors.initials: FS
authors.lastname: Wang
authors.forename: Seng-Feng
authors.initials: SF
authors.lastname: Jeng
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Huang
authors.forename: Fu-Chan
authors.initials: FC
authors.lastname: Wei
authors.forename: Kuender D
authors.initials: KD
authors.lastname: Yang
mesh_terms: D000818:Animals; D001158:Arteries / Q000601:surgery; D001792:Blood Platelets / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D019001:Nitric Oxide Synthase / Q000097:blood / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D019007:P-Selectin / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew; D012039:Regional Blood Flow / Q000187:drug effects; D015427:Reperfusion Injury / Q000097:blood / Q000201:enzymology / Q000503:physiopathology*; D026422:S-Nitrosoglutathione / Q000008:administration & dosage / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply* / Q000201:enzymology*; D013524:Surgical Flaps; D014022:Tissue Survival / Q000187:drug effects
chemical_list: D019007:P-Selectin; D026422:S-Nitrosoglutathione; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat