title: S-nitroso human serum albumin treatment reduces ischemia/reperfusion injury in skeletal muscle via nitric oxide release.
abstract: BACKGROUND
  Peroxynitrite generated from nitric oxide (NO) and superoxide (O2-) contributes to ischemia/reperfusion (I/R) injury. Feedback inhibition of endothelial NO synthase by NO may inhibit O2- production generated also by endothelial NO synthase at diminished local L-arginine concentrations accompanying I/R.
  
  
  RESULTS
  During hindlimb I/R (2.5 hours/2 hours), in vivo NO was monitored continuously (porphyrinic sensor), and high-energy phosphates, reduced and oxidized glutathione (chromatography), and I/R injury were measured intermittently. Rabbits receiving human serum albumin (HSA) (controls) were compared with those receiving S-nitroso human serum albumin (S-NO-HSA) beginning 30 minutes before reperfusion for 1 hour or 30 minutes before ischemia for 3.5 hours (0.1 micromol x kg(-1) x h(- 1)). The onset of ischemia led to a rapid increase of NO from its basal level (50+/-12 nmol/L) to 120+/-20 and 220+/-15 nmol/L in the control and S-NO-HSA-treated groups, respectively. In control animals, NO dropped below basal levels at the end of ischemia and to undetectable levels (<1 nmol/L) during reperfusion. In S-NO-HSA-treated animals, maximal NO levels never decreased below basal concentration and on reperfusion were 100+/-15 nmol/L (S-NO-HSA preischemia group, 175+/-15 nmol/L). NO supplementation by S-NO-HSA led to partial and in the preischemia group to total preservation of high-energy phosphates and glutathione status in reperfused muscle (eg, preischemia groups: ATP, 30.23+/-5.02 micromol/g versus control, 15.75+/-4.33 micromol/g, P<0.0005; % oxidized glutathione, 4.49+/- 1.87% versus control, 22.84+/-6.39%, P<0.0001). S-NO-HSA treatment in all groups led to protection from vasoconstriction and reduced edema formation after reperfusion (eg, preischemia groups: interfiber area, 12.94+/-1.36% versus control, 27.83+/-1.95%, P< 0.00001).
  
  
  CONCLUSIONS
  Long-lasting release of NO by S-NO-HSA provides significant protection of skeletal muscle from I/R injury.
authors.affiliation: Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701-2970, USA.
authors.forename: Seth
authors.initials: S
authors.lastname: Hallström
authors.forename: Harald
authors.initials: H
authors.lastname: Gasser
authors.forename: Christoph
authors.initials: C
authors.lastname: Neumayer
authors.forename: Alexander
authors.initials: A
authors.lastname: Fügl
authors.forename: Joseph
authors.initials: J
authors.lastname: Nanobashvili
authors.forename: Andrzej
authors.initials: A
authors.lastname: Jakubowski
authors.forename: Ihor
authors.initials: I
authors.lastname: Huk
authors.forename: Günther
authors.initials: G
authors.lastname: Schlag
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Malinski
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D002196:Capillaries / Q000473:pathology; D005978:Glutathione / Q000032:analysis; D006614:Hindlimb / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis*; D009603:Nitroso Compounds; D010725:Phosphocreatine / Q000032:analysis; D011817:Rabbits; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012710:Serum Albumin, Bovine / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D009603:Nitroso Compounds; C091665:S-nitrosoalbumin; D010725:Phosphocreatine; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D005978:Glutathione