title: The nitric oxide synthase inhibitor N(G)-nitro-L-arginine decreases defibrillation-induced free radical generation.
abstract: OBJECTIVE
  to demonstrate that nitric oxide (NO) contributes to free radical generation after epicardial shocks and to determinethe effect of a nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine (L-NNA), on free radical generation.
  
  
  BACKGROUND
  Free radicals are generated by direct current shocks for defibrillation. NO reacts with the superoxide (O2*-) radical to for peroxynitrite (O = NOO-), which is toxic and initiates additional free radical generation. The contribution of NO to free radical generation after defibrillation is not fully defined.
  
  
  RESULTS
  Fourteen open chest dogs were studied. In the initial eight dogs, 40 J damped sinusoidal monophasic epicardial shocks was administered. Using electron paramagnetic resonance, we monitored the coronary sinus concentration of ascorbate free radical (Asc*-), a measure of free radical generation (total oxidative flux). Epicardial shocks were repeated after L-NNA, 5 mg/kg IV. In six additional dogs, immunohistochemical staining was done to identify nitrotyrosine, a marker of reactive nitrogen species-mediated injury, in post-shock myocardial tissue. Three of these dogs received L-NNA pre-shock. After the initial 40 J shock, Asc*- rose 39 +/- 2.5% from baseline. After L-NNA infusion, a similar 40 J shock caused Asc*- to increase only 2 +/- 3% form baseline (P < 0.05, post-L-NNA shock versus initial shock). Nitrotyrosine staining was more prominent in control animals than dogs receiving L-NNA, suggesting prevention of O = NOO- formation.
  
  
  CONCLUSIONS
  NO contributes to free radical generation and nitrosative injury after epicardial shocks; NOS inhibitors decrease radical generation by inhibiting the production of O = NOO-.
authors.affiliation: The Cardiovascular Center, University of Iowa, Iowa City, 52242, USA.
authors.forename: Craig B
authors.initials: CB
authors.lastname: Clark
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Sean M
authors.initials: SM
authors.lastname: Martin
authors.forename: L Ray
authors.initials: LR
authors.lastname: Davies
authors.forename: Linjing
authors.initials: L
authors.lastname: Xu
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Kregel
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Miller
authors.forename: Garry R
authors.initials: GR
authors.lastname: Buettner
authors.forename: Richard E
authors.initials: RE
authors.lastname: Kerber
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D004285:Dogs; D004554:Electric Countershock; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism*; D006651:Histocytochemistry; D009206:Myocardium; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000008:administration & dosage / Q000494:pharmacology*; D030421:Peroxynitrous Acid / Q000096:biosynthesis; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives*
chemical_list: D004791:Enzyme Inhibitors; D005609:Free Radicals; D013481:Superoxides; D030421:Peroxynitrous Acid; D019335:Nitroarginine; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D001205:Ascorbic Acid