The nitric oxide synthase inhibitor N(G)-nitro-L-arginine decreases defibrillation-induced free radical generation.

Journal Article (Journal Article)

OBJECTIVES: To demonstrate that nitric oxide (NO) contributes to free radical generation after epicardial shocks and to determine the 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 (O(2).(-)) radical to form 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. METHODS AND 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 (Ascz.(-)), 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, Ascz.(-) rose 39+/-2.5% from baseline. After L-NNA infusion, a similar 40 J shock caused Ascz.(-) to increase only 2+/-3% from 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(-).

Full Text

Duke Authors

Cited Authors

  • Clark, CB; Zhang, Y; Martin, SM; Ray Davies, L; Xu, L; Kregel, KC; Miller, FJ; Buettner, GR; Kerber, RE

Published Date

  • April 2003

Published In

Volume / Issue

  • 57 / 1

Start / End Page

  • 101 - 108

PubMed ID

  • 12668306

International Standard Serial Number (ISSN)

  • 0300-9572

Digital Object Identifier (DOI)

  • 10.1016/s0300-9572(02)00413-6


  • eng

Conference Location

  • Ireland