AJP - Lung Cellular and Molecular Physiology, Vol 269, Issue 2 158-L164, Copyright © 1995 by American Physiological Society
Reactive species in ischemic rat lung injury: contribution of peroxynitrite
H. Ischiropoulos, A. B. al-Mehdi and A. B. Fisher
Institute for Environmental Medicine, School of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Lung ischemia-reperfusion represents a potentially important mechanism for
diverse forms of tissue injury associated with decreased pulmonary flow.
Previous studies demonstrated oxidative injury in ischemic-reperfused
lungs. The present study was designed to evaluate the contribution of
nitric oxide and peroxynitrite in tissue injury. The levels of the stable
decomposition products of nitric oxide and peroxynitrite, nitrite plus
nitrate, were twofold greater than control during reperfusion after 60 min
of ischemia. Inhibition of nitric oxide synthesis by endotracheal
insufflation of 5 mM NG-nitro-L-arginine methyl ester, 30 min before the
induction of ischemia, decreased the production of lung thiobarbituric acid
reactive substances (TBARS) by 67% (P < 0.05, n = 5), TBARS released
into the lung perfusate by 55% (P < 0.05, n = 5), lung-conjugated dienes
by 61% (P < 0.05, n = 5), and dinitrophenylhydrazine-reactive protein
carbonyl levels by 86% (P < 0.05, n = 5). Amino acid analysis of tissue
homogenates from lungs exposed to 60 min of ischemia and 60 min of
reperfusion revealed a 1.8-fold (P < 0.05, n = 5) increase in
nitrotyrosine concentration compared with 2 h continuously perfused lungs.
Inhibition of nitric oxide synthesis abolished the increase in
nitrotyrosine levels. Furthermore, lungs exposed to 60 min of reperfusion
after 60 min of ischemia showed specific binding of an anti-nitrotyrosine
antibody. In reperfused tissues, antibody binding was observed throughout
the lung. The binding was blocked with excess of nitrotyrosine, and minimal
binding was observed in nonperfused blood-free control lungs.(ABSTRACT
TRUNCATED AT 250 WORDS)
