Endogenous nitric oxide synthesis and vascular leakage in ischemic-reperfused rabbit lungs.
Pulmonary edema formation resulting from loss of capillary barrier properties is a prominent finding in lung ischemia/reperfusion (I/R) injury. The role of endogenous nitric oxide (NO) in this process is unresolved. We exposed buffer-perfused rabbit lungs to warm I/R and measured air space NO liberation and intravascular accumulation of NO degradation products. In lungs undergoing 210 min of ischemia with normoxic ventilation, with maintenance of positive intravascular pressure to avoid vascular collapse, NO synthesis was moderately reduced during ischemia but was fully restored upon reperfusion, and a moderate leakage response occurred during reperfusion. Pretreatment with the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) suppressed NO synthesis but did not affect the leakage. During ischemia with anoxic ventilation, NO synthesis was fully abrogated, but again promptly reappeared upon reperfusion and entrance of oxygen into the system. It was with this protocol that the most severe vascular leakage was encountered, which was markedly reduced in the presence of L-NMMA or superoxide dismutase. We conclude that endogenous NO does not play a major role in the induction or mitigation of I/R injury under conditions of normoxic ischemia, but that return of endogenous NO synthesis upon reperfusion after anoxic ischemia contributes substantially to the triggering of vascular leakage, possibly via interaction with superoxide.
Schütte
H
H
Department of Internal Medicine, Justus-Liebig University, Giessen, Germany. hartwig.schuette@innere.med.uni-giessen.de
Mayer
K
K
Burger
H
H
Witzenrath
M
M
Gessler
T
T
Seeger
W
W
Grimminger
F
F
D000818:Animals; D046508:Culture Techniques; D008171:Lung Diseases / Q000503:physiopathology*; D009569:Nitric Oxide / Q000032:analysis* / Q000378:metabolism; D011654:Pulmonary Edema / Q000503:physiopathology*; D011817:Rabbits; D015427:Reperfusion Injury / Q000503:physiopathology*
D009569:Nitric Oxide