Endogenous nitric oxide synthesis and vascular leakage in ischemic-reperfused rabbit lungs

Pulmonary edema formation resulting from loss of capillary barrier properti es is a prominent finding in lung ischemia/reperfusion (I/R) injury. The ro le of endogenous nitric oxide (NO) in this process is unresolved. We expose d buffer-perfused rabbit lungs to warm I/R and measured air space NO libera tion and intravascular accumulation of NO degradation products. In lungs un dergoing 210 min of ischemia with normoxic ventilation, with maintenance of positive intravascular pressure to avoid vascular collapse, NO synthesis w as moderately reduced during ischemia but was fully restored upon reperfusi on, and a moderate leakage response occurred during reperfusion. Pretreatme nt with the NO synthase inhibitor N-G-monomethyl-L-arginine (L-NMMA) suppre ssed NO synthesis but did not affect the leakage. During ischemia with anox ic ventilation, NO synthesis was fully abrogated, but again promptly reappe ared upon reperfusion and entrance of oxygen into the system. It was with t his protocol that the most severe vascular leakage was encountered, which w as markedly reduced in the presence Of L-NMMA or superoxide dismutase. We c onclude that endogenous NO does not play a major role in the induction or m itigation of I/R injury under conditions of normoxic ischemia, but that ret urn of endogenous NO synthesis upon reperfusion after anoxic ischemia contr ibutes substantially to the triggering of vascular leakage, possibly via in teraction with superoxide.