NITRIC-OXIDE DECREASES LUNG INJURY AFTER INTESTINAL ISCHEMIA

After injury to a primary organ, mediators are released into the circu lation and may initiate inflammation of remote organs. We hypothesized that the local production of nitric oxide (NO) may act to limit the s pread of inflammation to secondarily targeted organs. In anesthetized rats, 30 min of intestinal ischemia followed by 2 h of reperfusion (I/ R) did not increase lung albumin leak. However, after treatment with N -G-nitro-L-arginine methyl ester (L-NAME), intestinal I/R led to incre ased lung leak, suggesting a protective effect of endogenous NO. The s ite of action of NO appeared to be the lung and not the gut because 1) after treatment with L-NAME, local delivery of NO to the lung by inha lation abolished the increase in intestinal I/R-induced lung leak; 2) L-NAME had no effect on epithelial permeability (Cr-15-labeled EDTA cl earance) of reperfused small bowel; and 3) after treatment with L-NAME , local delivery of NO to the gut by luminal perfusion did not improve epithelial permeability of reperfused intestines. Furthermore, L-NAME increased, and inhaled NO decreased, the density of lung neutrophils in rats subjected to intestinal I/R, and treatment with the selectin a ntagonist fucoidan abolished L-NAME-induced lung leak in rats subjecte d to intestinal I/R. We conclude that endogenous lung NO Limits second ary lung injury after intestinal I/R by decreasing pulmonary neutrophi l retention.