ROLE OF NITRIC-OXIDE IN LUNG INJURY ASSOCIATED WITH EXPERIMENTAL ACUTE-PANCREATITIS

This study evaluated the effect of varying the synthesis of nitric oxi de with sodium nitroprusside or N-nitro-L-arginine methyl ester (L-NAM E) in a pancreatitis-lung injury model. Rats (n = 45) were randomized to control or caerulein-induced pancreatitis groups, treated with sali ne, sodium nitroprusside (0.4 mu g/kg) or L-NAME (10 mg/kg). Myelopero xidase activity was used as a measure of neutrophil infiltration. Wet to dry (W:D) lung weight and bronchoalveolar lavage (BAL) protein conc entrations were used to assess vascular leakage. Pancreatitis was show n to induce pulmonary neutrophil influx: mean(s.e.m.) myeloperoxidase activity 6.79(0.5) units/g in caerulein-treated animals versus 2.08(0. 5) units/g in controls (P<0.001). Animals with pancreatitis showed inc reased microvascular leakage compared with controls (mean(s.e.m.) W:D lung weight 7.01(0.5) versus 2 85(0.2), P(0.001; BAL protein concentra tion 2539(222) versus 347(32)mu g/ml, P<0.001). Compared with the sali ne-treated pancreatitis group, these changes were reduced by sodium ni troprusside (mean(s.e.m.) myeloperoxidase activity to 2.5(0.4) units/g , P<0.001; W:D lung weight to 3.8(0.37), P(0.001; BAL protein concentr ation 1389(182)mu g/ml, P<0.05). L-NAME exacerbated the pancreatitis-i nduced pulmonary oedema (W:D lung weight increased to 11.96(0.6), P<0. 001), protein leakage (BAL protein concentration rose to 3707(309)mu g /ml, P<0.05) and neutrophil infiltration (myeloperoxidase activity inc reased to 9.01(0.3) units/g, P(0.05). These data suggest that, in vivo , nitric oxide inhibits pancreatitis-induced lung injury, possibly in part by inhibiting pulmonary neutrophil influx.