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

This study evaluated the effect of varying the synthesis of nitric oxide with sodium nitroprusside or N-nitro-L-arginine methyl ester (L-NAME) in a pancreatitis-lung injury model. Rats (n = 45) were randomized to control or caerulein-induced pancreatitis groups, treated with saline, sodium nitroprusside (0.4 mu g/kg) or L-NAME (10 mg/kg). Myeloperoxidase activity was used as a measure of neutrophil infiltration. Wet to dry (W:D) lung weight and bronchoalveolar lavage (BAL) protein concentrations were used to assess vascular leakage. Pancreatitis was shown 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 increased 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 concentration 2539(222) versus 347(32)mu g/ml, P<0.001). Compared with the saline-treated pancreatitis group, these changes were reduced by sodium nitroprusside (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 concentration 1389(182)mu g/ml, P<0.05). L-NAME exacerbated the pancreatitis-induced 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 increased 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.