Role of nitric oxide in lung injury associated with experimental acute pancreatitis

Abstract

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 μg/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) μg/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) μg/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) μg/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.