title: 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 micrograms/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) micrograms/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) micrograms/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) micrograms/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.
authors.affiliation: Department of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin.
authors.forename: D A
authors.initials: DA
authors.lastname: O'Donovan
authors.forename: C J
authors.initials: CJ
authors.lastname: Kelly
authors.forename: H
authors.initials: H
authors.lastname: Abdih
authors.forename: D
authors.initials: D
authors.lastname: Bouchier-Hayes
authors.forename: R W
authors.initials: RW
authors.lastname: Watson
authors.forename: H P
authors.initials: HP
authors.lastname: Redmond
authors.forename: P E
authors.initials: PE
authors.lastname: Burke
authors.forename: D A
authors.initials: DA
authors.lastname: Bouchier-Hayes
mesh_terms: D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000201:enzymology / Q000209:etiology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D009929:Organ Size; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications* / Q000201:enzymology; D009195:Peroxidase / Q000378:metabolism; D011506:Proteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011506:Proteins; D009569:Nitric Oxide; D009195:Peroxidase