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 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.
O'Donovan
D A
DA
Department of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin.
Kelly
C J
CJ
Abdih
H
H
Bouchier-Hayes
D
D
Watson
R W
RW
Redmond
H P
HP
Burke
P E
PE
Bouchier-Hayes
D A
DA
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
D011506:Proteins; D009569:Nitric Oxide; D009195:Peroxidase