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.

Relative Contribution of Hemopoietic and Pulmonary Parenchymal Cells to Lung Inducible Nitric Oxide Synthase (iNOS) Activity in Murine Endotoxemia

“…Thus, NO pro- duced by the endothelium may attenuate neutrophil adhesion in the microvasculature (15,16). Further, NO may modulate apoptosis of neutrophils, and hence neutrophil survival in inflammatory lung injury.…”

Expression of Nitric Oxide Synthase Isoforms and Nitric Oxide Production in Acute Pancreatitis and Associated Lung Injury

“…Alveolar macrophages have the capacity to mobilize large numbers of leukocytes and secrete cytokines, arachidonic acid metabolites and NO [47] . Studies also showed that NO diminishes the pulmonary injury associated with AP and that the decrease in pulmonary injury is associated with diminished neutrophil infiltration [48] . A previous study showed a greater protection in lungs as compared to the pancreas in a PPTA deletion model of AP [45] .…”

A Novel Therapeutic Strategy for Attenuating Neutrophil-Mediated Lung Injury In Vivo

“…11 The right ventricle was cannulated with a 25-gauge needle and the right pulmonary hilum was clamped. The pulmonary vasculature of the left lung was flushed with 50 mL PBS to clear the lung of intravascular PMNs.…”