NITRIC-OXIDE MEDIATES ACUTE LUNG INJURY BY MODULATION OF INFLAMMATION

Nitric Oxide's (NO) function in vasomotor control, inflammation, and s ignal transduction makes it an attractive potential mediator of the ca pillary leak seen in acute lung injury. Despite extensive study, the r ole of NO in intestinal ischemia/reperfusion-induced capillary leak re mains controversial, Rats were treated with vehicle, norepinephrine, o r L-NNA (nitric oxide synthase inhibitor) and then underwent sham lapa rotomy or 30 min SMA occlusion followed by 1 to 12 h of reperfusion. E van's Blue dye was administered 1 h before animals were euthanized. Ra tios of bronchoalveolar lavage or small-intestine lavage to serum dye concentrations were calculated as measures of capillary leak. Circulat ing neutrophil activation was measured with a nitroblue tetrazolium re duction assay. In vehicle-treated animals, both capillary leakage and PMN activation peaked at 4 h of reperfusion. These parameters returned to baseline by 12 h, Treatment with L-NNA accelerated ischemia/reperf usion-induced PMN activation as well as accelerated capillary leak fro m 4 to 1 h, Treatment with norepinephrine (hypertensive control) incre ased the magnitude of lung capillary leak but had no effect on the tim ing of ischemia/reperfusion-induced PMN activation or ischemia/reperfu sion-induced capillary leak. These data show that intestinal ischemia/ reperfusion-induced systemic capillary leak is associated with systemi c neutrophil activation, Nitric oxide synthase inhibition accelerates ischemia/reperfusion-induced capillary leak and mediates the capillary leak seen in acute lung injury by modulating neutrophil activation. ( C) 1998 Academic Press.