Nitric oxide mediates acute lung injury by modulation of inflammation.
Nitric Oxide's (NO) function in vasomotor control, inflammation, and signal transduction makes it an attractive potential mediator of the capillary leak seen in acute lung injury. Despite extensive study, the role of NO in intestinal ischemia/reperfusion-induced capillary leak remains controversial. Rats were treated with vehicle, norepinephrine, or L-NNA (nitric oxide synthase inhibitor) and then underwent sham laparotomy or 30 min SMA occlusion followed by 1 to 12 h of reperfusion. Evan's Blue dye was administered 1 h before animals were euthanized. Ratios of bronchoalveolar lavage or small-intestine lavage to serum dye concentrations were calculated as measures of capillary leak. Circulating neutrophil activation was measured with a nitroblue tetrazolium reduction 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/reperfusion-induced PMN activation as well as accelerated capillary leak from 4 to 1 h. Treatment with norepinephrine (hypertensive control) increased the magnitude of lung capillary leak but had no effect on the timing of ischemia/reperfusion-induced PMN activation or ischemia/reperfusion-induced capillary leak. These data show that intestinal ischemia/reperfusion-induced systemic capillary leak is associated with systemic 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.
Tavaf-Motamen
H
H
Department of Surgery, Walter Reed Army Medical Center, Washington, DC, USA.
Miner
T J
TJ
Starnes
B W
BW
Shea-Donohue
T
T
D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002196:Capillaries / Q000201:enzymology / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D018375:Neutrophil Activation / Q000276:immunology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011652:Pulmonary Circulation; D011654:Pulmonary Edema / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000276:immunology* / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D009638:Norepinephrine