Nitric oxide (endothelium-derived relaxing factor) attenuates revascularization-induced lung injury

Aortic occlusion and revascularization (I-R) may lead to lung injury dependant on activated neutrophil adherence. Nitric oxide (NO) inhibits neutrophil adherence to endothelial cells. We studied the effect of increasing or decreasing NO levels with sodium nitroprusside (SNP) or N -nitro-l-arginine methyl ester (L-NAME) in an I-R lung injury model of 30 min ischemia followed by 120 min reperfusion. Sprague-Dawley rats (10/group) were randomized to controls, I-R, I-R treated with l -NAME (10 mg/ml/hr), and I-R treated with SNP (0.2 mg/ml/hr). Myeloperoxidase activity (MPO) was used as a measure of pulmonary neutrophil influx. Pulmonary endothelial permeability was measured by wet:dry weight ratio and bronchoalveolar lavage protein (BAL prot) and neutrophil counts (BAL PMN). Aortic occlusion and revascularization led to significant increases in pulmonary neutrophil influx (6.1 ± 0.1 MPO u/g vs 3.05 ± 0.4 MPO u/g in the control group, P < 0.001) and microvascular leakage; BAL prot (347 ± 32 mg/ml in controls vs 454 ± 16 mg/ml in the I-R group, P < 0.05); and BAL PMN (0.7 ± 0.05 in controls vs 1.8 ± 0.07 PMN/ml in the I-R group, P < 0.001). These changes were exacerbated further by administration of l-NAME (MPO = 8.9 ± 0.7; BAL prot = 581 ± 40 mg/ml; BAL PMN = 2.7 ± 0.16 PMN/ml). Sodium nitroprusside therapy attenuated the I-R-induced lung injury (3.5 ± 0.4 MPO u/g, P < 0.05 vs I-R; BAL prot = 330 ± 61 mg/ml; BAL PMN = 0.9 ± 0.1 PMN/ml). These data suggest that NO in vivo inhibits I-R-induced lung injury, perhaps by inhibiting pulmonary neutrophil influx.