NITRIC-OXIDE (ENDOTHELIUM-DERIVED RELAXING FACTOR) ATTENUATES REVASCULARIZATION-INDUCED LUNG INJURY

Aortic occlusion and revascularizaton (I-R) may lead to lung injury de pendant on activated neutrophil adherence. Nitric oxide (NO) inhibits neutrophil adherence to endothelial cells. We studied the effect of in creasing 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 (1 0 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. P ulmonary 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 in creases 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 leaka ge; 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 exacerba ted 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 nitroprussid e 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 P MN/ml). These data suggest that NO in vivo inhibits I-R-induced lung i njury, perhaps by inhibiting pulmonary neutrophil influx. (C) 1994 Aca demic Press, Inc.