ENDOTHELIUM-DERIVED NITRIC-OXIDE ATTENUATES NEUTROPHIL ADHESION TO ENDOTHELIUM UNDER ARTERIAL FLOW CONDITIONS

Nitric oxide (NO) synthesized from cultured endothelial cells inhibits platelet aggregation and adhesion to subendothelial extracellular mat rix and may contribute to the thromboresistance of the endothelium. NO has also been shown to inhibit neutrophil aggregation and adherence t o postcapillary venules. Whether NO derived from the intact endotheliu m of an arterial wall can influence platelet and neutrophil adhesion u nder whole-blood arterial flow conditions was evaluated in this study. Porcine aortic segments with intact endothelium were exposed to flowi ng porcine arterial blood for 5 minutes at a shear rate of 424 sec(-1) . Pretreatment of the endothelium with the physiological precursor of NO, L-arginine (2 mmol/L), reduced In-111-labeled neutrophil adhesion by 32% from 10.2+/-1.6 to 6.9+/-1.3 x 10(3)/cm(2) (P<.05), relative to control. This effect was reversed by the inhibitor of NO synthesis, N -omega-nitro-L-arginine methyl ester (L-NAME, 5 mmol/L) (8.2+/-3.0 ver sus 8.6+/-3.2 x 10(3)/cm(2) for control; P=NS). Pretreatment of the en dothelium with D-arginine (2 mmol/L) did not influence neutrophil adhe sion (8.7+/-2.0 versus 8.6+/-2.0 x 10(3)/cm(2) for control; P=NS). The intact endothelium, which is normally thromboresistant, shows a low b asal level of Cr-51 activity, corresponding to a platelet adhesion les s than 0.5x10(6)/cm(2), and this thromboresistance was not significant ly influenced by L-arginine. These results indicate that NO derived fr om an intact arterial endothelium under whole-blood arterial flow cond itions may be an important modulator of neutrophil interaction with th e intact endothelium.