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 matrix and may contribute to the thromboresistance of the endothelium. NO has also been shown to inhibit neutrophil aggregation and adherence to postcapillary venules. Whether NO derived from the intact endothelium of an arterial wall can influence platelet and neutrophil adhesion under whole-blood arterial flow conditions was evaluated in this study. Porcine aortic segments with intact endothelium were exposed to flowing 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 111In-labeled neutrophil adhesion by 32% from 10.2 +/- 1.6 to 6.9 +/- 1.3 x 10(3)/cm2 (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 versus 8.6 +/- 3.2 x 10(3)/cm2 for control; P = NS). Pretreatment of the endothelium with D-arginine (2 mmol/L) did not influence neutrophil adhesion (8.7 +/- 2.0 versus 8.6 +/- 2.0 x 10(3)/cm2 for control; P = NS). The intact endothelium, which is normally thromboresistant, shows a low basal level of 51Cr activity, corresponding to a platelet adhesion less than 0.5 x 10(6)/cm2, and this thromboresistance was not significantly influenced by L-arginine. These results indicate that NO derived from an intact arterial endothelium under whole-blood arterial flow conditions may be an important modulator of neutrophil interaction with the intact endothelium.
Provost
P
P
Thrombosis and Atherosclerosis Laboratory, Montreal Heart Institute, Quebec, Canada.
Lam
J Y
JY
Lacoste
L
L
Merhi
Y
Y
Waters
D
D
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009504:Neutrophils / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D013552:Swine
D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester