ENDOGENOUS NITRIC-OXIDE RELEASE MODULATES MURAL PLATELET THROMBOSIS AND NEUTROPHIL-ENDOTHELIUM INTERACTIONS UNDER LOW AND HIGH-SHEAR CONDITIONS

Nitric oxide (NO) plays an important role in the maintenance of a cons tant vasodilator tone in the vasculature and confers anti-adhesive pro perties to the normal functioning endothelium. Whether endogenous NO r elease influences platelet thrombus formation and neutrophil-endotheli um interactions under arterial blood flow conditions was investigated in ex vivo bioassay experiments using superfusion flow chambers. Surfa ces of intact or deeply injured porcine arterial segments were exposed to flowing porcine arterial blood under shear conditions typical to p atent (424 sec(-1)) and stenosed (3397 sec(-1)) arteries, at baseline and after administration of the specific inhibitor of NO synthesis N-o mega-nitro-L-arginine methyl ester (L-NAME, 3 mg/kg + 3 mg/kg/h; i.v.) . L-NAME induced a rapid and significant rise in arterial blood pressu re, with a moderate reduction in heart rate. Cr-51 platelet deposition on the exposed arterial media, which averaged 15.9+/-2.9 x 10(6)/cm(2 ) at a shear rate of 424 sec(-1), was increased by L-NAME, to 20.4+/-2 .8 x 10(6)/cm(2) (p <0.05). At 3397 sec(-1) of shear rate, platelet de position was higher (71.4+/-11.9 x 10(6)/cm(2)) (p <0.001), and was en hanced by 34%, to 95.8+/-12.5 x 10(6)/cm(2) (p <0.05), after L-NAME tr eatment. In-111 neutrophil adhesion to the vascular endothelium was al so increased by L-NAME by 83%, from 10.6+/-2.5 to 19.4+/-5.7 x 10(3)/c m(2) (p <0.05) at 424 sec(-1), and by 110%, from 14.1+/-4.3 to 29.7+/- 10.0 x 10(3)/cm(2) (p <0.05) at 3397 sec(-1) of shear rate. These resu lts suggest that endogenous NO may be an important modulator of thromb otic and inflammatory processes in patent as well as in stenosed arter ies. Copyright (C) 1997 Elsevier Science Ltd.