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 constant vasodilator tone in the vasculature and confers anti-adhesive properties to the normal functioning endothelium. Whether endogenous NO release influences platelet thrombus formation and neutrophil-endothelium interactions under arterial blood flow conditions was investigated in ex vivo bioassay experiments using superfusion flow chambers. Surfaces of intact or deeply injured porcine arterial segments were exposed to flowing porcine arterial blood under shear conditions typical to patent (424 sec-1) and stenosed (3397 sec-1) arteries, at baseline and after administration of the specific inhibitor of NO synthesis N omega-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 pressure, with a moderate reduction in heart rate. 51Cr platelet deposition on the exposed arterial media, which averaged 15.9 +/- 2.9 x 10(6)/cm2 at a shear rate of 424 sec-1, was increased by L-NAME, to 20.4 +/- 2.8 x 10(6)/cm2 (p < 0.05). At 3397 sec-1 of shear rate, platelet deposition was higher (71.4 +/- 11.9 x 10(6)/cm2) (p < 0.001), and was enhanced by 34%, to 95.8 +/- 12.5 x 10(6)/cm2 (p < 0.05), after L-NAME treatment. 111In neutrophil adhesion to the vascular endothelium was also increased by L-NAME by 83%, from 10.6 +/- 2.5 to 19.4 +/- 5.7 x 10(3)/cm2 (p < 0.05) at 424 sec-1, and by 110%, from 14.1 +/- 4.3 to 29.7 +/- 10.0 x 10(3)/cm2 (p < 0.05) at 3397 sec-1 of shear rate. These results suggest that endogenous NO may be an important modulator of thrombotic and inflammatory processes in patent as well as in stenosed arteries.
Provost
P
P
Laboratory of Experimental Pathology, Montreal Heart Institute, Quebec, Canada.
Merhi
Y
Y
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018056:Hemorheology; D006801:Humans; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D010974:Platelet Aggregation; D013552:Swine; D013927:Thrombosis / Q000378:metabolism*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester