Endogenous nitric oxide release modulates mural platelet thrombosis and neutrophil-endothelium interactions under low and high shear conditions

被引:22
作者
Provost, P
Merhi, Y
机构
[1] MONTREAL HEART INST, LAB EXPT PATHOL, MONTREAL, PQ H1T 1C8, CANADA
[2] UNIV MONTREAL, MONTREAL, PQ, CANADA
关键词
L-NAME; platelet; leukocyte; vessel wall; shear rate;
D O I
10.1016/S0049-3848(97)00017-0
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. 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 deposition was higher (71.4+/-11.9 x 10(6)/cm(2)) (p <0.001), and was enhanced by 34%, to 95.8+/-12.5 x 10(6)/cm(2) (p <0.05), after L-NAME treatment. In-111 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)/cm(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 results suggest that endogenous NO may be an important modulator of thrombotic and inflammatory processes in patent as well as in stenosed arteries. Copyright (C) 1997 Elsevier Science Ltd.
引用
收藏
页码:315 / 326
页数:12
相关论文
共 45 条
[1]  
BADIMON L, 1987, ANN NY ACAD SCI, V516, P527
[2]   INFLUENCE OF ARTERIAL DAMAGE AND WALL SHEAR RATE ON PLATELET DEPOSITION - EXVIVO STUDY IN A SWINE MODEL [J].
BADIMON, L ;
BADIMON, JJ ;
GALVEZ, A ;
CHESEBRO, JH ;
FUSTER, V .
ARTERIOSCLEROSIS, 1986, 6 (03) :312-320
[3]  
BAZZONI G, 1991, HAEMATOLOGICA, V76, P491
[4]   CHRONIC INHIBITION OF NITRIC-OXIDE PRODUCTION ACCELERATES NEOINTIMA FORMATION AND IMPAIRS ENDOTHELIAL FUNCTION IN HYPERCHOLESTEROLEMIC RABBITS [J].
CAYATTE, AJ ;
PALACINO, JJ ;
HORTEN, K ;
COHEN, RA .
ARTERIOSCLEROSIS AND THROMBOSIS, 1994, 14 (05) :753-759
[5]   NITRIC-OXIDE, AN ENDOTHELIAL-CELL RELAXATION FACTOR, INHIBITS NEUTROPHIL SUPEROXIDE ANION PRODUCTION VIA A DIRECT ACTION ON THE NADPH OXIDASE [J].
CLANCY, RM ;
LESZCZYNSKAPIZIAK, J ;
ABRAMSON, SB .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (03) :1116-1121
[6]   BLOCKADE OF PLATELET GPIIB/IIIA RECEPTORS AS AN ANTITHROMBOTIC STRATEGY [J].
COLLER, BS .
CIRCULATION, 1995, 92 (09) :2373-2380
[7]   NITRIC-OXIDE FUNCTIONS AS AN INHIBITOR OF PLATELET-ADHESION UNDER FLOW CONDITIONS [J].
DEGRAAF, JC ;
BANGA, JD ;
MONCADA, S ;
PALMER, RMJ ;
DEGROOT, PG ;
SIXMA, JJ .
CIRCULATION, 1992, 85 (06) :2284-2290
[8]   NITRIC-OXIDE REDUCES HYDROGEN-PEROXIDE PRODUCTION FROM HUMAN POLYMORPHONUCLEAR NEUTROPHILS [J].
FORSLUND, T ;
SUNDQVIST, T .
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 1995, 25 (01) :9-14
[9]   ATHEROSCLEROSIS IMPAIRS ENDOTHELIUM-DEPENDENT VASCULAR RELAXATION TO ACETYLCHOLINE AND THROMBIN IN PRIMATES [J].
FREIMAN, PC ;
MITCHELL, GG ;
HEISTAD, DD ;
ARMSTRONG, ML ;
HARRISON, DG .
CIRCULATION RESEARCH, 1986, 58 (06) :783-789
[10]   ENDOTHELIUM-DERIVED RELAXING FACTOR INHIBITS INVITRO PLATELET-AGGREGATION [J].
FURLONG, B ;
HENDERSON, AH ;
LEWIS, MJ ;
SMITH, JA .
BRITISH JOURNAL OF PHARMACOLOGY, 1987, 90 (04) :687-692