ENDOTHELIUM-DERIVED RELAXING FACTOR INHIBITS PLATELET-ADHESION TO CULTURED PORCINE ENDOCARDIAL ENDOTHELIUM

被引:28
作者
SINEY, L [1 ]
LEWIS, MJ [1 ]
机构
[1] UNIV WALES COLL MED,DEPT PHARMACOL & TOXICOL,HEATH PK,CARDIFF CF4 4XN,S GLAM,WALES
关键词
EDRF (ENDOTHELIUM-DERIVED RELAXING FACTOR); PORCINE ENDOCARDIAL ENDOTHELIUM; HUMAN PLATELETS (WASHED); NO SYNTHASE INHIBITORS;
D O I
10.1016/0014-2999(92)90559-M
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
By using a simple platelet binding assay, we investigated whether endothelium-derived relaxing factor (EDRF) released from endocardial endothelium influences the adhesion of unstimulated platelets to these cells. Under basal conditions 8.0 +/- 0.32% of total platelets added adhered. The nitric oxide (NO) synthase inhibitor, i.e. N(G)-nitro L-arginine methyl ester (L-NAME), and the EDRF inhibitor haemoglobin (Hb) increased this adhesion, but another NO synthase inhibitor, N(G)-monomethyl L-arginine (L-NMMA), did not. The EDRF releasing agent substance P (SP) decreased adhesion, L-NMMA reversed this inhibition, whereas L-NAME and Hb did so only partially. Superoxide dismutase (SOD) caused a marked decrease in adhesion which was fully reversed by L-NMMA, L-NAME and Hb. SOD and SP together showed a cumulative effect on platelet adhesion; this inhibition was significantly reversed by all the EDRF inhibitors, although the levels of adhesion did not return to those seen under basal conditions. These results indicate that EDRF release can inhibit the adhesion of unstimulated platelets to cultured porcine endocardium and that NO synthase inhibitors have differential effects on basal and stimulated EDRF release by these cells.
引用
收藏
页码:223 / 226
页数:4
相关论文
共 13 条
[1]   HAPTOGLOBIN-HEMOGLOBIN COMPLEX IN HUMAN-PLASMA INHIBITS ENDOTHELIUM DEPENDENT RELAXATION - EVIDENCE THAT ENDOTHELIUM DERIVED RELAXING FACTOR ACTS AS A LOCAL AUTOCOID [J].
EDWARDS, DH ;
GRIFFITH, TM ;
RYLEY, HC ;
HENDERSON, AH .
CARDIOVASCULAR RESEARCH, 1986, 20 (08) :549-556
[2]   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
[3]   EXOGENOUS NITRIC-OXIDE INHIBITS INVIVO PLATELET-ADHESION FOLLOWING BALLOON ANGIOPLASTY [J].
GROVES, PH ;
PENNY, WJ ;
CHEADLE, HA ;
LEWIS, MJ .
CARDIOVASCULAR RESEARCH, 1992, 26 (06) :615-619
[4]   SUPEROXIDE ANION IS INVOLVED IN THE BREAKDOWN OF ENDOTHELIUM-DERIVED VASCULAR RELAXING FACTOR [J].
GRYGLEWSKI, RJ ;
PALMER, RMJ ;
MONCADA, S .
NATURE, 1986, 320 (6061) :454-456
[5]  
HUTCHINSON PJA, 1987, EUR J PHARMACOL, V141, P145
[6]   THE MECHANISMS BY WHICH HEMOGLOBIN INHIBITS THE RELAXATION OF RABBIT AORTA INDUCED BY NITROVASODILATORS, NITRIC-OXIDE, OR BOVINE RETRACTOR PENIS INHIBITORY FACTOR [J].
MARTIN, W ;
SMITH, JA ;
WHITE, DG .
BRITISH JOURNAL OF PHARMACOLOGY, 1986, 89 (03) :563-571
[7]   NITRIC-OXIDE RELEASE ACCOUNTS FOR THE BIOLOGICAL-ACTIVITY OF ENDOTHELIUM-DERIVED RELAXING FACTOR [J].
PALMER, RMJ ;
FERRIGE, AG ;
MONCADA, S .
NATURE, 1987, 327 (6122) :524-526
[8]  
POHL U, 1986, J APPL CARDIOL, V1, P215
[9]   ENDOGENOUS NITRIC-OXIDE INHIBITS HUMAN-PLATELET ADHESION TO VASCULAR ENDOTHELIUM [J].
RADOMSKI, MW ;
PALMER, RMJ ;
MONCADA, S .
LANCET, 1987, 2 (8567) :1057-1058
[10]   CHARACTERIZATION OF 3 INHIBITORS OF ENDOTHELIAL NITRIC-OXIDE SYNTHASE INVITRO AND INVIVO [J].
REES, DD ;
PALMER, RMJ ;
SCHULZ, R ;
HODSON, HF ;
MONCADA, S .
BRITISH JOURNAL OF PHARMACOLOGY, 1990, 101 (03) :746-752