Expression of inducible nitric oxide synthase inhibits platelet adhesion and restores blood flow in the injured artery

被引:106
作者
Yan, ZQ
Yokota, T
Zhang, WG
Hansson, GK
机构
[1] KAROLINSKA INST,DEPT MED,STOCKHOLM,SWEDEN
[2] KAROLINSKA INST,KING GUSTAF V RES INST,STOCKHOLM,SWEDEN
[3] KAROLINSKA INST,DEPT PHYSIOL & PHARMACOL,STOCKHOLM,SWEDEN
关键词
angioplasty; nitric oxide; platelet; blood flow; vascular smooth muscle;
D O I
10.1161/01.RES.79.1.38
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
NO generated by endothelial cells is vasoprotective by antagonizing platelet adhesion and smooth muscle contraction. Since vascular smooth muscle tells (VSMCs) produce NO in response to cytokine stimulation and after arterial injury, we speculated that NO produced by VSMCs could compensate for the loss of endothelium. Using balloon catheter denudation of the rat carotid artery as a model for arterial injury and restenosis. we have evaluated the timecourse of expression of inducible NO synthase (iNOS) by in situ hybridization and immunohistochemistry and studied the effect of iNOS on platelet adhesion and blood flow of the injured vessel. iNOS mRNA and protein were expressed in the innermost layer of the media from day 1 and were subsequently detected in the neointima, whereas no expression was detectable in the uninjured artery. Systemic administration of N-omega-nitro-L-arginine methyl ester (L-NAME) resulted in a twofold to threefold increase in the adhesion of In-111-labeled platelets to the injured vessel wall. Platelet adhesion was also enhanced threefold by local delivery of L-NAME from a gel surrounding the injured vessel, whereas the stereoisomer, D-NAME, had no effect. Finally, inhibition of NO synthase led to a 24% reduction of the blood flow in the injured carotid artery. These results demonstrate that arterial injury triggers the expression of iNOS in the lesion and that NO produced by iNOS inhibits platelet adhesion and restores blood flow. This could explain the disappearance of platelet thrombi from deendothelialized arterial surfaces within a few days after injury and indicates the importance of NO generated by iNOS for the maintenance of vascular tone. Thus, expression of iNOS in lesions may represent a protective mechanism that compensates for the loss of endothelium.
引用
收藏
页码:38 / 44
页数:7
相关论文
共 43 条
[1]   INDUCTION OF NITRIC-OXIDE SYNTHASE BY CYTOKINES IN VASCULAR SMOOTH-MUSCLE CELLS [J].
BUSSE, R ;
MULSCH, A .
FEBS LETTERS, 1990, 275 (1-2) :87-90
[2]   VASCULAR SMOOTH-MUSCLE CELL HEME OXYGENASES GENERATE GUANYLYL CYCLASE STIMULATORY CARBON-MONOXIDE [J].
CHRISTODOULIDES, N ;
DURANTE, W ;
KROLL, MH ;
SCHAFER, AI .
CIRCULATION, 1995, 91 (09) :2306-2309
[3]  
CLOWES AW, 1986, LAB INVEST, V54, P295
[4]   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
[5]   INHIBITION OF NEOINTIMAL SMOOTH-MUSCLE ACCUMULATION AFTER ANGIOPLASTY BY AN ANTIBODY TO PDGF [J].
FERNS, GAA ;
RAINES, EW ;
SPRUGEL, KH ;
MOTANI, AS ;
REIDY, MA ;
ROSS, R .
SCIENCE, 1991, 253 (5024) :1129-1132
[6]   ROLE OF PLATELETS IN SMOOTH-MUSCLE CELL-PROLIFERATION AND MIGRATION AFTER VASCULAR INJURY IN RAT CAROTID-ARTERY [J].
FINGERLE, J ;
JOHNSON, R ;
CLOWES, AW ;
MAJESKY, MW ;
REIDY, MA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (21) :8412-8416
[7]   REGULATION OF CALCIUM MOBILIZATION AND ENTRY IN HUMAN PLATELETS BY ENDOTHELIUM-DERIVED FACTORS [J].
GEIGER, J ;
NOLTE, C ;
WALTER, U .
AMERICAN JOURNAL OF PHYSIOLOGY, 1994, 267 (01) :C236-C244
[8]   INTERFERON-GAMMA AND TUMOR-NECROSIS-FACTOR SYNERGIZE TO INDUCE NITRIC-OXIDE PRODUCTION AND INHIBIT MITOCHONDRIAL RESPIRATION IN VASCULAR SMOOTH-MUSCLE CELLS [J].
GENG, Y ;
HANSSON, GK ;
HOLME, E .
CIRCULATION RESEARCH, 1992, 71 (05) :1268-1276
[9]   CDNA CLONING AND EXPRESSION OF INDUCIBLE NITRIC-OXIDE SYNTHASE FROM RAT VASCULAR SMOOTH-MUSCLE CELLS [J].
GENG, YJ ;
ALMQVIST, M ;
HANSSON, GK .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 1994, 1218 (03) :421-424
[10]   ENDOTHELIUM-DERIVED RELAXING FACTOR MODULATES PLATELET-AGGREGATION IN AN INVIVO MODEL OF RECURRENT PLATELET ACTIVATION [J].
GOLINO, P ;
CAPPELLIBIGAZZI, M ;
AMBROSIO, G ;
RAGNI, M ;
RUSSOLILLO, E ;
CONDORELLI, M ;
CHIARIELLO, M .
CIRCULATION RESEARCH, 1992, 71 (06) :1447-1456