MODULATION OF NEUTROPHIL ACTIVITY BY NITRIC-OXIDE DURING ACUTE MYOCARDIAL-ISCHEMIA AND REPERFUSION

被引:19
作者
EGDELL, RM [1 ]
SIMINIAK, T [1 ]
SHERIDAN, DJ [1 ]
机构
[1] ST MARYS HOSP, SCH MED, ACAD CARDIOL UNIT, LONDON W2 1NY, ENGLAND
关键词
NITRIC OXIDE; POLYMORPHONUCLEAR NEUTROPHILS; MYOCARDIAL ISCHEMIA; REPERFUSION; ENDOTHELIAL DYSFUNCTION;
D O I
10.1007/BF00794950
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Nitric oxide (NO) exerts an inhibitory effect on polymorphonuclear neutrophil (PMN) function, via a cyclic GMP-mediated mechanism, while PMNs are known to play an important role in myocardial ischaemia-reperfusion injury (MI-R). Since the major source of NO, vascular endothelium, becomes functionally impaired during MI-R, it is attractive to hypothesize that it is this loss of endothelial nitric oxide production that allows PMN adherence and activation. The studies reviewed here add substance to this hypothesis. Authentic NO, administered during MI-R both reduces myocardial necrosis and PMN accumulation, while basal NO release, as estimated by coronary artery ring responses to L-NAME, an NO synthase inhibitor, declines during reperfusion with a time-course mirrored by PMN adherence in the same preparation. Reduction in infarct size and decreased PMN accumulation can also be demonstrated with L-arginine and NO donors. Since endothelial dysfunction leads to PMN adherence and PMNs have been shown to contribute to endothelial dysfunction, it seems probable that a positive feedback loop is generated during MI-R, leading to the amplification of PMN activity and subsequent myocardial damage.
引用
收藏
页码:499 / 509
页数:11
相关论文
共 114 条
[1]   MYELOPEROXIDASE ACTIVITY AS A QUANTITATIVE MARKER OF POLYMORPHONUCLEAR LEUKOCYTE ACCUMULATION INTO AN EXPERIMENTAL MYOCARDIAL INFARCT - EFFECT OF IBUPROFEN ON INFARCT SIZE AND POLYMORPHONUCLEAR LEUKOCYTE ACCUMULATION [J].
ALLAN, G ;
BHATTACHERJEE, P ;
BROOK, CD ;
READ, NG ;
PARKE, AJ .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1985, 7 (06) :1154-1160
[2]  
[Anonymous], MECH VASODILATATION
[3]  
ARMIGER LC, 1975, LAB INVEST, V33, P51
[4]  
BECKER LC, 1989, ANAL SIMULATION CARD, P189
[5]   APPARENT HYDROXYL RADICAL PRODUCTION BY PEROXYNITRITE - IMPLICATIONS FOR ENDOTHELIAL INJURY FROM NITRIC-OXIDE AND SUPEROXIDE [J].
BECKMAN, JS ;
BECKMAN, TW ;
CHEN, J ;
MARSHALL, PA ;
FREEMAN, BA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (04) :1620-1624
[6]  
BENNETT BM, 1988, FASEB J, V2, pA1066
[7]   THE STUNNED MYOCARDIUM - PROLONGED, POST-ISCHEMIC VENTRICULAR DYSFUNCTION [J].
BRAUNWALD, E ;
KLONER, RA .
CIRCULATION, 1982, 66 (06) :1146-1149
[8]   MYOCARDIAL REPERFUSION - A DOUBLE-EDGED SWORD [J].
BRAUNWALD, E ;
KLONER, RA .
JOURNAL OF CLINICAL INVESTIGATION, 1985, 76 (05) :1713-1719
[9]   NEUTROPHIL ACCUMULATION IN EXPERIMENTAL MYOCARDIAL INFARCTS - RELATION WITH EXTENT OF INJURY AND EFFECT OF REPERFUSION [J].
CHATELAIN, P ;
LATOUR, JG ;
TRAN, D ;
DELORGERIL, M ;
DUPRAS, G ;
BOURASSA, M .
CIRCULATION, 1987, 75 (05) :1083-1090
[10]  
CONDINONETA A, 1992, BR J CLIN PHARM, V35, P485