Selective adenosine A(3) receptor stimulation reduces ischemic myocardial injury in the rabbit heart

被引:101
作者
Tracey, WR
Magee, W
Masamune, H
Kennedy, SP
Knight, DR
Buchholz, RA
Hill, RJ
机构
[1] PFIZER INC,DEPT CARDIOVASC & METAB DIS,GROTON,CT 06340
[2] PFIZER INC,DEPT MED CHEM,GROTON,CT 06340
[3] PFIZER INC,DEPT MOL SCI,GROTON,CT 06340
关键词
adenosine receptor; rabbit; heart; preconditioning; myocardial infarction; myocardial ischemia; reperfusion;
D O I
10.1016/S0008-6363(96)00240-4
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: The aim of this study was to determine whether selective activation of the adenosine A(3) receptor reduces infarct size in a Langendorff model of myocardial ischemia-reperfusion injury. Methods: Buffer-perfused rabbit hearts were exposed to 30 min regional ischemia and 120 min of reperfusion. Infarct size was measured by tetrazolium staining and normalized for area-at-risk (IA/AAR), Results: Preconditioning by 5 min global ischemia and 10 min reperfusion reduced infarct size (ZA/AAR) to 19 +/- 4% (controls: 67 +/- 5%). Replacing global ischemia with 5 min perfusion of the rabbit A(3)-selective agonist, IB-MECA (A(3) K-i: 2 nM; A(1), K-i: 30 nM) elicited a concentration-dependent reduction in infarct size; 50 nM IB-MECA reduced IA/AAR to 24 +/- 4%. The A(1)-selective agonist, R-PIA (25 nM) reduced IA/AAR to a similar extent (21 +/- 6%). However, while the cardioprotective effect of R-PIA was significantly inhibited (54 +/- 7% IA/AAR) by the rabbit A(1)-selective antagonist, BWA1433 (50 nM), the IB-MECA-dependent cardioprotection was unaffected (28 +/- 6% IA/AAR). A non-selective (A(1) vs. A(3)) concentration of BWA1433 (5 mu M) significantly attenuated the IB-MECA-dependent cardioprotection (61 +/- 7% IA/AAR). Conclusions: These data clearly demonstrate that selective A(3) receptor activation provides cardioprotection from ischemia-reperfusion injury in the rabbit heart. Furthermore, the degree of A(3)-dependent cardioprotection is similar to that provided by A(1) receptor stimulation or ischemic preconditioning.
引用
收藏
页码:410 / 415
页数:6
相关论文
共 10 条
[1]   ADENOSINE RECEPTOR SPECIFICITY IN PRECONDITIONING OF ISOLATED RABBIT CARDIOMYOCYTES - EVIDENCE OF A(3) RECEPTOR INVOLVEMENT [J].
ARMSTRONG, S ;
GANOTE, CE .
CARDIOVASCULAR RESEARCH, 1994, 28 (07) :1049-1056
[2]  
ELY SW, 1985, J THORAC CARDIOV SUR, V90, P549
[3]   AN ADENOSINE-A1-RECEPTOR AGONIST, R(-)-N-(2-PHENYLISOPROPYL)-ADENOSINE (PIA), BUT NOT ADENOSINE ITSELF, ACTS AS A THERAPEUTIC PRECONDITIONING-MIMETIC AGENT IN RABBITS [J].
HALE, SL ;
BELLOWS, SD ;
HAMMERMAN, H ;
KLONER, RA .
CARDIOVASCULAR RESEARCH, 1993, 27 (12) :2140-2145
[4]  
Hill RJ, 1997, J PHARMACOL EXP THER, V280, P122
[5]   ADENOSINE-A1 RECEPTOR MEDIATED PROTECTION OF THE GLOBALLY ISCHEMIC ISOLATED RAT-HEART [J].
LASLEY, RD ;
RHEE, JW ;
VANWYLEN, DGL ;
MENTZER, RM .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1990, 22 (01) :39-47
[6]   EVIDENCE THAT THE ADENOSINE A(3) RECEPTOR MAY MEDIATE THE PROTECTION AFFORDED BY PRECONDITIONING IN THE ISOLATED RABBIT HEART [J].
LIU, GS ;
RICHARDS, SC ;
OLSSON, RA ;
MULLANE, KH ;
WALSH, RS ;
DOWNEY, JM .
CARDIOVASCULAR RESEARCH, 1994, 28 (07) :1057-1061
[7]   PROTECTION AGAINST INFARCTION AFFORDED BY PRECONDITIONING IS MEDIATED BY A1 ADENOSINE RECEPTORS IN RABBIT HEART [J].
LIU, GS ;
THORNTON, J ;
VANWINKLE, DM ;
STANLEY, AWH ;
OLSSON, RA ;
DOWNEY, JM .
CIRCULATION, 1991, 84 (01) :350-356
[8]   PRECONDITIONING WITH ISCHEMIA - A DELAY OF LETHAL CELL INJURY IN ISCHEMIC MYOCARDIUM [J].
MURRY, CE ;
JENNINGS, RB ;
REIMER, KA .
CIRCULATION, 1986, 74 (05) :1124-1136
[9]   INTRAVENOUS PRETREATMENT WITH A1-SELECTIVE ADENOSINE-ANALOGS PROTECTS THE HEART AGAINST INFARCTION [J].
THORNTON, JD ;
LIU, GS ;
OLSSON, RA ;
DOWNEY, JM .
CIRCULATION, 1992, 85 (02) :659-665
[10]   PRETREATMENT WITH THE ADENOSINE-A1 SELECTIVE AGONIST, 2-CHLORO-N6-CYCLOPENTYLADENOSINE (CCPA), CAUSES A SUSTAINED LIMITATION OF INFARCT SIZE IN RABBITS [J].
TSUCHIDA, A ;
LIU, GS ;
WILBORN, WH ;
DOWNEY, JM .
CARDIOVASCULAR RESEARCH, 1993, 27 (04) :652-656