Efficacy of angiotensin II type 1 receptor blockade on reperfusion-induced arrhythmias and mortality early after myocardial infarction is increased in transgenic rats with cardiac angiotensin II type 1 overexpression

被引:18
作者
de Boer, RA
van Geel, PP
Pinto, YM
Suurmeijer, AJH
Crijns, HJGM
van Gilst, WH
van Veldhuisen, DJ
机构
[1] Univ Groningen Hosp, Thoraxctr, Dept Cardiol, NL-9700 RB Groningen, Netherlands
[2] Univ Groningen Hosp, Dept Clin Pharmacol, NL-9700 RB Groningen, Netherlands
[3] Max Delbruck Ctr Mol Med, Berlin, Germany
[4] Univ Groningen Hosp, Dept Pathol, NL-9700 RB Groningen, Netherlands
关键词
arrhythmias; infarction; ischemia; renin-angiotensin system; reperfusion;
D O I
10.1097/00005344-200204000-00017
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Angiotensin II induces ischemia/reperfusion (I/R)-induced arrhythmias and blockade of the angiotensin II type I receptor (AT1R) may therefore be beneficial in preventing arrhythmias and decreasing mortality after myocardial infarction (MI). Because the AT1R is upregulated after myocardial ischemia, it was hypothesized that the level of AT1R expression would mediate the response to AT1R blockade. Transgenic (TGR) rats that overexpress the human AT1R and Sprague-Dawley rats were used as controls. Total duration of arrhythmia (seconds) after I/R injury was similar in TGR and SD rats (433 +/- 109 vs. 376 +/- 117, p = n.s.). AT1R blockade with losartan decreased total duration of arrhythmia in the TGR rats (433 +/- 110 s-164 +/- 48 s; p < 0.05), whereas it caused a nonsignificant increase in the SD rats (376 +/- 117 s-497 +/- 97). In vivo, survival in the first 24 hours after MI was impaired in TGR rats (39%; SD, 63%). Losartan improved survival significantly in TGR rats (from 39% to 80%, p < 0.05). A smaller, nonsignificant effect was observed in SD rats (63% to 81%). AT1R blockade is beneficial only when the AT1R was overexpressed, both in reducing the reperfusion-induced arrhythmias and mortality early after MI.
引用
收藏
页码:610 / 619
页数:10
相关论文
共 55 条
[1]   Effects of losartan and captopril on QT dispersion in elderly patients with heart failure [J].
Brooksby, P ;
Robinson, PJ ;
Segal, R ;
Klinger, G ;
Pitt, B ;
Cowley, AJC .
LANCET, 1999, 354 (9176) :395-396
[2]  
CHRIST DD, 1990, 3 N AM M INT SOC STU, P464
[3]   EFFECTS OF ANGIOTENSIN-II AND CAPTOPRIL ON INDUCIBLE SUSTAINED VENTRICULAR-TACHYCARDIA 2 WEEKS AFTER MYOCARDIAL-INFARCTION IN THE PIG [J].
DELANGEN, CDJ ;
DEGRAEFF, PA ;
VANGILST, WH ;
BEL, KJ ;
KINGMA, JH ;
WESSELING, H .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1989, 13 (02) :186-191
[4]   Renin-angiotensin system components in the interstitial fluid of the isolated perfused rat heart - Local production of angiotensin I [J].
deLannoy, LM ;
Danser, AHJ ;
vanKats, JP ;
Schoemaker, RG ;
Saxena, PR ;
Schalekamp, MADH .
HYPERTENSION, 1997, 29 (06) :1240-1251
[5]   CARDIAC REFRACTORINESS IN RATS IS REDUCED BY ANGIOTENSIN-II [J].
DEMELLO, WC ;
CRESPO, MJ .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1995, 25 (01) :51-56
[6]   Comparison of the effects of losartan and captopril on mortality in patients after acute myocardial infarction:: The OPTIMAAL trial design [J].
Dickstein, K ;
Kjekshus, J .
AMERICAN JOURNAL OF CARDIOLOGY, 1999, 83 (04) :477-481
[7]   Opposite effects of angiotensin AT(1) and AT(2) receptor antagonists on recovery of mechanical function after ischemia-reperfusion in isolated working rat hearts [J].
Ford, WR ;
Clanachan, AS ;
Jugdutt, BI .
CIRCULATION, 1996, 94 (12) :3087-3089
[8]  
Harada K, 1998, CIRCULATION, V97, P315
[9]  
HARTMAN JC, 1993, EUR J PHARMACOL, V234, P229
[10]   Renal function, neurohormonal activation, and survival in patients with chronic heart failure [J].
Hillege, HL ;
Girbes, ARJ ;
de Kam, PJ ;
Boomsma, F ;
de Zeeuw, D ;
Charlesworth, A ;
Hampton, JR ;
van Veldhuisen, DJ .
CIRCULATION, 2000, 102 (02) :203-+