Publication

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

de Boer, RA., van Geel, PP., Pinto, YM., Suurmeijer, AJH., Crijns, HJGM., van Gilst, WH. & van Veldhuisen, DJ., Apr-2002, In : Journal of Cardiovascular Pharmacology. 39, 4, p. 610-619 10 p.

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)610-619
Number of pages10
JournalJournal of Cardiovascular Pharmacology
Volume39
Issue number4
Publication statusPublished - Apr-2002
Event23rd Congress of the European-Society-of-Cardiology - , Sweden
Duration: 1-Sep-20015-Sep-2001

Event

23rd Congress of the European-Society-of-Cardiology

01/09/200105/09/2001

Sweden

Event: Other

    Keywords

  • arrhythmias, infarction, ischemia, renin-angiotensin system, reperfusion, CONVERTING ENZYME-INHIBITORS, CORONARY-ARTERY OCCLUSION, AT(1) RECEPTOR, HEART-FAILURE, ISCHEMIA-REPERFUSION, RANDOMIZED TRIAL, QT DISPERSION, LOSARTAN, CAPTOPRIL, ACTIVATION

ID: 4005640