Open AccessEfficacy 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
Author(s) -
Rudolf A. de Boer,
Peter Paul van Geel,
Yigal M. Pinto,
Albert Suurmeijer,
Harry J.G.M. Crijns,
Wiek H. van Gilst,
Dirk J. van Veldhuisen
Publication year - 2002
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-200204000-00017
Subject(s) - losartan , angiotensin ii , blockade , medicine , myocardial infarction , renin–angiotensin system , endocrinology , ischemia , downregulation and upregulation , angiotensin ii receptor type 1 , receptor , cardiology , biology , blood pressure , biochemistry , gene
Angiotensin II induces ischemia/reperfusion (I/R)-induced arrhythmias and blockade of the angiotensin II type 1 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.