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

Journal of Cardiovascular Pharmacology
Rudolf A de BoerDirk J van Veldhuisen

Abstract

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.

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Citations

Feb 11, 2012·Molecular Endocrinology·Rekha YesudasThomas Thekkumkara
Jul 28, 2004·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Denan JinMizuo Miyazaki
Jul 18, 2012·The Journal of Steroid Biochemistry and Molecular Biology·Laura M G MeemsRudolf A de Boer
Mar 7, 2006·The American Journal of Cardiology·Shaila GargDavid Cesario
Jul 19, 2005·Experimental Neurology·Maria José Alves RochaMariana Morris
Dec 18, 2018·Canadian Journal of Physiology and Pharmacology·Adriana AdameovaNaranjan S Dhalla
Jan 20, 2004·The Journal of Pharmacology and Experimental Therapeutics·Denan JinMizuo Miyazaki
Jun 18, 2020·International Journal of Molecular Sciences·Adriana AdameovaNaranjan S Dhalla

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