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Effects of the Angiotensin II Subtype 1 Receptor Antagonist Losartan on Functional Recovery of Isolated Rat Hearts Undergoing Global Myocardial Ischemia‐Reperfusion
Author(s) -
Flynn Jeremy D.,
Akers Wendell S.
Publication year - 2003
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.23.14.1401.31947
Subject(s) - losartan , medicine , cardioprotection , ischemia , cardiology , ischemic preconditioning , reperfusion injury , angiotensin ii , myocardial infarction , anesthesia , blood pressure
Study Objective. To investigate the effects of the angiotensin II subtype 1 receptor (AT1R) antagonist losartan on functional recovery of isolated rat hearts undergoing global myocardial ischemia‐reperfusion compared with myocardial protective effects of ischemic preconditioning. Design. Ex vivo experiment using isolated perfused rat heart. Setting. Academic laboratory. Intervention. Hearts from Sprague‐Dawley rats were perfused with oxygenated Krebs‐Henseleit buffer and randomized to one of four groups: time control, vehicle, ischemic preconditioning, or losartan. Measurements and Main Results. After randomization, hearts underwent 30 minutes of global ischemia followed by 30 minutes of reperfusion. Changes in end‐diastolic pressure (EDP), left ventricular developed pressure (LVDP), and infarct size were examined between treatment groups by two‐way analysis of variance with repeated measures. Cardiac angiotensin II receptor (ATR) density and infarct size were measured in control hearts and in a subgroup of hearts exposed to ischemia‐reperfusion injury. Total ATR density and percentage of myocardial AT1R were increased in hearts exposed to ischemia‐reperfusion. Myocardial ischemia‐reperfusion injury resulted in a 56% reduction in LVDP from baseline in hearts randomized to vehicle. However, it declined by only 22% and 28% in hearts randomized to ischemic preconditioning and losartan, respectively. Compared with vehicle, both ischemic preconditioning and losartan decreased EDP (ischemic preconditioning 39 ± 3 mm Hg, losartan 54 ± 5 mm Hg, vs vehicle 78 ± 8 mm Hg), and reduced infarct size (ischemic preconditioning 9%, losartan 12%, vs vehicle 36%). Conclusion. Treatment of isolated rat hearts with losartan before ischemia‐reperfusion injury resulted in significant cardioprotection similar to that observed with ischemic preconditioning.