Document Detail

Effects of the angiotensin II subtype 1 receptor antagonist losartan on functional recovery of isolated rat hearts undergoing global myocardial ischemia-reperfusion.
MedLine Citation:
PMID:  14620386     Owner:  NLM     Status:  MEDLINE    
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.
Jeremy D Flynn; Wendell S Akers
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pharmacotherapy     Volume:  23     ISSN:  0277-0008     ISO Abbreviation:  Pharmacotherapy     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-11-17     Completed Date:  2004-03-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8111305     Medline TA:  Pharmacotherapy     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1401-10     Citation Subset:  IM    
Division of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington 40536-0082, USA.
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MeSH Terms
Angiotensin II Type 1 Receptor Blockers*
Heart / drug effects*,  physiology
Ischemic Preconditioning, Myocardial / methods
Losartan / metabolism,  pharmacology*,  therapeutic use*
Myocardial Reperfusion Injury / drug therapy*,  metabolism
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1 / metabolism
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Receptor, Angiotensin, Type 1; 114798-26-4/Losartan

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