Effects of the angiotensin II subtype 1 receptor antagonist losartan on functional recovery of isolated rat hearts undergoing global myocardial ischemia-reperfusion.
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.


METHODS
Ex vivo experiment using isolated perfused rat heart.


METHODS
Academic laboratory.


METHODS
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.


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%).


CONCLUSIONS
Treatment of isolated rat hearts with losartan before ischemia-reperfusion injury resulted in significant cardioprotection similar to that observed with ischemic preconditioning.
Flynn
Jeremy D
JD
Division of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington 40536-0082, USA.
Akers
Wendell S
WS
D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D019808:Losartan / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D019808:Losartan