Cardioprotective effects of angiotensin II type 1 receptor blockade with olmesartan on reperfusion injury in a rat myocardial ischemia-reperfusion model.
We determined the effects of olmesartan on infarct size and cardiac function in a rat ischemia/reperfusion model. Rats underwent 30 min of left coronary artery (CA) occlusion followed by 2 h of reperfusion. In protocol 1, the rats received (by i.v.) 1 mL of vehicle at 10 min after CA occlusion (Group 1, n = 15); olmesartan (0.3 mg/kg) at 10 min after CA occlusion (Group 2, n = 15); 1 mL of vehicle at 5 min before CA reperfusion (Group 3, n = 15); or olmesartan (0.3 mg/kg) 5 min before CA reperfusion (Group 4, n = 15). In protocol 2, the rats received (by i.v.) 1 mL of vehicle at 5 min before CA reperfusion (Group 5, n = 21); or olmesartan (3 mg/kg) at 5 min before CA reperfusion (Group 6, n = 21). Systemic hemodynamics, left ventricular (LV) function, LV ischemic risk zone, no-reflow zone, and infarct size were determined. In protocol 1, olmesartan (0.3 mg/kg) did not affect blood pressure (BP), heart rate, LV +/- dp/dt or LV fractional shortening during the experimental procedure, and did not alter no-reflow or infarct size. In protocol 2, olmesartan (3 mg/kg) significantly reduced infarct size to 21.7 +/- 4.1% from 34.3 +/- 4.1% of risk zone in the vehicle group (P= 0.035), but did not alter the no-reflow size. Prior to CA reperfusion, olmesartan (3 mg/kg) significantly reduced mean BP by 22% and LV +/-dp/dt, but did not affect heart rate. At 2 h after reperfusion, olmesartan significantly decreased heart rate by 21%, mean BP by 14%, and significantly increased LV fractional shortening from 54.1 +/- 1.4% to 61.3 +/- 1.6% (P= 0.0018). Olmesartan significantly reduced myocardial infarct size and improved LV contractility at a dose (3 mg/kg) with systemic vasodilating effects but not at a lower dose (0.3 mg/kg) without hemodynamic effects.
Dai
Wangde
W
The Heart Institute of Good Samaritan Hospital, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Hale
Sharon L
SL
Kay
Gregory L
GL
Jyrala
Aarne J
AJ
Kloner
Robert A
RA
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D002316:Cardiotonic Agents; D007093:Imidazoles; D013777:Tetrazoles; D014665:Vasodilator Agents; C437965:olmesartan