Cardioprotective effects of angiotensin II type 1 receptor blockade with olmesartan on reperfusion injury in a rat myocardial ischemia-reperfusion model

Cardiovasc Ther. Spring 2010;28(1):30-7. doi: 10.1111/j.1755-5922.2009.00108.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Animals
  • Cardiotonic Agents / pharmacology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Hemodynamics / drug effects
  • Imidazoles / pharmacology*
  • Myocardial Contraction / drug effects
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / prevention & control*
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocardium / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Tetrazoles / pharmacology*
  • Vasodilator Agents / pharmacology*
  • Ventricular Function, Left / drug effects

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Cardiotonic Agents
  • Imidazoles
  • Tetrazoles
  • Vasodilator Agents
  • olmesartan