Influence of the angiotensin II AT1 receptor antagonist irbesartan on ischemia/reperfusion injury in the dog heart

The aim of the present study was to investigate whether the non-peptide angiotensin II type 1 (AT1) receptor antagonist irbesartan (SR 47436, BMS 186295, 2-n-butyl-3 [2'-(1H-tetrazol-5-yl)-biphenyl-4-yl)methyl]-1,3-diaza-spiro [4,4]non-1-en-4-one) has myocardial protective effects during region...

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Bibliographic Details
Published in:Basic research in cardiology 2000-10, Vol.95 (5), p.404-412
Main Authors: Preckel, B, Schlack, W, Gonzàlez, M, Obal, D, Barthel, H, Thämer, V
Format: Article
Language:English
Subjects:
Angiotensin II - pharmacology
Angiotensin Receptor Antagonists
Animals
Biphenyl Compounds - pharmacology
Coronary Circulation - drug effects
Dogs
Heart - physiopathology
Hemodynamics - drug effects
Injections, Intravenous
Irbesartan
Myocardial Infarction - pathology
Myocardial Ischemia - pathology
Myocardial Ischemia - physiopathology
Myocardial Reperfusion Injury - pathology
Myocardial Reperfusion Injury - physiopathology
Myocardium - pathology
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Renin - blood
Tetrazoles - pharmacology
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Summary:The aim of the present study was to investigate whether the non-peptide angiotensin II type 1 (AT1) receptor antagonist irbesartan (SR 47436, BMS 186295, 2-n-butyl-3 [2'-(1H-tetrazol-5-yl)-biphenyl-4-yl)methyl]-1,3-diaza-spiro [4,4]non-1-en-4-one) has myocardial protective effects during regional myocardial ischemia/reperfusion in vivo. Eighteen anesthetized open-chest dogs were instrumented for measurement of left ventricular and aortic pressure (tip manometer and pressure transducer, respectively), and coronary flow (ultrasonic flowprobes). Regional myocardial function was assessed by Doppler displacement transducers as systolic wall thickening (sWT) in the antero-apical and the postero-basal wall. The animals underwent 1 h of left anterior descending coronary artery (LAD) occlusion and subsequent reperfusion for 3 hours. Irbesartan (10 mg kg(-1), n = 9) or the vehicle (KOH, control, n = 9) was injected intravenously 30 min before LAD occlusion. Regional myocardial blood flow (RMBF) was measured after irbesartan injection and at 30 min LAD occlusion using colored microspheres. Infarct size was determined by triphenyltetrazolium chloride staining after 3 h of reperfusion. There was no recovery of sWT in the LAD perfused area in both groups at the end of the experiments (systolic bulging, -15.1+/-6.1% of baseline (irbesartan) vs. -12.3+/-3.0% (control), mean+/-SEM). Irbesartan led to an increase in RMBF in normal myocardium (2.47+/-0.40 vs. 1.35+/-0.28 ml min(-1) g(-1), p
ISSN:0300-8428
DOI:10.1007/s003950070040