© 2002 European Society of Cardiology
Angiotensin II subtype 1 (AT1) receptors contribute to ischemic contracture and regulate chemomechanical energy transduction in isolated transgenic rat (
MHC-hAT1)594-17 hearts
a Department of Medicine, Medizinische Universitätsklinik, Universität Würzburg Josef-Schneider Strasse 2, Würzburg 97080, Germany
b Zentrum für Medizinische Forschung Universitätsklinikum Mannheim der Universität Heidelberg, Mannheim, Germany
* Corresponding author. Tel.: +49-931-201-5301; fax: +49-931-201-3453. E-mail address: g.ertl{at}medizin.uni-wuerzburg.de
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Abstract |
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Background: The role of AT1 receptors in myocardial ischemia/reperfusion injury is unclear. We, therefore, investigated the effects of the AT1 receptor antagonist irbesartan (Irb) in isolated hearts of selective myocardial AT1 overexpressing transgenic [transgenic(
MHC-hAT1)594-17] and Sprague–Dawley rats (SD) subjected to ischemia/reperfusion injury.
Methods and results: Hearts of 4-week-old male SD or transgenic rats were isolated and perfused with Krebs–Henseleit buffer with or without 10 µM Irb in Langendorff mode. After 15 min of stabilization, pressure–volume curves were obtained and the hearts subjected to 20 min ischemia followed by 30 min reperfusion. A second set of pressure–volume curves was obtained thereafter. Left ventricular developed pressure (LVDP), end-diastolic pressure (LVEDP), total coronary flow (CF) and oxygen consumption (MVO2) were recorded continuously. Myocardial efficiency was derived from the slope of relations of MVO2 to pressure/volume area. After 20 min ischemia, LVEDP was significantly higher in transgenic than in SD (35.7±1.8 vs. 29.2±1.0 mmHg, P<0.05) or Irb treated transgenic hearts (24.3±1.6 mmHg, P<0.05). Myocardial efficiency was increased by Irb before ischemia. Ischemia increased efficiency in SD but not in transgenic rats, Irb increased efficiency in transgenic hearts post-ischemia.
Conclusion: Transgenic hearts developed ischemic contracture more rapidly than SD hearts as indicated by higher LVEDP during ischemia. This response was antagonized by Irb, indicating a role of AT1 receptors in ischemic contracture, AT1-receptors also appear to be involved in the control of myocardial efficiency.
Key Words: Angiotensin • Receptor overexpression • Ischemia • Reperfusion
Received February 6, 2001; Revised June 27, 2001; Accepted December 14, 2001
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