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Angiotensin II subtype 1 (AT 1 ) receptors contribute to ischemic contracture and regulate chemomechanical energy transduction in isolated transgenic rat (αMHC‐hAT 1 )594–17 hearts
Author(s) -
Han Hong,
Hoffmann Sigrid,
Hu Kai,
Ertl Georg
Publication year - 2002
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/s1388-9842(02)00005-3
Subject(s) - preload , medicine , ischemia , cardiology , angiotensin ii , receptor , endocrinology , anesthesia , hemodynamics
Background: The role of AT 1 receptors in myocardial ischemia/reperfusion injury is unclear. We, therefore, investigated the effects of the AT 1 receptor antagonist irbesartan (Irb) in isolated hearts of selective myocardial AT 1 overexpressing transgenic [transgenic(αMHC‐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 (MVO 2 ) were recorded continuously. Myocardial efficiency was derived from the slope of relations of MVO 2 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 AT 1 receptors in ischemic contracture, AT 1 ‐receptors also appear to be involved in the control of myocardial efficiency.