title: Angiotensin II subtype 1 (AT1) receptors contribute to ischemic contracture and regulate chemomechanical energy transduction in isolated transgenic rat (alphaMHC-hAT1)594-17 hearts.
abstract: 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(alphaMHC-hAT1)594-17] and Sprague-Dawley rats (SD) subjected to ischemia/reperfusion injury.
  
  
  RESULTS
  Hearts of 4-week-old male SD or transgenic rats were isolated and perfused with Krebs-Henseleit buffer with or without 10 microM 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Medizinische Universitätsklinik, Universität Würzburg, Josef-Schneider Strasse 2, 97080, Würzburg, Germany.
authors.forename: Hong
authors.initials: H
authors.lastname: Han
authors.forename: Sigrid
authors.initials: S
authors.lastname: Hoffmann
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002950:Citrate (si)-Synthase / Q000032:analysis / Q000187:drug effects; D003402:Creatine Kinase / Q000032:analysis / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000187:drug effects; D008297:Male; D008955:Models, Cardiovascular; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000008:administration & dosage*; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D014693:Ventricular Fibrillation / Q000150:complications / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D007770:L-Lactate Dehydrogenase; D002950:Citrate (si)-Synthase; D003402:Creatine Kinase