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Angiotensin II subtype 1 (AT1) receptors contribute to ischemic contracture and regulate chemomechanical energy transduction in isolated transgenic rat (alphaMHC-hAT1)594-17 hearts.
Eur J Heart Fail. 2002 Mar; 4(2):131-7.EJ

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.

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 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.

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.

Authors+Show Affiliations

Department of Medicine, Medizinische Universitätsklinik, Universität Würzburg, Josef-Schneider Strasse 2, 97080, Würzburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11959040

Citation

Han, Hong, et al. "Angiotensin II Subtype 1 (AT1) Receptors Contribute to Ischemic Contracture and Regulate Chemomechanical Energy Transduction in Isolated Transgenic Rat (alphaMHC-hAT1)594-17 Hearts." European Journal of Heart Failure, vol. 4, no. 2, 2002, pp. 131-7.
Han H, Hoffmann S, Hu K, et al. Angiotensin II subtype 1 (AT1) receptors contribute to ischemic contracture and regulate chemomechanical energy transduction in isolated transgenic rat (alphaMHC-hAT1)594-17 hearts. Eur J Heart Fail. 2002;4(2):131-7.
Han, H., Hoffmann, S., Hu, K., & Ertl, G. (2002). Angiotensin II subtype 1 (AT1) receptors contribute to ischemic contracture and regulate chemomechanical energy transduction in isolated transgenic rat (alphaMHC-hAT1)594-17 hearts. European Journal of Heart Failure, 4(2), 131-7.
Han H, et al. Angiotensin II Subtype 1 (AT1) Receptors Contribute to Ischemic Contracture and Regulate Chemomechanical Energy Transduction in Isolated Transgenic Rat (alphaMHC-hAT1)594-17 Hearts. Eur J Heart Fail. 2002;4(2):131-7. PubMed PMID: 11959040.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin II subtype 1 (AT1) receptors contribute to ischemic contracture and regulate chemomechanical energy transduction in isolated transgenic rat (alphaMHC-hAT1)594-17 hearts. AU - Han,Hong, AU - Hoffmann,Sigrid, AU - Hu,Kai, AU - Ertl,Georg, PY - 2002/4/18/pubmed PY - 2002/5/25/medline PY - 2002/4/18/entrez SP - 131 EP - 7 JF - European journal of heart failure JO - Eur J Heart Fail VL - 4 IS - 2 N2 - 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. 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 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. 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. SN - 1388-9842 UR - https://www.unboundmedicine.com/medline/citation/11959040/Angiotensin_II_subtype_1__AT1__receptors_contribute_to_ischemic_contracture_and_regulate_chemomechanical_energy_transduction_in_isolated_transgenic_rat__alphaMHC_hAT1_594_17_hearts_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=1388-9842&amp;date=2002&amp;volume=4&amp;issue=2&amp;spage=131 DB - PRIME DP - Unbound Medicine ER -