The role of angiotensin receptor-1 blockade on electromechanical changes induced by left ventricular hypertrophy and its regression
Gray, RP, Turner, MA, Sheridan, DJ and Fry, CH (2007) The role of angiotensin receptor-1 blockade on electromechanical changes induced by left ventricular hypertrophy and its regression CARDIOVASC RES, 73 (3). pp. 539-548.
Objective: The aims of this study were to: i) investigate the role of angiotensin in mediating changes to myocardial electromechanical properties during the development and regression of left ventricular hypertrophy (LVH) generated by constriction of the thoracic aorta; ii) identify any role of angiotensin-1 receptor blockade on ameliorating changes to these electromechanical properties. Methods: LVH was induced in guinea-pigs by constricting the ascending aorta (AC groups). After 42±3 days, the constriction was either removed or left in place. Following the second operation animals were fed losartan (10 mg·kg−1·day−1) or saline for 42±3 days. Sham-operated animals served as controls. In other groups, LVH was generated by subcutaneous angiotensin II (200 ng·kg−1·min−1) infusion for 42±3 days with or without losartan administration (AT groups), and compared to animals undergoing aortic constriction for a similar period. Electromechanical changes were recorded in isolated left ventricular myocardial preparations. Results: Wet and dry heart-to-body weight ratios (HBR) increased significantly in the AC and AT models compared to control. Losartan prevented the increase of HBR in the AT group. Removal of the constriction allowed LVH to regress to control. The force–frequency relationship was reduced in both models and recovered fully on regression. However, the two models generated different electrophysiological changes: in the AC group, longitudinal conduction velocity was reduced and transverse conduction increased, with a consequent reduction of the anisotropic conduction ratio. On regression recovery was only partial; action potential duration was prolonged and did not recover. In the AT group, electrophysiological changes were limited: only an increase of transverse conduction and a reduction of the anisotropic conduction ratio were observed. Losartan had no effect on HBR or electromechanical variables in the aortic constricted animals, nor did it affect the extent of recovery in animals with regression of LVH. Conclusions: The electromechanical changes to hypertrophied myocardium are different in these two models of LVH. Moreover, losartan was ineffective in modulating the consequences of hypertrophy induced by constriction of the thoracic aorta.
|Divisions :||Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Clinical and Experimental Medicine|
|Date :||1 February 2007|
|Identification Number :||10.1016/j.cardiores.2006.11.017|
|Uncontrolled Keywords :||hypertrophy, ventricular function, arrhythmia, angiotensin-receptor blockade, conduction, CONVERTING ENZYME-INHIBITION, PRESSURE-OVERLOAD HYPERTROPHY, ACTION-POTENTIAL CONDUCTION, GUINEA-PIG MYOCARDIUM, AORTIC-STENOSIS, CARDIAC-HYPERTROPHY, DIRECTIONAL DIFFERENCES, PROGNOSTIC IMPLICATIONS, VASCULAR HYPERTROPHY, VALVE-REPLACEMENT|
|Additional Information :||© 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. NOTICE: this is the author’s version of a work that was accepted for publication in Cardiovascular Research. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Cardiovascular Research, 73(3), February 2007, DOI: 10.1016/j.cardiores.2006.11.017|
|Depositing User :||Symplectic Elements|
|Date Deposited :||07 Mar 2012 16:12|
|Last Modified :||23 Sep 2013 19:05|
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