Exercise training and losartan improve endothelial function in heart failure rats by different mechanisms

Kemi, O.J. , Haram, P.M., Høydal, M.A., Wisløff, U. and Ellingsen, Ø. (2013) Exercise training and losartan improve endothelial function in heart failure rats by different mechanisms. Scandinavian Cardiovascular Journal, 47(3), pp. 160-167. (doi: 10.3109/14017431.2012.754935)

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Abstract

Objectives. To investigate the mechanisms of losartan- and exercise training-induced improvements on endothelial dysfunction in heart failure. Design. Sprague-Dawley rats subjected to left coronary artery ligation inducing myocardial infarction and heart failure were randomized to losartan treatment, high-intensity exercise training, or both. Results. Losartan, but not exercise training, reduced the heart failure-associated elevation in left ventricular end-diastolic pressure (26 ± 2 mmHg vs. 19 ± 1 mmHg after losartan). In contrast, both exercise training and losartan improved exercise capacity, by 40% and 20%, respectively; no additional effects were observed when exercise training and losartan were combined. Aortic segments were mounted on a force transducer to determine vasorelaxation. Heart failure impaired endothelium-dependent vasorelaxation, observed as a 1.9-fold reduced response to acetylcholine (EC50). Exercise and losartan improved acetylcholine-mediated vasorelaxation to the same extent, but by different mechanisms. Exercise training upregulated the nitric oxide pathway, whereas losartan upregulated a non-nitric oxide or -prostacyclin pathway; possibly involving the endothelium-dependent hyperpolarizing factor. Conclusions. Both losartan and exercise training reversed endothelial dysfunction in heart failure; exercise training via nitric oxide-dependent vasorelaxation, and losartan via an unknown mechanism that may involve endothelium-dependent hyperpolarizing factor. Thus, the combined treatment activated an additional nitric oxide- independent mechanism that contributed to reduce endothelial dysfunction.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kemi, Dr Ole
Authors: Kemi, O.J., Haram, P.M., Høydal, M.A., Wisløff, U., and Ellingsen, Ø.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Scandinavian Cardiovascular Journal
Publisher:Informa Healthcare
ISSN:1401-7431
ISSN (Online):1651-2006
Published Online:03 January 2013
Copyright Holders:Copyright © 2012 2012 Informa Healthcare
First Published:First published in Scandinavian Cardiovascular Journal 47(3):160-167
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
529531Cardiac CaMK in heart failure and exercise trainingOle KemiBritish Heart Foundation (BHF)PG/09/107/28154RI CARDIOVASCULAR & MEDICAL SCIENCES