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Exercise Training and Losartan Improve Endothelial Function in Heart Failure Rats by Different Mechanisms.
MedLine Citation:
PMID:  23205578     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 (EC(50)). 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.
Authors:
Ole Johan Kemi; Per Magnus Haram; Morten Andre Høydal; Ulrik Wisløff; Oyvind Ellingsen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-3
Journal Detail:
Title:  Scandinavian cardiovascular journal : SCJ     Volume:  -     ISSN:  1651-2006     ISO Abbreviation:  Scand. Cardiovasc. J.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9708377     Medline TA:  Scand Cardiovasc J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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