The hypotensive effect of acute and chronic AMP-activated protein kinase activation in normal and hyperlipidemic mice

Greig, F. H., Ewart, M.-A., McNaughton, E., Cooney, J., Spickett, C. M. and Kennedy, S. (2015) The hypotensive effect of acute and chronic AMP-activated protein kinase activation in normal and hyperlipidemic mice. Vascular Pharmacology, 74, pp. 93-102. (doi: 10.1016/j.vph.2015.07.010) (PMID:26196300) (PMCID:PMC4673085)

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Abstract

AMP-activated protein kinase (AMPK) is present in the arterial wall and is activated in response to cellular stressors that raise AMP relative to ADP/ATP. Activation of AMPK in vivo lowers blood pressure but the influence of hyperlipidemia on this response has not been studied. ApoE−/− mice on high fat diet for 6 weeks and age-matched controls were treated with the AMPK activator, AICAR daily for two weeks. Under anesthesia, the carotid artery was cannulated for blood pressure measurements. Aortic tissue was removed for in vitro functional experiments and AMPK activity was measured in artery homogenates by Western blotting. ApoE−/− mice had significantly raised mean arterial pressure; chronic AICAR treatment normalized this but had no effect in normolipidemic mice, whereas acute administration of AICAR lowered mean arterial pressure in both groups. Chronic AICAR treatment increased phosphorylation of AMPK and its downstream target acetyl-CoA carboxylase in normolipidemic but not ApoE−/− mice. In aortic rings, AMPK activation induced vasodilation and an anticontractile effect, which was attenuated in ApoE−/− mice. This study demonstrates that hyperlipidemia dysregulates the AMPK pathway in the arterial wall but this effect can be reversed by AMPK activation, possibly through improving vessel compliance.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cooney, Mrs Josephine and Kennedy, Professor Simon and Ewart, Dr Marie-Ann
Authors: Greig, F. H., Ewart, M.-A., McNaughton, E., Cooney, J., Spickett, C. M., and Kennedy, S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Vascular Pharmacology
Publisher:Elsevier
ISSN:1537-1891
ISSN (Online):1879-3649
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Vascular Pharmacology 74:93-102
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
495801Involvement of Chlorinated lipids in neointima formationSimon KennedyBritish Heart Foundation (BHF)FS/08/071/26212RI CARDIOVASCULAR & MEDICAL SCIENCES