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

Research output: Contribution to journalArticle

View graph of relations Save citation

Open

Authors

Research units

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.

Documents

Details

Original languageEnglish
Pages (from-to)93-102
Number of pages10
JournalVascular Pharmacology
Volume74
Early online date18 Jul 2015
DOIs
Publication statusPublished - Nov 2015

Bibliographic note

© 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) Funding: British Heart Foundation (PhD studentship, FS/08/071/26212)

    Keywords

  • mean arterial blood pressure, hypotension, AMPK, AICAR, hyperlipidemia

Download statistics

No data available

Employable Graduates; Exploitable Research

Copy the text from this field...