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

Greig, Fiona H., Ewart, Marie-Ann, McNaughton, Eilidh, Cooney, Josephine, Spickett, Corinne M. and Kennedy, Simon (2015). The hypotensive effect of acute and chronic AMP-activated protein kinase activation in normal and hyperlipidemic mice. Vascular Pharmacology, 74 , pp. 93-102.

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.

Publication DOI: https://doi.org/10.1016/j.vph.2015.07.010
Divisions: Life & Health Sciences > Biosciences
Life & Health Sciences
Additional Information: © 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)
Uncontrolled Keywords: mean arterial blood pressure,hypotension,AMPK,AICAR,hyperlipidemia,Pharmacology,Molecular Medicine,Physiology
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2015-11
Authors: Greig, Fiona H.
Ewart, Marie-Ann
McNaughton, Eilidh
Cooney, Josephine
Spickett, Corinne M. ( 0000-0003-4054-9279)
Kennedy, Simon

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