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

Fiona H. Greig, Marie-Ann Ewart, Eilidh McNaughton, Josephine Cooney, Corinne M. Spickett, Simon Kennedy

Research output: Contribution to journalArticle

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.

LanguageEnglish
Pages93-102
Number of pages10
JournalVascular Pharmacology
Volume74
Early online date18 Jul 2015
DOIs
Publication statusPublished - Nov 2015

Fingerprint

AMP-Activated Protein Kinases
Apolipoproteins E
Hyperlipidemias
Arterial Pressure
Blood Pressure
Acetyl-CoA Carboxylase
High Fat Diet
Adenosine Monophosphate
Carotid Arteries
Vasodilation
Adenosine Diphosphate
Compliance
Anesthesia
Arteries
Adenosine Triphosphate
Western Blotting
Phosphorylation
AICA ribonucleotide

Bibliographical 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

Cite this

Greig, Fiona H. ; Ewart, Marie-Ann ; McNaughton, Eilidh ; Cooney, Josephine ; Spickett, Corinne M. ; Kennedy, Simon. / The hypotensive effect of acute and chronic AMP-activated protein kinase activation in normal and hyperlipidemic mice. In: Vascular Pharmacology. 2015 ; Vol. 74. pp. 93-102.
@article{93c68385ab8c46dfb8c8d95a2c1124b2,
title = "The hypotensive effect of acute and chronic AMP-activated protein kinase activation in normal and hyperlipidemic mice",
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.",
keywords = "mean arterial blood pressure, hypotension, AMPK, AICAR, hyperlipidemia",
author = "Greig, {Fiona H.} and Marie-Ann Ewart and Eilidh McNaughton and Josephine Cooney and Spickett, {Corinne M.} and Simon Kennedy",
note = "{\circledC} 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)",
year = "2015",
month = "11",
doi = "10.1016/j.vph.2015.07.010",
language = "English",
volume = "74",
pages = "93--102",
journal = "Vascular Pharmacology",
issn = "1537-1891",
publisher = "Elsevier",

}

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.; Kennedy, Simon.

In: Vascular Pharmacology, Vol. 74, 11.2015, p. 93-102.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The hypotensive effect of acute and chronic AMP-activated protein kinase activation in normal and hyperlipidemic mice

AU - Greig, Fiona H.

AU - Ewart, Marie-Ann

AU - McNaughton, Eilidh

AU - Cooney, Josephine

AU - Spickett, Corinne M.

AU - Kennedy, Simon

N1 - © 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)

PY - 2015/11

Y1 - 2015/11

N2 - 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.

AB - 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.

KW - mean arterial blood pressure

KW - hypotension

KW - AMPK

KW - AICAR

KW - hyperlipidemia

UR - http://www.scopus.com/inward/record.url?scp=84947618998&partnerID=8YFLogxK

U2 - 10.1016/j.vph.2015.07.010

DO - 10.1016/j.vph.2015.07.010

M3 - Article

VL - 74

SP - 93

EP - 102

JO - Vascular Pharmacology

T2 - Vascular Pharmacology

JF - Vascular Pharmacology

SN - 1537-1891

ER -