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

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 hig...

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Autores principales: Greig, Fiona H., Ewart, Marie-Ann, McNaughton, Eilidh, Cooney, Josephine, Spickett, Corinne M., Kennedy, Simon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673085/
https://www.ncbi.nlm.nih.gov/pubmed/26196300
http://dx.doi.org/10.1016/j.vph.2015.07.010
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author Greig, Fiona H.
Ewart, Marie-Ann
McNaughton, Eilidh
Cooney, Josephine
Spickett, Corinne M.
Kennedy, Simon
author_facet Greig, Fiona H.
Ewart, Marie-Ann
McNaughton, Eilidh
Cooney, Josephine
Spickett, Corinne M.
Kennedy, Simon
author_sort Greig, Fiona H.
collection PubMed
description 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.
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spelling pubmed-46730852015-12-29 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 Vascul Pharmacol Article 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. Elsevier Science 2015-11 /pmc/articles/PMC4673085/ /pubmed/26196300 http://dx.doi.org/10.1016/j.vph.2015.07.010 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
title The hypotensive effect of acute and chronic AMP-activated protein kinase activation in normal and hyperlipidemic mice
title_full The hypotensive effect of acute and chronic AMP-activated protein kinase activation in normal and hyperlipidemic mice
title_fullStr The hypotensive effect of acute and chronic AMP-activated protein kinase activation in normal and hyperlipidemic mice
title_full_unstemmed The hypotensive effect of acute and chronic AMP-activated protein kinase activation in normal and hyperlipidemic mice
title_short The hypotensive effect of acute and chronic AMP-activated protein kinase activation in normal and hyperlipidemic mice
title_sort hypotensive effect of acute and chronic amp-activated protein kinase activation in normal and hyperlipidemic mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673085/
https://www.ncbi.nlm.nih.gov/pubmed/26196300
http://dx.doi.org/10.1016/j.vph.2015.07.010
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