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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Science
2015
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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. |
format | Online Article Text |
id | pubmed-4673085 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier Science |
record_format | MEDLINE/PubMed |
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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