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- Publisher Website: 10.1111/bph.14716
- Scopus: eid_2-s2.0-85068501812
- PMID: 31116877
- WOS: WOS:000474124000001
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Article: Acute activation of endothelial AMPK surprisingly inhibits endothelium-dependent hyperpolarization-like relaxations in rat mesenteric arteries
Title | Acute activation of endothelial AMPK surprisingly inhibits endothelium-dependent hyperpolarization-like relaxations in rat mesenteric arteries |
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Authors | |
Keywords | Endothelium Vasodilation Resistance arteries |
Issue Date | 2019 |
Publisher | John Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1 |
Citation | British Journal of Pharmacology, 2019, v. 176 n. 16, p. 2905-2921 How to Cite? |
Abstract | Background and Purpose:
Endothelium‐dependent hyperpolarizations (EDHs) contribute to the regulation of peripheral resistance. They are initiated through opening of endothelial calcium‐activated potassium channels (KCa); the potassium ions released then diffuse to the underlying smooth muscle cells, causing hyperpolarization and thus relaxation. The present study aimed to examine whether or not AMPK modulates EDH‐like relaxations in rat mesenteric arteries.
Experimental Approach:
Arterial rings were isolated for isometric tension recording. AMPK activity and protein level were measured by ELISA and western blotting respectively.
Key Results:
The AMPK activator, AICAR, reduced ACh‐induced EDH‐like relaxations and increased AMPK activity in preparations with endothelium; these responses were prevented by compound C, an AMPK inhibitor. AICAR inhibited relaxations induced by SKA‐31 (opener of endothelial KCa) but did not affect potassium‐induced, hyperpolarization‐attributable relaxations or increase AMPK activity in preparations without endothelium. A769662, another AMPK activator, not only caused a similar inhibition of relaxations to ACh and SKA‐31 in preparations with endothelium but also inhibited hyperpolarization‐attributable relaxations and augmented AMPK activity in rings without endothelium. Protein levels of total AMPKα, AMPKα1, or AMPKβ1/2 were comparable between preparations with and without endothelium.
Conclusions and Implications:
Activation of endothelial AMPK, by either AICAR or A769662, acutely inhibits EDH‐like relaxations of rat mesenteric arteries. Furthermore, A769662 inhibits signalling downstream of smooth muscle hyperpolarization. In view of the major blunting effect of AMPK activation on EDH‐like relaxations, caution should be applied when administering therapeutic agents that activate AMPK in patients with endothelial dysfunction characterized by reduced production and/or bioavailability of NO. |
Persistent Identifier | http://hdl.handle.net/10722/273996 |
ISSN | 2023 Impact Factor: 6.8 2023 SCImago Journal Rankings: 2.119 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | CHEN, H | - |
dc.contributor.author | Vanhoutte, PM | - |
dc.contributor.author | Leung, SWS | - |
dc.date.accessioned | 2019-08-18T14:52:58Z | - |
dc.date.available | 2019-08-18T14:52:58Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | British Journal of Pharmacology, 2019, v. 176 n. 16, p. 2905-2921 | - |
dc.identifier.issn | 0007-1188 | - |
dc.identifier.uri | http://hdl.handle.net/10722/273996 | - |
dc.description.abstract | Background and Purpose: Endothelium‐dependent hyperpolarizations (EDHs) contribute to the regulation of peripheral resistance. They are initiated through opening of endothelial calcium‐activated potassium channels (KCa); the potassium ions released then diffuse to the underlying smooth muscle cells, causing hyperpolarization and thus relaxation. The present study aimed to examine whether or not AMPK modulates EDH‐like relaxations in rat mesenteric arteries. Experimental Approach: Arterial rings were isolated for isometric tension recording. AMPK activity and protein level were measured by ELISA and western blotting respectively. Key Results: The AMPK activator, AICAR, reduced ACh‐induced EDH‐like relaxations and increased AMPK activity in preparations with endothelium; these responses were prevented by compound C, an AMPK inhibitor. AICAR inhibited relaxations induced by SKA‐31 (opener of endothelial KCa) but did not affect potassium‐induced, hyperpolarization‐attributable relaxations or increase AMPK activity in preparations without endothelium. A769662, another AMPK activator, not only caused a similar inhibition of relaxations to ACh and SKA‐31 in preparations with endothelium but also inhibited hyperpolarization‐attributable relaxations and augmented AMPK activity in rings without endothelium. Protein levels of total AMPKα, AMPKα1, or AMPKβ1/2 were comparable between preparations with and without endothelium. Conclusions and Implications: Activation of endothelial AMPK, by either AICAR or A769662, acutely inhibits EDH‐like relaxations of rat mesenteric arteries. Furthermore, A769662 inhibits signalling downstream of smooth muscle hyperpolarization. In view of the major blunting effect of AMPK activation on EDH‐like relaxations, caution should be applied when administering therapeutic agents that activate AMPK in patients with endothelial dysfunction characterized by reduced production and/or bioavailability of NO. | - |
dc.language | eng | - |
dc.publisher | John Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1 | - |
dc.relation.ispartof | British Journal of Pharmacology | - |
dc.rights | Preprint This is the pre-peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Postprint This is the peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. | - |
dc.subject | Endothelium | - |
dc.subject | Vasodilation | - |
dc.subject | Resistance arteries | - |
dc.title | Acute activation of endothelial AMPK surprisingly inhibits endothelium-dependent hyperpolarization-like relaxations in rat mesenteric arteries | - |
dc.type | Article | - |
dc.identifier.email | Vanhoutte, PM: vanhoutt@hku.hk | - |
dc.identifier.email | Leung, SWS: swsleung@hku.hk | - |
dc.identifier.authority | Vanhoutte, PM=rp00238 | - |
dc.identifier.authority | Leung, SWS=rp00235 | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1111/bph.14716 | - |
dc.identifier.pmid | 31116877 | - |
dc.identifier.scopus | eid_2-s2.0-85068501812 | - |
dc.identifier.hkuros | 302376 | - |
dc.identifier.volume | 176 | - |
dc.identifier.issue | 16 | - |
dc.identifier.spage | 2905 | - |
dc.identifier.epage | 2921 | - |
dc.identifier.isi | WOS:000474124000001 | - |
dc.publisher.place | United Kingdom | - |
dc.identifier.issnl | 0007-1188 | - |