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Cyclooxygenase metabolism mediates vasorelaxation to 2-arachidonoylglycerol (2-AG) in human mesenteric arteries
OBJECTIVE: The vasorelaxant effect of 2-arachidonoylglycerol (2-AG) has been well characterised in animals. 2-AG is present in human vascular cells and is up-regulated in cardiovascular pathophysiology. However, the acute vascular actions of 2-AG have not been explored in humans. APPROACH: Mesenteri...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Academic Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992009/ https://www.ncbi.nlm.nih.gov/pubmed/24548820 http://dx.doi.org/10.1016/j.phrs.2014.02.001 |
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author | Stanley, Christopher P. O'Sullivan, Saoirse E. |
author_facet | Stanley, Christopher P. O'Sullivan, Saoirse E. |
author_sort | Stanley, Christopher P. |
collection | PubMed |
description | OBJECTIVE: The vasorelaxant effect of 2-arachidonoylglycerol (2-AG) has been well characterised in animals. 2-AG is present in human vascular cells and is up-regulated in cardiovascular pathophysiology. However, the acute vascular actions of 2-AG have not been explored in humans. APPROACH: Mesenteric arteries were obtained from patients receiving colorectal surgery and mounted on a myograph. Arteries were contracted and 2-AG concentration–response curves were carried out. Mechanisms of action were characterised pharmacologically. Post hoc analysis was carried out to assess the effects of cardiovascular disease/risk factors on 2-AG responses. RESULTS: 2-AG caused vasorelaxation of human mesenteric arteries, independent of cannabinoid receptor or transient receptor potential vanilloid-1 activation, the endothelium, nitric oxide or metabolism via monoacyglycerol lipase or fatty acid amide hydrolase. 2-AG-induced vasorelaxation was reduced in the presence of indomethacin and flurbiprofen, suggesting a role for cyclooxygenase metabolism 2-AG. Responses to 2-AG were also reduced in the presence of Cay10441, L-161982 and potentiated in the presence of AH6809, suggesting that metabolism of 2-AG produces both vasorelaxant and vasoconstrictor prostanoids. Finally, 2-AG-induced vasorelaxation was dependent on potassium efflux and the presence of extracellular calcium. CONCLUSIONS: We have shown for the first time that 2-AG causes vasorelaxation of human mesenteric arteries. Vasorelaxation is dependent on COX metabolism, activation of prostanoid receptors (EP(4) & IP) and ion channel modulation. 2-AG responses are blunted in patients with cardiovascular risk factors. |
format | Online Article Text |
id | pubmed-3992009 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Academic Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-39920092014-04-23 Cyclooxygenase metabolism mediates vasorelaxation to 2-arachidonoylglycerol (2-AG) in human mesenteric arteries Stanley, Christopher P. O'Sullivan, Saoirse E. Pharmacol Res Article OBJECTIVE: The vasorelaxant effect of 2-arachidonoylglycerol (2-AG) has been well characterised in animals. 2-AG is present in human vascular cells and is up-regulated in cardiovascular pathophysiology. However, the acute vascular actions of 2-AG have not been explored in humans. APPROACH: Mesenteric arteries were obtained from patients receiving colorectal surgery and mounted on a myograph. Arteries were contracted and 2-AG concentration–response curves were carried out. Mechanisms of action were characterised pharmacologically. Post hoc analysis was carried out to assess the effects of cardiovascular disease/risk factors on 2-AG responses. RESULTS: 2-AG caused vasorelaxation of human mesenteric arteries, independent of cannabinoid receptor or transient receptor potential vanilloid-1 activation, the endothelium, nitric oxide or metabolism via monoacyglycerol lipase or fatty acid amide hydrolase. 2-AG-induced vasorelaxation was reduced in the presence of indomethacin and flurbiprofen, suggesting a role for cyclooxygenase metabolism 2-AG. Responses to 2-AG were also reduced in the presence of Cay10441, L-161982 and potentiated in the presence of AH6809, suggesting that metabolism of 2-AG produces both vasorelaxant and vasoconstrictor prostanoids. Finally, 2-AG-induced vasorelaxation was dependent on potassium efflux and the presence of extracellular calcium. CONCLUSIONS: We have shown for the first time that 2-AG causes vasorelaxation of human mesenteric arteries. Vasorelaxation is dependent on COX metabolism, activation of prostanoid receptors (EP(4) & IP) and ion channel modulation. 2-AG responses are blunted in patients with cardiovascular risk factors. Academic Press 2014-03 /pmc/articles/PMC3992009/ /pubmed/24548820 http://dx.doi.org/10.1016/j.phrs.2014.02.001 Text en © 2014 The Authors http://creativecommons.org/licenses/by/3.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Stanley, Christopher P. O'Sullivan, Saoirse E. Cyclooxygenase metabolism mediates vasorelaxation to 2-arachidonoylglycerol (2-AG) in human mesenteric arteries |
title | Cyclooxygenase metabolism mediates vasorelaxation to 2-arachidonoylglycerol (2-AG) in human mesenteric arteries |
title_full | Cyclooxygenase metabolism mediates vasorelaxation to 2-arachidonoylglycerol (2-AG) in human mesenteric arteries |
title_fullStr | Cyclooxygenase metabolism mediates vasorelaxation to 2-arachidonoylglycerol (2-AG) in human mesenteric arteries |
title_full_unstemmed | Cyclooxygenase metabolism mediates vasorelaxation to 2-arachidonoylglycerol (2-AG) in human mesenteric arteries |
title_short | Cyclooxygenase metabolism mediates vasorelaxation to 2-arachidonoylglycerol (2-AG) in human mesenteric arteries |
title_sort | cyclooxygenase metabolism mediates vasorelaxation to 2-arachidonoylglycerol (2-ag) in human mesenteric arteries |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992009/ https://www.ncbi.nlm.nih.gov/pubmed/24548820 http://dx.doi.org/10.1016/j.phrs.2014.02.001 |
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