The Obligatory Role of the Acetylcholine-Induced Endothelium-Dependent Contraction in Hypertension: Can Arachidonic Acid Resolve this Inflammation?
Endothelium
G-protein
acetylcholine
arachidonic acid metabolites
hypertension
vascular function
Journal
Current pharmaceutical design
ISSN: 1873-4286
Titre abrégé: Curr Pharm Des
Pays: United Arab Emirates
ID NLM: 9602487
Informations de publication
Date de publication:
2020
2020
Historique:
received:
20
01
2020
accepted:
10
04
2020
pubmed:
19
4
2020
medline:
20
1
2021
entrez:
19
4
2020
Statut:
ppublish
Résumé
The endothelium produces many substances that can regulate vascular tone. Acetylcholine is a widely used pharmacological tool to assess endothelial function. In general, acetylcholine binds to G-protein coupled muscarinic receptors that mediate a transient elevation in intracellular, free calcium. This intracellular rise in calcium is responsible for triggering several cellular responses, including the synthesis of nitric oxide, endothelium- derived hyperpolarizing factor, and eicosanoids derived from arachidonic acid. Endothelial arachidonic acid metabolism is also an important signaling pathway for mediating inflammation. Therefore, in conditions with sustained and excessive inflammation such as hypertension, arachidonic acid serves as a substrate for the synthesis of several vasoconstrictive metabolites, predominantly via the cyclooxygenase and lipoxygenase enzymes. Cyclooxygenase and lipoxygenase products can then activate G-protein coupled receptors expressed on vascular smooth muscle cells to causes contractile responses. As a result, acetylcholine-induced contraction due to arachidonic acid is a commonly observed feature of endothelial dysfunction and vascular inflammation in hypertension. In this review, we will critically analyze the literature supporting this concept, as well as address the potential underlying mechanisms, including the possibility that arachidonic acid signaling is diverted away from the synthesis of pro-resolving metabolites in conditions such as hypertension.
Identifiants
pubmed: 32303165
pii: CPD-EPUB-105886
doi: 10.2174/1381612826666200417150121
pmc: PMC7542659
mid: NIHMS1630481
doi:
Substances chimiques
Arachidonic Acid
27YG812J1I
Acetylcholine
N9YNS0M02X
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
3723-3732Subventions
Organisme : NIGMS NIH HHS
ID : R00 GM118885
Pays : United States
Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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