Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7908
Authors: Manicam, Caroline
Staubitz, Julia
Brochhausen, Christoph
Grus, Franz-Hermann
Pfeiffer, Norbert
Gericke, Adrian
Title: The gatekeepers in the mouse ophthalmic artery: endothelium-dependent mechanisms of cholinergic vasodilation
Online publication date: 7-Oct-2022
Year of first publication: 2016
Language: english
Abstract: Cholinergic regulation of arterial luminal diameter involves intricate network of intercellular communication between the endothelial and smooth muscle cells that is highly dependent on the molecular mediators released by the endothelium. Albeit the well-recognized contribution of nitric oxide (NO) towards vasodilation, the identity of compensatory mechanisms that maintain vasomotor tone when NO synthesis is deranged remain largely unknown in the ophthalmic artery. This is the first study to identify the vasodilatory signalling mechanisms of the ophthalmic artery employing wild type mice. Acetylcholine (ACh)-induced vasodilation was only partially attenuated when NO synthesis was inhibited. Intriguingly, the combined blocking of cytochrome P450 oxygenase (CYP450) and lipoxygenase (LOX), as well as CYP450 and gap junctions, abolished vasodilation; demonstrating that the key compensatory mechanisms comprise arachidonic acid metabolites which, work in concert with gap junctions for downstream signal transmission. Furthermore, the voltage-gated potassium ion channel, Kv1.6, was functionally relevant in mediating vasodilation. Its localization was found exclusively in the smooth muscle. In conclusion, ACh-induced vasodilation of mouse ophthalmic artery is mediated in part by NO and predominantly via arachidonic acid metabolites, with active involvement of gap junctions. Particularly, the Kv1.6 channel represents an attractive therapeutic target in ophthalmopathologies when NO synthesis is compromised.
DDC: 610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
ROR: https://ror.org/023b0x485
DOI: http://doi.org/10.25358/openscience-7908
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY
Information on rights of use: https://creativecommons.org/licenses/by/4.0/
Journal: Scientific reports
6
Pages or article number: Art. 20322
Publisher: Nature Publishing Group
Publisher place: London
Issue date: 2016
ISSN: 2045-2322
Publisher URL: http://dx.doi.org/10.1038/srep20322
Publisher DOI: 10.1038/srep20322
Appears in collections:DFG-OA-Publizieren (2012 - 2017)

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