Compensatory Vasodilator Mechanisms in the Ophthalmic Artery of Endothelial Nitric Oxide Synthase Gene Knockout Mice

Abstract Nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) plays an important role in the maintenance of ocular vascular homeostasis. Therefore, perturbations in vascular NO synthesis have been implicated in the pathogenesis of several ocular diseases. We recently reported that...

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Autores principales:	Caroline Manicam, Natalja Ginter, Huige Li, Ning Xia, Evgeny Goloborodko, Jenia Kouchek Zadeh, Aytan Musayeva, Norbert Pfeiffer, Adrian Gericke
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/06285f9a5ab14f8f926e07fd906afa12
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spelling	oai:doaj.org-article:06285f9a5ab14f8f926e07fd906afa122021-12-02T15:05:50ZCompensatory Vasodilator Mechanisms in the Ophthalmic Artery of Endothelial Nitric Oxide Synthase Gene Knockout Mice10.1038/s41598-017-07768-72045-2322https://doaj.org/article/06285f9a5ab14f8f926e07fd906afa122017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07768-7https://doaj.org/toc/2045-2322Abstract Nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) plays an important role in the maintenance of ocular vascular homeostasis. Therefore, perturbations in vascular NO synthesis have been implicated in the pathogenesis of several ocular diseases. We recently reported that eNOS contributes significantly to vasodilation of the mouse ophthalmic artery. Interestingly, dilatory responses were also retained in eNOS gene-deficient mice (eNOS−/−), indicating inherent endothelial adaptive mechanism(s) that act as back-up systems in chronic absence of eNOS to preserve vasorelaxation. Thus, this study endeavoured to identify the compensatory mechanism(s) in the ophthalmic artery of eNOS−/− mice employing isolated arterial segments and pharmacological inhibitors in vitro. Endothelium removal virtually abolished acetylcholine (ACh)-induced vasodilation, suggesting an obligatory involvement of the endothelium in cholinergic control of vascular tone. However, non-NOS and non-cyclooxygenase components compensate for eNOS deficiency via endothelium-derived hyperpolarizing factors (EDHFs). Notably, arachidonic acid-derived metabolites of the 12-lipoxygenase pathway were key mediators in activating the inwardly rectifying potassium channels to compensate for chronic lack of eNOS. Conclusively, endothelium-dependent cholinergic responses of the ophthalmic artery in the eNOS−/− mice are largely preserved and, this vascular bed has the ability to compensate for the loss of normal vasodilator responses solely via EDHFs.Caroline ManicamNatalja GinterHuige LiNing XiaEvgeny GoloborodkoJenia Kouchek ZadehAytan MusayevaNorbert PfeifferAdrian GerickeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Caroline Manicam Natalja Ginter Huige Li Ning Xia Evgeny Goloborodko Jenia Kouchek Zadeh Aytan Musayeva Norbert Pfeiffer Adrian Gericke Compensatory Vasodilator Mechanisms in the Ophthalmic Artery of Endothelial Nitric Oxide Synthase Gene Knockout Mice
description	Abstract Nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) plays an important role in the maintenance of ocular vascular homeostasis. Therefore, perturbations in vascular NO synthesis have been implicated in the pathogenesis of several ocular diseases. We recently reported that eNOS contributes significantly to vasodilation of the mouse ophthalmic artery. Interestingly, dilatory responses were also retained in eNOS gene-deficient mice (eNOS−/−), indicating inherent endothelial adaptive mechanism(s) that act as back-up systems in chronic absence of eNOS to preserve vasorelaxation. Thus, this study endeavoured to identify the compensatory mechanism(s) in the ophthalmic artery of eNOS−/− mice employing isolated arterial segments and pharmacological inhibitors in vitro. Endothelium removal virtually abolished acetylcholine (ACh)-induced vasodilation, suggesting an obligatory involvement of the endothelium in cholinergic control of vascular tone. However, non-NOS and non-cyclooxygenase components compensate for eNOS deficiency via endothelium-derived hyperpolarizing factors (EDHFs). Notably, arachidonic acid-derived metabolites of the 12-lipoxygenase pathway were key mediators in activating the inwardly rectifying potassium channels to compensate for chronic lack of eNOS. Conclusively, endothelium-dependent cholinergic responses of the ophthalmic artery in the eNOS−/− mice are largely preserved and, this vascular bed has the ability to compensate for the loss of normal vasodilator responses solely via EDHFs.
format	article
author	Caroline Manicam Natalja Ginter Huige Li Ning Xia Evgeny Goloborodko Jenia Kouchek Zadeh Aytan Musayeva Norbert Pfeiffer Adrian Gericke
author_facet	Caroline Manicam Natalja Ginter Huige Li Ning Xia Evgeny Goloborodko Jenia Kouchek Zadeh Aytan Musayeva Norbert Pfeiffer Adrian Gericke
author_sort	Caroline Manicam
title	Compensatory Vasodilator Mechanisms in the Ophthalmic Artery of Endothelial Nitric Oxide Synthase Gene Knockout Mice
title_short	Compensatory Vasodilator Mechanisms in the Ophthalmic Artery of Endothelial Nitric Oxide Synthase Gene Knockout Mice
title_full	Compensatory Vasodilator Mechanisms in the Ophthalmic Artery of Endothelial Nitric Oxide Synthase Gene Knockout Mice
title_fullStr	Compensatory Vasodilator Mechanisms in the Ophthalmic Artery of Endothelial Nitric Oxide Synthase Gene Knockout Mice
title_full_unstemmed	Compensatory Vasodilator Mechanisms in the Ophthalmic Artery of Endothelial Nitric Oxide Synthase Gene Knockout Mice
title_sort	compensatory vasodilator mechanisms in the ophthalmic artery of endothelial nitric oxide synthase gene knockout mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/06285f9a5ab14f8f926e07fd906afa12
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Compensatory Vasodilator Mechanisms in the Ophthalmic Artery of Endothelial Nitric Oxide Synthase Gene Knockout Mice

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