Microcirculatory Function during Endotoxemia—A Functional Citrulline-Arginine-NO Pathway and NOS3 Complex Is Essential to Maintain the Microcirculation

Competition for the amino acid arginine by endothelial nitric-oxide synthase (NOS3) and (pro-)inflammatory NO-synthase (NOS2) during endotoxemia appears essential in the derangement of the microcirculatory flow. This study investigated the role of NOS2 and NOS3 combined with/without citrulline suppl...

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Autores principales:	Karolina A. P. Wijnands, Dennis M. Meesters, Benjamin Vandendriessche, Jacob J. Briedé, Hans M. H. van Eijk, Peter Brouckaert, Anje Cauwels, Wouter H. Lamers, Martijn Poeze
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	nitric oxide synthase arginine microcirculation endotoxemia citrulline NOS3 Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/59bd5394c46a4b4b917d5de6f091e85c
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spelling	oai:doaj.org-article:59bd5394c46a4b4b917d5de6f091e85c2021-11-11T17:21:28ZMicrocirculatory Function during Endotoxemia—A Functional Citrulline-Arginine-NO Pathway and NOS3 Complex Is Essential to Maintain the Microcirculation10.3390/ijms2221119401422-00671661-6596https://doaj.org/article/59bd5394c46a4b4b917d5de6f091e85c2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11940https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Competition for the amino acid arginine by endothelial nitric-oxide synthase (NOS3) and (pro-)inflammatory NO-synthase (NOS2) during endotoxemia appears essential in the derangement of the microcirculatory flow. This study investigated the role of NOS2 and NOS3 combined with/without citrulline supplementation on the NO-production and microcirculation during endotoxemia. Wildtype (C57BL6/N background; control; <i>n</i> = 36), <i>Nos2</i>-deficient, (<i>n</i> = 40), <i>Nos3</i>-deficient (<i>n</i> = 39) and <i>Nos2/Nos3</i>-deficient mice (<i>n</i> = 42) received a continuous intravenous LPS infusion alone (200 μg total, 18 h) or combined with L-citrulline (37.5 mg, last 6 h). The intestinal microcirculatory flow was measured by side-stream dark field (SDF)-imaging. The jejunal intracellular NO production was quantified by in vivo NO-spin trapping combined with electron spin-resonance (ESR) spectrometry. Amino-acid concentrations were measured by high-performance liquid chromatography (HPLC). LPS infusion decreased plasma arginine concentration in control and <i>Nos3<sup>−/−</sup></i> compared to <i>Nos2<sup>−/−</sup></i> mice. Jejunal NO production and the microcirculation were significantly decreased in control and <i>Nos2<sup>−/−</sup></i> mice after LPS infusion. No beneficial effects of L-citrulline supplementation on microcirculatory flow were found in <i>Nos3<sup>−/−</sup></i> or <i>Nos2<sup>−/−</sup>/Nos3<sup>−/−</sup></i> mice. This study confirms that L-citrulline supplementation enhances de novo arginine synthesis and NO production in mice during endotoxemia with a functional NOS3-enzyme (control and <i>Nos2<sup>−/−</sup></i> mice), as this beneficial effect was absent in <i>Nos3<sup>−/−</sup></i> or <i>Nos2<sup>−/−</sup>/Nos3<sup>−/−</sup></i> mice.Karolina A. P. WijnandsDennis M. MeestersBenjamin VandendriesscheJacob J. BriedéHans M. H. van EijkPeter BrouckaertAnje CauwelsWouter H. LamersMartijn PoezeMDPI AGarticlenitric oxide synthaseargininemicrocirculationendotoxemiacitrullineNOS3Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11940, p 11940 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	nitric oxide synthase arginine microcirculation endotoxemia citrulline NOS3 Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	nitric oxide synthase arginine microcirculation endotoxemia citrulline NOS3 Biology (General) QH301-705.5 Chemistry QD1-999 Karolina A. P. Wijnands Dennis M. Meesters Benjamin Vandendriessche Jacob J. Briedé Hans M. H. van Eijk Peter Brouckaert Anje Cauwels Wouter H. Lamers Martijn Poeze Microcirculatory Function during Endotoxemia—A Functional Citrulline-Arginine-NO Pathway and NOS3 Complex Is Essential to Maintain the Microcirculation
description	Competition for the amino acid arginine by endothelial nitric-oxide synthase (NOS3) and (pro-)inflammatory NO-synthase (NOS2) during endotoxemia appears essential in the derangement of the microcirculatory flow. This study investigated the role of NOS2 and NOS3 combined with/without citrulline supplementation on the NO-production and microcirculation during endotoxemia. Wildtype (C57BL6/N background; control; <i>n</i> = 36), <i>Nos2</i>-deficient, (<i>n</i> = 40), <i>Nos3</i>-deficient (<i>n</i> = 39) and <i>Nos2/Nos3</i>-deficient mice (<i>n</i> = 42) received a continuous intravenous LPS infusion alone (200 μg total, 18 h) or combined with L-citrulline (37.5 mg, last 6 h). The intestinal microcirculatory flow was measured by side-stream dark field (SDF)-imaging. The jejunal intracellular NO production was quantified by in vivo NO-spin trapping combined with electron spin-resonance (ESR) spectrometry. Amino-acid concentrations were measured by high-performance liquid chromatography (HPLC). LPS infusion decreased plasma arginine concentration in control and <i>Nos3<sup>−/−</sup></i> compared to <i>Nos2<sup>−/−</sup></i> mice. Jejunal NO production and the microcirculation were significantly decreased in control and <i>Nos2<sup>−/−</sup></i> mice after LPS infusion. No beneficial effects of L-citrulline supplementation on microcirculatory flow were found in <i>Nos3<sup>−/−</sup></i> or <i>Nos2<sup>−/−</sup>/Nos3<sup>−/−</sup></i> mice. This study confirms that L-citrulline supplementation enhances de novo arginine synthesis and NO production in mice during endotoxemia with a functional NOS3-enzyme (control and <i>Nos2<sup>−/−</sup></i> mice), as this beneficial effect was absent in <i>Nos3<sup>−/−</sup></i> or <i>Nos2<sup>−/−</sup>/Nos3<sup>−/−</sup></i> mice.
format	article
author	Karolina A. P. Wijnands Dennis M. Meesters Benjamin Vandendriessche Jacob J. Briedé Hans M. H. van Eijk Peter Brouckaert Anje Cauwels Wouter H. Lamers Martijn Poeze
author_facet	Karolina A. P. Wijnands Dennis M. Meesters Benjamin Vandendriessche Jacob J. Briedé Hans M. H. van Eijk Peter Brouckaert Anje Cauwels Wouter H. Lamers Martijn Poeze
author_sort	Karolina A. P. Wijnands
title	Microcirculatory Function during Endotoxemia—A Functional Citrulline-Arginine-NO Pathway and NOS3 Complex Is Essential to Maintain the Microcirculation
title_short	Microcirculatory Function during Endotoxemia—A Functional Citrulline-Arginine-NO Pathway and NOS3 Complex Is Essential to Maintain the Microcirculation
title_full	Microcirculatory Function during Endotoxemia—A Functional Citrulline-Arginine-NO Pathway and NOS3 Complex Is Essential to Maintain the Microcirculation
title_fullStr	Microcirculatory Function during Endotoxemia—A Functional Citrulline-Arginine-NO Pathway and NOS3 Complex Is Essential to Maintain the Microcirculation
title_full_unstemmed	Microcirculatory Function during Endotoxemia—A Functional Citrulline-Arginine-NO Pathway and NOS3 Complex Is Essential to Maintain the Microcirculation
title_sort	microcirculatory function during endotoxemia—a functional citrulline-arginine-no pathway and nos3 complex is essential to maintain the microcirculation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/59bd5394c46a4b4b917d5de6f091e85c
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Microcirculatory Function during Endotoxemia—A Functional Citrulline-Arginine-NO Pathway and NOS3 Complex Is Essential to Maintain the Microcirculation

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