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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| Auteurs principaux: | , , , , , , , , |
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| Format: | article |
| Langue: | EN |
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MDPI AG
2021
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| Accès en ligne: | https://doaj.org/article/59bd5394c46a4b4b917d5de6f091e85c |
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| Résumé: | 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. |
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