Department of Surgery, NUTRIM School of Nutrition, Translational Research in Metabolism, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands.
Department of Genetics & Cell Biology, NUTRIM School of Nutrition, Translational Research in Metabolism, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands.
Int J Mol Sci. 2021 Nov 3;22(21):11940. doi: 10.3390/ijms222111940.
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; = 36), -deficient, ( = 40), -deficient ( = 39) and -deficient mice ( = 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 compared to mice. Jejunal NO production and the microcirculation were significantly decreased in control and mice after LPS infusion. No beneficial effects of L-citrulline supplementation on microcirculatory flow were found in or 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 mice), as this beneficial effect was absent in or mice.
在脓毒症中，内皮型一氧化氮合酶（NOS3）和（前）炎症型一氧化氮合酶（NOS2）对精氨酸的竞争似乎对微循环血流紊乱至关重要。本研究旨在探讨 NOS2 和 NOS3 联合/不联合瓜氨酸补充在脓毒症期间的 NO 产生和微循环中的作用。野生型（C57BL6/N 背景；对照组；n = 36）、-缺陷型（n = 40）、-缺陷型（n = 39）和 -缺陷型（n = 42）小鼠分别接受单独持续静脉内 LPS 输注（200 μg 总量，18 h）或联合 L-瓜氨酸（37.5 mg，最后 6 h）输注。通过侧流暗场（SDF）成像测量肠道微循环血流。通过体内 NO 自旋捕获结合电子自旋共振（ESR）光谱法定量测定空肠细胞内的 NO 产生。通过高效液相色谱法（HPLC）测定氨基酸浓度。LPS 输注使对照组和 组小鼠的血浆精氨酸浓度降低。与 组小鼠相比，LPS 输注后对照组和 组小鼠空肠 NO 产生和微循环均明显降低。在 或 组小鼠中，L-瓜氨酸补充对微循环血流没有有益作用。本研究证实，在具有功能性 NOS3 酶的小鼠（对照组和 组）中，L-瓜氨酸补充可增强脓毒症期间的新精氨酸合成和 NO 产生，而在 或 组小鼠中则不存在这种有益作用。
