Contractile activity in the lymphatic vasculature is essential for maintaining fluid balance within organs and tissues. However, the mechanisms by which collecting lymphatics adapt to changes in fluid load and how these adaptations influence lymphatic contractile activity are unknown. Here we report a model of lymphatic injury based on the ligation of one of two parallel lymphatic vessels in the hind limb of sheep and the evaluation of structural and functional changes in the intact, remodelling lymphatic vessel over a 42-day period. We show that the remodelled lymphatic vessel displayed increasing intrinsic contractile frequency, force generation and vessel compliance, as well as decreasing flow-mediated contractile inhibition via the enzyme endothelial nitric oxide synthase. A computational model of a chain of lymphatic contractile segments incorporating these adaptations predicted increases in the flow-generation capacity of the remodelled vessel at the expense of normal mitochondrial function and elevated oxidative stress within the lymphatic muscle. Our findings may inform interventions for mitigating lymphatic muscle fatigue in patients with dysfunctional lymphatics.

中文翻译：

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羊后肢淋巴损伤后的淋巴重塑。

淋巴管系统中的收缩活动对于维持器官和组织内的液体平衡至关重要。然而，尚不清楚收集淋巴管适应血液负荷变化的机制以及这些适应如何影响淋巴收缩活动的机制。在这里，我们报告了一种基于绵羊后肢中两条平行淋巴管之一的结扎和在42天的时间内对完整，重塑的淋巴管的结构和功能变化进行评估的淋巴损伤模型。我们显示，改建的淋巴管显示出增加的固有收缩频率，力的产生和血管的顺应性，以及通过酶内皮一氧化氮合酶减少流介导的收缩抑制作用。结合了这些适应性的一系列淋巴收缩节段的计算模型预测了重构血管的血流生成能力的增加，但以正常线粒体功能和淋巴肌内氧化应激的增加为代价。我们的发现可能为缓解功能障碍性淋巴瘤患者的淋巴肌肉疲劳提供了依据。