Lymphangiogenesis in response to osmotically inactive Na+ storage in the skin

最近的实验证据表明，与传统的观点相反，大量的Na+可以在体内积累，而不需要相应的水分保持。这种无水的Na+保留是通过渗透不活跃的Na+存储(即在皮肤中)或通过渗透中性的Na+/K+交换(即在骨骼肌中)实现的。虽然这一新概念提出的肾外控制容量和血压动态平衡似乎具有相当重要的临床意义，但考虑到心脏和肾脏疾病以及高血压患者全身Na+的紊乱，无水Na+滞留的机制尚不清楚。这项建议侧重于人体对皮肤中渗透活性不活跃的Na+储存的循环反应。我们假设巨噬细胞是一个可移动的渗透感受器，它被局部间质高渗所吸引，通过分泌血管内皮生长因子C来调节淋巴管的生成，从而间接调节间质的Na+含量。这一新概念表明，在调节反馈控制系统中，免疫系统与全身电解质和液体平衡之间存在重要的接口，首次表明饮食过量、渗透活性不活跃的Na+储存与慢性炎症反应之间存在直接联系。

Recent experimental evidence has shown that, in contrast to the traditional view, large amounts of Na+ can be accumulated in the body without commensurate water retention. Such water-free Na+ retention is achieved either by osmotically inactive Na+ storage (i.e. in the skin), or by osmotically neutral Na+/K+ exchange (i.e. in the skeletal muscle). While this novel concept suggesting an extrarenal control of volume and blood pressure homeostasis seems of considerable clinical importance, given the disturbances of whole body Na+ in heart and kidney disease, and hypertension, the mechanisms of water-free Na+ retention are unclear. This proposal focuses on the circlulatory reaction of the body in response to osmotically inactive Na+ storage in the skin. We hypothesize that the macrophage is a mobile osmosensor that is attracted by local interstitial hyperosmolality and indirectly modulates the interstitial Na+ content by regulating lymphangiogenesis via VEGF-C (vascular endothelial growth factor C) secretion into the interstitial space. This novel concept suggests an important interface between the immune system and total body electrolyte and fluid balance in a regulatory feed-back control system, suggesting for the first time a direct link between dietary salt excess, osmotically inactive Na+ storage, and a chronic inflammatory response.