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

最近的实验证据表明，与传统观点相反，大量的Na+可以在体内积聚，而不会产生相应的水分保留。这种无水Na+保留是通过无活性Na+储存（即在皮肤中）或通过中性Na+/K+交换（即在骨骼肌中）实现的。虽然这一新概念表明肾外控制容量和血压稳态似乎具有相当大的临床意义，但鉴于心脏病和肾脏疾病以及高血压中全身Na+的紊乱，无水Na+潴留的机制尚不清楚。该建议的重点是身体对皮肤中无活性Na+储存的循环反应。我们假设巨噬细胞是一个移动的钠离子传感器，它被局部间质高渗透压所吸引，并通过VEGF-C（血管内皮生长因子C）分泌到间质空间来调节淋巴管生成，从而间接调节间质Na+含量。这一新的概念表明，免疫系统和全身电解质和液体平衡之间的调节反馈控制系统的一个重要接口，首次提出了饮食中的盐过量，无活性的Na+储存，和慢性炎症反应之间的直接联系。

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.