High-salt diet causes expansion of the lymphatic network and increased lymph flow in skin and muscle of rats

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Item Type:	Article
Title:	High-salt diet causes expansion of the lymphatic network and increased lymph flow in skin and muscle of rats
Creators Name:	Karlsen, T.V., Nikpey, E., Han, J., Reikvam, T., Rakova, N., Castorena-Gonzalez, J.A., Davis, M.J., Titze, J.M., Tenstad, O. and Wiig, H.
Abstract:	OBJECTIVE: A commonly accepted pivotal mechanism in fluid volume and blood pressure regulation is the parallel relationship between body Na+ and extracellular fluid content. Several recent studies have, however, shown that a considerable amount of Na+ can be retained in skin without commensurate water retention. Here, we asked whether a salt accumulation shown to result in VEGF (vascular endothelial growth factor)-C secretion and lymphangiogenesis had any influence on lymphatic function. APPROACH AND RESULTS: By optical imaging of macromolecular tracer washout in skin, we found that salt accumulation resulted in an increase in lymph flow of 26% that was noticeable only after including an overnight recording period. Surprisingly, lymph flow in skeletal muscle recorded with a new positron emission tomography/computed tomography method was also increased after salt exposure. The transcapillary filtration was unaffected by the high-salt diet and deoxycorticosterone-salt treatment, suggesting that the capillary barrier was not influenced by the salt accumulation. A significant reduction in lymph flow after depletion of macrophages/monocytes by clodronate suggests these cells are involved in the observed lymph flow response, together with collecting vessels shown here to enhance their contraction frequency as a response to extracellular Na+. CONCLUSIONS: The observed changes in lymph flow suggest that the lymphatics may influence long-term regulation of tissue fluid balance during salt accumulation by contributing to fluid homeostasis in skin and muscle. Our studies identify lymph clearance as a potential disease-modifying factor that might be targeted in conditions characterized by salt accumulation like chronic kidney disease and salt-sensitive hypertension.
Keywords:	Blood Pressure, Body Water, Extracellular Fluid, Extracellular Matrix, Hypertension, Animals, Mice, Rats
Source:	Arteriosclerosis Thrombosis and Vascular Biology
ISSN:	1079-5642
Publisher:	American Heart Association
Volume:	38
Number:	9
Page Range:	2054-2064
Date:	September 2018
Official Publication:	https://doi.org/10.1161/ATVBAHA.118.311149
PubMed:	View item in PubMed

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