RELATIONSHIP BETWEEN LYMPHANGIOGENESIS, TISSUE MACROPHAGES EXPRESSION AND SUBCUTANEOUS SODIUM CONCENTRATION: EFFECTS OF HYPERSODIC AND HYPOSODIC DIET IN A NORMOTENSIVE RAT. (June 2018) - Verzicco, I.
Abstract : Objective: Salt retention is a condition associated with a mild inflammatory state. Recent researches pointed out the skin as central regulator of sodium balance besides the traditional "nephrocentric view". Hypertonic skin sodium storage is associated with osmotical and immunological disregulation expressed by activation of tonicity-sensing pathways in macrophages, stimulation of lymphangiogenesis facilitating skin sodium clearance. The aim of this study is to evaluate in a model of normotensive rat the effect of two different dietary sodium regimens on the interstitial sodium levels, lymphangiogenesis and tissue macrophages expression. Design and method: Two groups of normotensive rats (Wistar Kyoto) were fed for three weeks with two different dietary regimens, respectively, High Salt Diet (HSD, NaCl 8%) and Low Salt Diet (LSD, NaCl 0, 08%). Interstitial subcutaneous sodium concentration was measured by microdialysis procedure. Tissue evaluation of Macrophage component, endothelial and lymphatic capillary density was evaluated by Immunohystochemistry analysis. Macrophage was detected by anti CD-68 antibodies, vascular endothelial structures revealed by von Willebrand Factor antibodies and the lymphatic elements by Podoplanin (D2-40) antibodies. Results: There was no significant difference between interstitial sodium concentration and sodium plasma levels (144mmol/L vs 146 mmol/L). Hystological differences were found in the two groups (HSD and LSD): measurements of lymphatic podoplanin (D2-40) component and endothelial structures were different (average of vessels number per mm2 (D2-40: HSD 3, 90 vs LSD 2, 08; von-Willebrand: HSD 6, 04 vs LSD 4, 62). Similarly, macrophage population average of number of cells per mm2 area was higher in HSD (CD 68+: 6, 90) vs LSD (CD68+:5, 65). Conclusions: The effect of an high salt dietary intake bursts an inflammatory response supporting the idea that interstitial tonicity variations may be related to macrophage activation and, consequently, lympho-endothelial expression. HSD did not lead to any difference in interstitial sodium concentration assuming an adeguate ability in drainage of skin sodium excess in a model of normotensive rat.