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Genetic engineering of lymphangiogenesis in skin does not affect blood pressure in mouse models of salt-sensitive hypertension

Item Type:Article
Title:Genetic engineering of lymphangiogenesis in skin does not affect blood pressure in mouse models of salt-sensitive hypertension
Creators Name:Thowsen, I.M. and Reikvam, T. and Skogstrand, T. and Samuelsson, A.M. and Mueller, D.N. and Tenstad, O. and Alitalo, K. and Karlsen, T. and Wiig, H.
Abstract:BACKGROUND: Recent studies have indicated that sodium storage is influenced by macrophages that secrete VEGF-C (vascular endothelial growth factor) during salt stress thus stimulating lymphangiogenesis, thereby acting as a buffer against increased blood pressure (BP). We aimed to explore the role of dermal lymphatics in BP and sodium homeostasis. Our hypothesis was that mice with reduced dermal lymphatic vessels were more prone to develop salt-sensitive hypertension, and that mice with hyperplastic vessels were protected. METHODS: Mice with either hypoplastic (Chy), absent (K14-VEGFR3 [vascular endothelial growth factor receptor 3]-Ig), or hyperplastic (K14-VEGF-C) dermal lymphatic vessels and littermate controls were given high-salt diet (4% NaCl in the chow), deoxycorticosterone acetate (DOCA)-salt diet and 1% saline to drink or nitric oxide blocker diet L-N(G)-nitro arginine methyl ester (followed by high salt diet). BP was measured by telemetric recording, and tissue sodium content by ion chromatography. RESULTS: In contrast to previous studies, high salt diet did not induce an increase in BP or sodium storage in any of the mouse strains investigated. DOCA-salt, on the other hand, gave an increase in BP in Chy and K14-VEGFR3-Ig not different from their corresponding WT controls. DOCA induced salt storage in skin and muscle, but to the same extent in mice with dysfunctional lymphatic vessels and WT controls. Lymph flow as assessed by tracer washout was not affected by the diet in any of the mouse strains. CONCLUSIONS: Our results suggest that dermal lymphatic vessels are not involved in salt storage or blood pressure regulation in these mouse models of salt-sensitive hypertension.
Keywords:Blood Pressure Regulation, Interstitium, Lymph, Salt, Skin, Animals, Mice
Publisher:American Heart Association
Page Range:2451-2462
Date:November 2022
Additional Information:Copyright © 2022 American Heart Association, Inc.
Official Publication:https://doi.org/10.1161/hypertensionaha.122.19777
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