Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, C106

Oral Communications

Skin lymphatic vasculature participates in sodium and blood pressure homeostasis

T. Reikvam1,2, T. Karlsen1, E. Nikpey1, J. Han1, O. Tenstad1, H. Wiig1

1. The Department of Biomedicin, University of Bergen, Bergen, Norway. 2. Norwegian Health Association, Oslo, Norway.

Salt accumulation in the skin leads to lymphangiogenesis. Whether such increase in lymphatic vessels results in enhanced lymph vessel function is unknown. Oppositely, how inability for lymphangiogenesis in skin influence blood pressure regulation is not established. We therefore studied, after salt ingestion, lymphatic function in a rat model shown to induce lymphangiogenesis in skin and blood pressure development in the Chy mouse model that has a mutation resulting in missing lymphatics in skin and lymphoedema. Male Sprague-Dawley rats were given either a high salt diet (chow with 8% salt and 0.9% saline, HSD) for 2 weeks or deoxycorticosterone (100 mg pellet subcutaneously, chow with <0,1% salt and 0,9% saline, DOCA) for 3 weeks. Control rats received low salt diet (chow with <0.1% salt and tap water, LSD) for 2 weeks. Blood pressure was measured with the tail-cuff method. Immunohistochemistry was used to determine the number of lymph vessels in the skin. Na+ accumulation was measured with flame photometry in dry ashed skin. Lymph flow was estimated from tissue clearance of intradermally injected fluorescently labelled albumin, measured with optical imaging. In a separate series of experiments, Chy and wild type (WT) mice were given high salt diet (chow with 4% and 0,9% saline, HSD) for 2 weeks. Blood pressure was measured with 24-hours telemetric recording before the onset and at the end of the high salt diet period. DOCA and HSD rats had a mean blood pressure that was 162±24 mmHg (n=18) and 129±12 mmHg (n=24), respectively, whereas the LSD group had a mean blood pressure of 110±13 mmHg (n=24). The salt content in skin of DOCA and HSD rats was 0,145±0,009 mmol/ml (n=5) and 0,113±0,003 mmol/ml (n=5), respectively, both higher than the 0,093±0,001 in the LSD group (n=6) (p<0.005 for both comparisons). Lymph vessels per mm2 in skin were 167±43 in DOCA (n=3) and 96±23 in HSD (n=3) compared with69±30 in the LSD group(n=3). The removal rate of albumin was higher after salt ingestion, suggesting an increased lymph flow. Thus, the percent of remaining labelled albumin 24-h after injection in skin was estimated to 14.6±1.34% in HSD (n=20) and 20±1.00% in LSD (n=19) groups. Chy mice (n=3) tended to have a higher systolic blood pressure than WT (n=3) before start of the HSD (125±5 mmHg vs. 113±13 mmHg, p>0.05). The HSD resulted in a significant increase in systolic blood pressure during night-time in Chy mice (141±3 mmHg, p<0.05), whereas the pressure in WT was unchanged (119±11mmHg). The heart rate was the same in the two groups after the diet (594±11 BPM vs. 612±34 BPM). Collectively, our data showing that newly formed lymph vessels after salt ingestion are functional and that mice incapable of lymphangiogenesis get salt-induced increase in blood pressure suggest that lymphatics in skin contribute in salt and blood pressure homeostasis.

Where applicable, experiments conform with Society ethical requirements