Sex differences in Skin Sodium Storage in Response to High Salt Diet in Sprague Dawley Rats

Salt‐sensitivity and cardiovascular diseases are more prevalent in men compared to premenopausal women of the same age. Our lab showed that female rats elicit a more rapid natriuretic response to increased dietary salt intake. Beside the well‐established role for kidneys in maintaining blood pressure and sodium balance, skin has emerged as being important in the regulation of sodium homeostasis, but little is known about potential sex differences. Vascular endothelial growth factor‐C (VEGF‐C) contributes to skin sodium storage by enhancing lymphangiogenesis and is generally up regulated by high salt (HS) diet. We hypothesized that females mobilize their skin sodium storage during acclimation to a HS diet. Male and female Sprague Dawley rats (16–18 weeks old) were implanted with telemeters, fed a normal salt (NS, 0.49% NaCl) diet then challenged with a HS (4% NaCl) diet for five days. Three separate groups of male and female rats were euthanized on NS, day 1 HS and day 5 HS. Whole body skins were collected, dried, ashed, and assessed for electrolytes using atomic absorption. In males, skin sodium and water remained unchanged after a 1‐day or a 5‐days challenge with HS. In females, skin sodium storage was decreased on the first day after shifting to HS (79.6 ± 5.7 vs. 99.5 ± 3.1 μmol/g, n=6–7, p<0.05), and returned back to normal levels on day 5 HS (94.9±6.4 μmol/g, n=5). In females, skin water was increased in day 1 and day 5 HS (1.22±0.01 and 1.26±0.03, respectively, vs. 1.11± 0.02 g/g, n=5–7, p<0.05). These changes occurred despite consistent intake of food and water during these protocols. In males only, serum sodium was increased on day 1 HS and day 5 HS (140.8±0.2 and 143.3±1.0, respectively, vs. 137.3±0.8 μmol/ml, n=5–8, p<0.05). Serum osmolality, urea and VEGF‐C were decreased on day 1 HS in males only (urea: 0.42 ± 0.02 vs. 0.28 ± 0.01 mg/ml; VEGF‐C: 215 ± 10 vs. 170 ± 11 pg/ml p<0.05). Serum VEGF‐C was slightly, yet non‐significantly increased in females on day 1 HS. Serum MCP‐1 was increased on day 1 HS only in females (724±40 vs. 575±43 pg/ml, n=6–8, p<0.05). Collectively, these data suggest that female rats acclimate more rapidly to increased dietary sodium intake by mobilizing sodium from skin storage pools. Support or Funding Information Funded by AHA 15POST25090329 to EYG, P01 HL095499 to DMP, K01DK105038 to KH and UAB‐UCSD O'Brien Center