Figure 3. Relationship among Na⁺ and Cl^– accumulation, water retention, MAP, and unmeasured anions in mice without and with mF4-31c1 treatment.

Relationship between (A) Cl^– accumulation and (B) Na⁺ accumulation in the skin and MAP in control and in mF4-31c1–treated mice fed a HSD. Elevated blood pressure with anti-VEGFR3 treatment was paralleled by increased skin Cl^– content but not with increased skin Na⁺ content. (C) Skin Na⁺ content, skin Cl^– content, and Cl^–-to-Na⁺ ratio in the mice. With HSD, blockade of cutaneous lymphatic capillary density by mF4-31c1 treatment selectively increased skin Cl^– content. (D) Relationship between skin Na⁺ (orange) and Cl^– (blue) accumulation and skin water content in control mice and in mF4-31c1–treated mice fed HSD. Increasing skin Na⁺ or Cl^– content increased skin water. However, the skin Cl^–-to-water ratio was shifted to the right with mF4-31c1 treatment (0.035 ± 0.006 mmol/ml [control HSD] versus 0.050 ± 0.010 mmol/ml [HSD plus mF4-31c1]; P < 0.05), indicating a reduction in the gap between skin Na⁺ and Cl^– content, which represents unmeasured anionic osmolytes. rSKNa⁺, skin Na⁺ content relative to DW; rSKW, skin water content relative to DW. *P < 0.05 versus LSD WT; ^†P < 0.05 versus LSD plus mF4-31c1; ^‡P < 0.05 versus HSD WT.