Skin-specific mechanisms of body fluid regulation in hypertension

Abstract

Increasing evidence suggests excess skin Na+ accumulation in hypertension; however, the role of skin-specific mechanisms of local Na+/water regulation remains unclear. We investigated the association between measures of sweat and trans-epidermal water loss (TEWL) with Na+ content in the skin ([Na+]skin) and clinical characteristics in consecutive hypertensive patients. We obtained an iontophoretic pilocarpine-induced sweat sample, a skin punch biopsy for chemical analysis, and measures of TEWL from the upper limbs. Serum vascular endothelial growth factor-c (VEGF-c) and a reflectance measure of haemoglobin skin content served as surrogates of skin microvasculature. In our cohort (n = 90; age 21-86 years; females = 49%), sweat composition was independent of sex and BMI. Sweat Na+ concentration ([Na+]sweat) inversely correlated with [K+]sweat and was higher in patients on ACEIs/ARBs (P < 0.05). A positive association was found between [Na+]sweat and [Na+]skin, independent of sex, BMI, estimated Na+ intake and use of ACEi/ARBs (Padjusted = 0.025); both closely correlated with age (P < 0.01). Office DBP, but not SBP, inversely correlated with [Na+]sweat independent of other confounders (Padjusted = 0.03). Total sweat volume and Na+ loss were lower in patients with uncontrolled office BP (Padjusted < 0.005 for both); sweat volume also positively correlated with serum VEGF-c and TEWL. Lower TEWL was paralleled by lower skin haemoglobin content, which increased less after vasodilatory pilocarpine stimulation when BMI was higher (P = 0.010). In conclusion, measures of Na+ and water handling/regulation in the skin were associated with relevant clinical characteristics, systemic Na+ status and blood pressure values, suggesting a potential role of the skin in body-fluid homeostasis and therapeutic targeting of hypertension.

Keywords: homeostasis; hypertension; skin; sodium; sweat; water.

Figure 1. Association of sweat Na ⁺ concentration with skin Na ⁺ and age Association of sweat Na ⁺ concentration with skin Na ⁺ and age

Tissue Na⁺ concentration in the skin and age are positively correlated with sweat Na ⁺ (ρ = 0.302, P = 0.019 and ρ = 0.341, P = 0.002, respectively; linear regression lines are depicted in red). Red X = automatically identified outliers (ROUT = 1%); after their removal, statistics revealed ρ = 0.367, P = 0.001 and ρ = 0.345, P < 0.01, respectively.

Figure 2. Sweat measures in relation to blood pressure values and control.

Sweat Na⁺ concentration is inversely and independently associated with diastolic BP. Office BP control is associated with higher total sweat Na⁺ and total sweat volume (data presented as median [95% CI]).