Skin-specific mechanisms of body fluid regulation in hypertension

• Published in: Clinical science (1979) Vol. 137; no. 3; pp. 239 - 250
• Main Authors: Chen, Jun Yu, Chew, Khai Syuen, Mary, Sheon, Boder, Philipp, Bagordo, Domenico, Rossi, Gian Paolo, Touyz, Rhian M., Delles, Christian, Rossitto, Giacomo
• Format: Journal Article
• Language: English
• Published: England Portland Press Ltd 01.02.2023
• Subjects: Adult; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Body Fluids - chemistry; Cardiovascular System & Vascular Biology; Endocrinology; Female; Gastrointestinal, Renal & Hepatic Systems; Humans; Hypertension; Middle Aged; Pilocarpine; Sodium; Vascular Endothelial Growth Factor C; Water; Young Adult; skin; sweat; homeostasis; sodium; hypertension; water
• ISSN: 0143-5221; 1470-8736; 1470-8736
• DOI: 10.1042/CS20220609

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.