Water and Electrolyte Content in Hypertension in the Skin (WHYSKI) in Primary Aldosteronism.

IF 6.9 1区医学 Q1 PERIPHERAL VASCULAR DISEASE Hypertension Pub Date : 2024-12-01 Epub Date: 2024-10-02 DOI:10.1161/HYPERTENSIONAHA.124.23700

Francesca Torresan, Federico B Rossi, Ilaria Caputo, Sofia Zanin, Brasilina Caroccia, Andrea Mattarei, Michela Paccagnella, Eva Kohlscheen, Teresa M Seccia, Maurizio Iacobone, Gian-Paolo Rossi

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Abstract

Background: Primary aldosteronism (PA), the most common curable salt-dependent form of arterial hypertension, features renal K⁺ loss and enhanced Na⁺ reabsorption. We investigated whether the electrolyte, water, and TonEBP (tonicity-responsive enhancer binding protein)/NFAT5 (nuclear factor of activated T cells 5) content is altered in the skin of patients with PA and corrected by surgical cure.

Methods: We obtained skin biopsies from 80 subjects: 49 consecutive patients with PA, optimally treated with a mineralocorticoid receptor antagonist; 6 essential hypertensives; and 25 normotensive controls. We measured Na⁺, K⁺, water content with atomic absorption spectroscopy after ashing, and NFAT5 mRNA with digital droplet polymerase chain reaction. The patients with PA were retested after adrenalectomy.

Results: We discovered a higher dry weight of the skin biopsy specimen at surgery than at follow-up (P<0.001) and a direct correlation with electrolyte and water content (all P<0.01), indicating the need for dry weight adjustment of electrolyte and water data. Surgical cure of PA markedly increased skin dry weight-adjusted K⁺ (from 1.14±0.1 to 2.81±0.27 µg/mg; P<0.001) and water content (from 2.92±1.4 to 3.85±0.23 mg/mg; P<0.001), but left dry weight-adjusted skin Na⁺ content unaffected. In patients with PA at baseline, NFAT5 mRNA was higher (P=0.031) than in normotensive controls and decreased after surgery (P=0.035).

Conclusions: Despite mineralocorticoid receptor antagonist treatment ensuring normokalemia, the patients with PA had a skin cell K⁺ depletion that was corrected by adrenalectomy. The activated NFAT5/TonEBP pathway during mineralocorticoid receptor antagonist administration suggests enhanced skin Na⁺ lymphatic drainage and can explain the lack of overt skin Na⁺ accumulation in patients with PA. Its deactivation after surgical cure can account for the lack of skin Na⁺ decrease postadrenalectomy.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06090617.

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原发性醛固酮增多症皮肤高血压中的水和电解质含量 (WHYSKI)。

背景：原发性醛固酮增多症（PA）是最常见的可治愈的盐依赖性动脉高血压，其特点是肾脏K+丢失和Na+重吸收增强。我们研究了 PA 患者皮肤中的电解质、水和 TonEBP（强直反应性增强子结合蛋白）/NFAT5（活化 T 细胞核因子 5）含量是否会发生改变，并通过手术治愈进行纠正：方法：我们采集了 80 名受试者的皮肤活检样本：方法：我们采集了 80 名受试者的皮肤活检样本：49 名连续接受矿物质皮质激素受体拮抗剂最佳治疗的 PA 患者、6 名本质性高血压患者和 25 名血压正常的对照组患者。我们在灰化后用原子吸收光谱测量了 Na+、K+ 和水分含量，并用数字液滴聚合酶链反应测量了 NFAT5 mRNA。肾上腺切除术后对 PA 患者进行了复测：我们发现手术时皮肤活检标本的干重高于随访时的干重（PP+ 从 1.14±0.1 µg/mg 升至 2.81±0.27 µg/mg；PP+ 的含量未受影响）。在 PA 患者中，NFAT5 mRNA 比正常血压对照组高（P=0.031），手术后降低（P=0.035）：结论：尽管矿皮质激素受体拮抗剂治疗确保了正常血钾，但 PA 患者的皮肤细胞 K+ 缺乏仍可通过肾上腺切除术得到纠正。在使用矿物质皮质激素受体拮抗剂期间，NFAT5/TonEBP通路被激活，这表明皮肤Na+淋巴引流增强，可以解释PA患者没有明显的皮肤Na+积聚。其在手术治愈后失活可解释肾上腺切除术后皮肤Na+减少的原因：URL：https://www.clinicaltrials.gov；唯一标识符：NCT06090617。

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来源期刊

Hypertension 医学-外周血管病

CiteScore

15.90

自引率

4.80%

发文量

1006

审稿时长

1 months

期刊介绍： Hypertension presents top-tier articles on high blood pressure in each monthly release. These articles delve into basic science, clinical treatment, and prevention of hypertension and associated cardiovascular, metabolic, and renal conditions. Renowned for their lasting significance, these papers contribute to advancing our understanding and management of hypertension-related issues.

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