Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense.
Department of Cardiology, Hospital of Southwest Jutland, Esbjerg.
J Hypertens. 2022 Jan 1;40(1):153-162. doi: 10.1097/HJH.0000000000002990.
The mineralocorticoid receptor antagonist spironolactone lowers blood pressure in patients with resistant hypertension despite antihypertensive treatment with angiotensin-converting inhibitors (ACEi) and angiotensin-II receptor blockers (ARB). In preclinical studies, spironolactone suppresses pro-hypertensive interleukin 17A (IL-17A).
Plasma samples were analysed from a randomized, double-blind placebo-controlled trial with spironolactone given to patients with type 2 diabetes mellitus (T2DM) and resistant hypertension on three antihypertensive drugs. We tested the hypothesis that spironolactone-induced antihypertensive effects are associated with suppression of IL-17A and related cytokines.
Interferon-γ (IFN-γ), IL-17A, tumor necrosis factor-α (TNF-α), IL-6, IL-1β and IL-10 were assessed in plasma with immunoassay in samples before and after 16 weeks of treatment with placebo or spironolactone (12.5-25-50 mg/day).
Spironolactone significantly reduced plasma IFN-γ and IL-6 while IL-17A, TNF-α, IL-1β and IL-10 were unchanged. IL-6 was more sensitive to higher doses of spironolactone. At baseline, serum aldosterone correlated positively with diastolic night blood pressure. Urine albumin/creatinine-ratios correlated positively with plasma IL-6 at baseline. There were no relations between aldosterone and cytokine concentrations at baseline; between cytokine concentration and blood pressure at baseline; and between cytokine concentration decrease and blood pressure decrease, except for IFN-γ, after treatment. The spironolactone-induced elevation in plasma potassium related inversely to blood pressure but not to changes in cytokines. In macrophages in vitro, spironolactone suppressed lipopolysaccharide (LPS)-induced TNF-α, IL-6, IL-1β and IL-10 levels.
The antihypertensive action of spironolactone in resistant hypertensive patients is associated with suppressed IFN-γ and IL-6 and not IL-17A. Spironolactone exerts anti-inflammatory actions in vivo on macrophages and T-cells.
尽管使用血管紧张素转换酶抑制剂（ACEi）和血管紧张素 II 受体阻滞剂（ARB）进行了抗高血压治疗，醛固酮受体拮抗剂螺内酯仍可降低耐药性高血压患者的血压。在临床前研究中，螺内酯抑制促高血压白介素 17A（IL-17A）。
分析了一项随机、双盲安慰剂对照试验的血浆样本，该试验将螺内酯用于 3 种抗高血压药物治疗的 2 型糖尿病（T2DM）和耐药性高血压患者。我们检验了这样一个假设，即螺内酯引起的降压作用与抑制 IL-17A 和相关细胞因子有关。
使用免疫测定法评估治疗前和治疗 16 周后安慰剂或螺内酯（12.5-25-50mg/天）治疗时的血浆中干扰素-γ（IFN-γ）、IL-17A、肿瘤坏死因子-α（TNF-α）、IL-6、IL-1β和 IL-10。
螺内酯显著降低了血浆 IFN-γ 和 IL-6，而 IL-17A、TNF-α、IL-1β和 IL-10 不变。IL-6 对螺内酯的高剂量更敏感。在基线时，血清醛固酮与舒张压夜间血压呈正相关。尿白蛋白/肌酐比值与基线时的血浆 IL-6 呈正相关。在基线时，醛固酮与细胞因子浓度之间没有关系；细胞因子浓度与基线时的血压之间没有关系；细胞因子浓度下降与血压下降之间没有关系，除了治疗后 IFN-γ。螺内酯引起的血浆钾升高与血压呈负相关，但与细胞因子变化无关。在体外巨噬细胞中，螺内酯抑制脂多糖（LPS）诱导的 TNF-α、IL-6、IL-1β和 IL-10 水平。
螺内酯在耐药性高血压患者中的降压作用与抑制 IFN-γ 和 IL-6 而不是 IL-17A 有关。螺内酯在体内对巨噬细胞和 T 细胞具有抗炎作用。
