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高盐摄入增加 TRPC3 的表达,并增强高血压患者的 TRPC3 介导的钙离子内流和收缩压。

High-salt intake increases TRPC3 expression and enhances TRPC3-mediated calcium influx and systolic blood pressure in hypertensive patients.

机构信息

Department of Endocrinology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402160, China.

Department of Burn and Plastic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

出版信息

Hypertens Res. 2020 Jul;43(7):679-687. doi: 10.1038/s41440-020-0409-1. Epub 2020 Feb 10.

DOI:10.1038/s41440-020-0409-1
PMID:32037396
Abstract

Enhanced transient receptor potential canonical subtype 3 (TRPC3) expression and TRPC3-mediated calcium influx in monocytes from hypertensive rats and patients are associated with increased blood pressure. Daily salt intake is closely related to hypertension, but the relationship between TRPC3 expression and salt intake has not yet been evaluated in hypertensive patients. Using reverse transcription-polymerase chain reaction, we studied the expression of TRPC3 and TRPC3-related store-operated calcium entry (SOCE) in peripheral blood mononuclear cells (PBMCs) from hypertensive and normotensive control subjects. Measurement of SOCE was performed using the fluorescent dye Fura-2 AM. Participants were divided into a low-salt group (<9 g) and a high-salt group (≥9 g) based on 24-h urinary sodium excretion. Increased TRPC3 mRNA expression levels and SOCE were observed in THP-1 cells after high-NaCl treatment. However, administration of the TRPC3-specific inhibitor Pyr3 significantly decreased the effect. Furthermore, the TRPC3 mRNA expression levels in PBMCs from high-salt intake patients with essential hypertension were significantly higher than those in low-salt intake patients compared with those in normotensive control subjects. We also observed significantly increased TRPC3-mediated SOCE in PBMCs from hypertensive subjects (but not from normotensive control subjects), with calcium concentration correlating with salt intake. More importantly, TRPC3 mRNA levels showed a significant correlation with salt intake and systolic blood pressure in patients with essential hypertension. This study demonstrated, for the first time, that increased TRPC3 mRNA levels are associated with elevated salt intake and systolic blood pressure in hypertensive patients.

摘要

瞬时受体电位经典型亚型 3(TRPC3)表达增强和单核细胞中 TRPC3 介导的钙内流与高血压大鼠和患者的血压升高有关。盐摄入量与高血压密切相关,但高血压患者中 TRPC3 表达与盐摄入量之间的关系尚未得到评估。本研究采用逆转录-聚合酶链反应技术,研究了高血压和正常血压对照组外周血单个核细胞(PBMCs)中 TRPC3 的表达及 TRPC3 相关的钙库操纵性钙内流(SOCE)。使用荧光染料 Fura-2 AM 测量 SOCE。根据 24 小时尿钠排泄量将参与者分为低盐组(<9g)和高盐组(≥9g)。在高 NaCl 处理后,THP-1 细胞中观察到 TRPC3 mRNA 表达水平和 SOCE 增加。然而,TRPC3 特异性抑制剂 Pyr3 的给药显著降低了这种作用。此外,与正常血压对照组相比,高盐摄入的原发性高血压患者 PBMCs 中的 TRPC3 mRNA 表达水平明显更高。我们还观察到高血压患者(而非正常血压对照组)中 TRPC3 介导的 SOCE 显著增加,钙浓度与盐摄入量相关。更重要的是,TRPC3 mRNA 水平与原发性高血压患者的盐摄入量和收缩压呈显著相关性。本研究首次表明,TRPC3 mRNA 水平的增加与高血压患者的盐摄入量增加和收缩压升高有关。

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