Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, Chongqing Institute of Hypertension, Chongqing, China.
Department of Plastic & Cosmetic Surgery, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China.
Am J Hypertens. 2024 Aug 14;37(9):708-716. doi: 10.1093/ajh/hpae068.
The renal proximal tubule (RPT) plays a pivotal role in regulating sodium reabsorption and thus blood pressure (BP). Transient receptor potential ankyrin 1 (TRPA1) has been reported to protect against renal injury by modulating mitochondrial function. We hypothesize that the activation of TRPA1 by its agonist cinnamaldehyde may mitigate high-salt intake-induced hypertension by inhibiting urinary sodium reabsorption through restoration of renal tubular epithelial mitochondrial function.
Trpa1-deficient (Trpa1-/-) mice and wild-type (WT) mice were fed standard laboratory chow [normal diet (ND) group, 0.4% salt], standard laboratory chow with 8% salt [high-salt diet (HS) group], or standard laboratory chow with 8% salt plus 0.015% cinnamaldehyde [high-salt plus cinnamaldehyde diet (HSC) group] for 6 months. Urinary sodium excretion, reactive oxygen species (ROS) production, mitochondrial function, and the expression of sodium hydrogen exchanger isoform 3 (NHE3) and Na+/K+-ATPase of RPTs were determined.
Chronic dietary cinnamaldehyde supplementation reduced tail systolic BP and 24-hour ambulatory arterial pressure in HS-fed WT mice. Compared with the mice fed HS, cinnamaldehyde supplementation significantly increased urinary sodium excretion, inhibited excess ROS production, and alleviated mitochondrial dysfunction of RPTs in WT mice. However, these effects of cinnamaldehyde were absent in Trpa1-/- mice. Furthermore, chronic dietary cinnamaldehyde supplementation blunted HS-induced upregulation of NHE3 and Na+/K+-ATPase in WT mice but not Trpa1-/- mice.
The present study demonstrated that chronic activation of Trpa1 attenuates HS-induced hypertension by inhibiting urinary sodium reabsorption through restoring renal tubular epithelial mitochondrial function. Renal TRPA1 may be a potential target for the management of excessive dietary salt intake-associated hypertension.
肾近端小管 (RPT) 在调节钠重吸收进而调节血压 (BP) 方面发挥着关键作用。已有研究报道，瞬时受体电位锚蛋白 1 (TRPA1) 通过调节线粒体功能来保护肾脏免受损伤。我们假设，其激动剂肉桂醛激活 TRPA1 可能通过恢复肾小管上皮细胞线粒体功能抑制尿钠重吸收，从而减轻高盐摄入引起的高血压。
TRPA1 缺陷型 (Trpa1-/-) 小鼠和野生型 (WT) 小鼠分别喂食标准实验室饲料[正常饮食 (ND) 组，0.4%盐]、标准实验室饲料加 8%盐[高盐饮食 (HS) 组]或标准实验室饲料加 8%盐加 0.015%肉桂醛[高盐加肉桂醛饮食 (HSC) 组]6 个月。测定尿钠排泄量、活性氧 (ROS) 生成、线粒体功能以及肾近端小管 NHE3 和 Na+/K+-ATP 酶的表达。
慢性膳食肉桂醛补充可降低 HS 喂养 WT 小鼠的尾动脉收缩压和 24 小时动态动脉血压。与 HS 喂养的小鼠相比，肉桂醛补充显著增加了尿钠排泄，抑制了过量的 ROS 生成，并缓解了 WT 小鼠 RPT 的线粒体功能障碍。然而，肉桂醛在 Trpa1-/-小鼠中没有这些作用。此外，慢性膳食肉桂醛补充可减弱 HS 诱导的 WT 小鼠 NHE3 和 Na+/K+-ATP 酶的上调，但在 Trpa1-/-小鼠中没有。
本研究表明，慢性激活 TRPA1 通过恢复肾小管上皮细胞线粒体功能抑制尿钠重吸收，从而减轻 HS 引起的高血压。肾脏 TRPA1 可能是管理过量膳食盐摄入相关高血压的潜在靶点。
