Chu You-Hsiang, Lu Chih-Cherng, Lin Tso-Chou, Tsou Mei-Yung, Hsu Yu-Juei, Ho Shung-Tai, Tung Che-Se, Tseng Ching-Jiunn, Li Min-Hui, Lee Herng-Sheng
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
Institute of Aerospace Medicine, National Defense Medical Center, Taipei, Taiwan.
Am J Hypertens. 2017 Mar 1;30(3):295-303. doi: 10.1093/ajh/hpw161.
Water ingestion induces the osmopressor response, which typically presents as increased total peripheral vascular resistance in young healthy subjects. A previous study has suggested that the RBC membrane receptor is involved in osmopressor stress. Recent studies have indicated nitric oxide synthase phosphorylation in RBCs. However, the main process in signaling pathway activation to elicit such a response is unknown. Herein, we hypothesized that hypo-osmotic stress following water ingestion modulates the eNOS/NO pathway, thereby alternating vascular resistance.
We included 24 young, healthy subjects. Physiological parameters and blood samples were collected at 5 minutes before and 25 and 50 minutes after 50 ml water, 500 ml water, or 500 ml normal saline ingestion. A human receptor tyrosine kinase (RTK) phosphorylation antibody array was used to simultaneously detect and monitor the biological activation pathways in RBCs.
Of the 71 RTKs assayed during the osmopressor response, several RTKs were significantly upregulated, including Tie-2 and Tie-1. Plasma angiopoietin-1 levels significantly increased at 25 minutes after 500 ml water ingestion compared to those at baseline. Simultaneous phosphorylation of Tie-2, Akt, and eNOS in RBCs occurred. RBCs in vitro were stimulated with angiopoietin-1, Tie-2, or 0.8% saline and showed significant increase in Tie-2, Akt, and eNOS phosphorylation upon angiopoietin-1 treatment and enhanced activation upon cotreatment of angiopoietin-1 and 0.8% saline.
The hypo-osmotic stimulus of water ingestion increases angiopoietin-1 secretion and subsequently activates the Tie-2/Akt/eNOS signaling pathway in RBCs, thereby revealing a novel biological mechanism simultaneously occurring with the osmopressor response.
摄入水分会引发渗透压升高反应，在年轻健康受试者中，这种反应通常表现为总外周血管阻力增加。此前一项研究表明，红细胞膜受体参与渗透压应激反应。近期研究显示红细胞中存在一氧化氮合酶磷酸化现象。然而，引发这种反应的信号通路激活的主要过程尚不清楚。在此，我们推测摄入水分后低渗应激会调节内皮型一氧化氮合酶/一氧化氮（eNOS/NO）通路，从而改变血管阻力。
我们纳入了24名年轻健康受试者。在摄入50毫升水、500毫升水或500毫升生理盐水之前5分钟以及之后25分钟和50分钟采集生理参数和血样。使用人受体酪氨酸激酶（RTK）磷酸化抗体芯片同时检测和监测红细胞中的生物激活通路。
在渗透压升高反应过程中检测的71种RTK中，有几种RTK显著上调，包括Tie-2和Tie-1。与基线相比，摄入500毫升水后25分钟时血浆血管生成素-1水平显著升高。红细胞中同时发生了Tie-2、Akt和eNOS的磷酸化。用血管生成素-1、Tie-2或0.8%盐水体外刺激红细胞，血管生成素-1处理后Tie-2、Akt和eNOS磷酸化显著增加，血管生成素-1与0.8%盐水共同处理后激活增强。
摄入水分的低渗刺激会增加血管生成素-1的分泌，随后激活红细胞中的Tie-2/Akt/eNOS信号通路，从而揭示了一种与渗透压升高反应同时发生的新生物学机制。
