Salt-sensitive hypertension and vascular dysfunction

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09724
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: International University of Health and Welfare
• Principal Investigator: Shimosawa Tatsuo 国際医療福祉大学, 医学部, 主任教授 (90231365)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 食塩感受性高血圧 / 血管内皮機能 / 遠位尿細管 / ナトリウム / 酸化ストレス

Outline of Final Research Achievements

To investigate the cause of salt sensitivity, we used low-dose L-NAME. A high salt diet increased the circulating blood volume regardless of the L-NAME-treatment for the first 24 hours but it returned to the baseline in nontreated group. In contrast to the blood volume changes, blood pressure was higher only in the L-NAME-treated group. An increase in natriuresis was observed after treatment with hydrochlorothiazide, but not amiloride, and this change was observed in parallel with increases in phosphorylated NCC. A change in blood pressure was not observed in the L-NAME-treated NCC-deficient mice fed a high salt diet. Moreover, L-NAME-induced NCC activation was demonstrated in mDCT cells. The effect of L-NAME on phosphorylated NCC was blocked by both the SPAK inhibitor and TEMPO. TEMPO also attenuated salt-induced hypertension. In conclusion, even slightly impaired NO may be important in salt sensitivity.

Free Research Field

高血圧

Academic Significance and Societal Importance of the Research Achievements

高齢者、糖尿病、動脈硬化疾患など食塩感受性を呈しやすい病態に血管拡張機能低下が関与することを示唆するものである。
予後不良の食塩感受性高血圧の治療には腎臓ならびに酸化ストレス、血管反応性を考慮することが必要である。