2023 Fiscal Year Final Research Report
Abberent mitochondrial metabolism as a cause of salt-sensitive hypertension
| Project/Area Number |
21K08234
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 53040:Nephrology-related
|
|---|
| Research Institution | International University of Health and Welfare |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2021-04-01 – 2024-03-31
|
| Keywords | 血圧日内変動 / ナトリウムチャネル / ミトコンドリア / 低酸素 / 糖 |
|---|
| Outline of Final Research Achievements |
In the current study, we investigated the impact of hypoxia and high glucose on NCC activation in mDCT cells. Hypoxia induced mitochondrial oxidative stress and activated NCC by increases in its phosphorylation, however, under high glucose, NCC was inactivated. Mito-TEMPO which eliminates mitochondrial oxidative stress reduced NCC activation.
In vivo experiments revealed that intermittent hypoxia activated NCC in the kidney and induced sustained high blood pressure during the sleeping time of mice. When NCC is genetically deleted, the nocturnal blood pressure declined under intermittent hypoxic conditions.
|
| Free Research Field |
腎臓
|
| Academic Significance and Societal Importance of the Research Achievements |
ミトコンドリア機能は腎臓におけるナトリウム再吸収に重要な働きをもち、特に血圧日内変動に影響することが明らかとなった。睡眠時無呼吸症候群ではミトコンドリア由来の酸化ストレスがナトリウムチャネル機能に影響をあたえ、高血圧発症のリスクとなる可能性が考えられる。
一方、尿糖はミトコンドリア機能に悪影響を与えず、ナトリウム再吸収も抑制することが示された。糖尿病の治療において、尿中糖排泄を増加させることは高血圧発症を予防する可能性が考えられる。
|
