2006 Fiscal Year Final Research Report Summary
Prostasin as a diagnositc and therapeutic target for salt-sensitive hypertension
| Project/Area Number |
17590834
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Kidney internal medicine
|
|---|
| Research Institution | Kumamoto University |
|---|
Principal Investigator |
KITAMURA Kenichiro Kumamoto University, Faculty of Medical and Pharmaceutical Sciences, Research Associate, 大学院医学薬学研究部, 助手 (10304990)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TOMITA Kimio Kumamoto University, Faculty of Medical and Pharmaceutical Sciences, Professor, 大学院医学薬学研究部, 教授 (40114772)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Keywords | sodium channels / serine protease / prostasin / hypertension |
|---|
| Research Abstract |
Generation of transgenic animal models for prostasin
We developec an adenoviral vector carrying human prostasin cDNA and injected into Wister rats. Rats expressing human prostasin gene showed high blood pressure and hyper aldosteronism. These phenotypes were abolished when the adrenal glands were removed prior to the virus injection, suggesting :hat adrenal gland is responsible for the prostasin mediated hyperaldosteronism.
Application for the diagnosis of salt-sensitive hypertension in humans
We developed prostasin specific RIA system to elucidate the causative role of prostasin in the hypertension in humans. We measured urinary prostasin levels in 121 hypertensive patients and 26 healthy volunteers. We found that urinary prostasin levels had strong positive correlation with urinary aldosterone levels as well as with urinary Na/K ratio which is a marker for the activity of the epithelial sodium channels in the kidney. We also showed a positive correlation between urinary prostasin and plasma aldosterone levels.
Taken together, these findings suggest that urinary prostasin levels might be a good marker for the ENaC activities in the renal tubules. Previously, we demonstrated that aldosterone induces urinary prostasin expression in primary aldosteronism patients. Our current research data indicate the important relationship between aldosterone and prostasin in general hypertensive population.
|
