2005 Fiscal Year Final Research Report Summary
Non-genomic action of aldosterone.
| Project/Area Number |
16590914
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Endocrinology
|
|---|
| Research Institution | Tokyo women's Medical University |
|---|
Principal Investigator |
TANABE Akiyo Tokyo women's Medical University, Medical department, Clinical associate, 医学部, 助手 (00236655)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NARUSE Mitsuhide clinical research institute of endocrine and metabolic disease, Kyoto medical center, Division of endocrinology, Director, 臨床研究センター, 部長 (40120018)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Keywords | Aldosterone / Genomic action / non-genomic action / Mineralocorticoid |
|---|
| Research Abstract |
In order to elucidate both the genomic and non-genomic actions of aldosterone (Aldo.), we have investigated 1) the cardioprotective effects of spironolactone (SPRL) in chronically aldosterone-infused Wistar rats, 2) the cardio- and renoprotective effects of low dose SPRL or selective Aldo. blocker eplerenone (EPLR) in SHR-SP, and 3) the effects of Aldo. on the oxidative stress in vitro in cultures endothelial cells. There was a significant increase in the cardiac mRNA expression of collagen type 1 and 3, and BNP and renal mRNA expression of collagen type 1 and 3 in Aldo-treated rats. SPRL suppressed almost completely the cardiac and renal mRNA expression induced by Aldo.. Although Aldo. did not affect the expression of NADPH components, SPRL significantly suppressed the expression of all its components. In SHR-SP, although the cardiac collagen mRNA expression was significantly decreased by low dose SPRL, both of BNP and ET-1 mRNA expression was increased. By contrast, cardiac collagen and BNP mRNA expression were significantly decreased by low dose EPLR, while ET-1 mRNA did not show any increase. In the endothelial cells, Aldo. suppressed NOX-4 mRNA expression in a dose- and time-dependent manner after incubation for 2 hours or more. Taken together all these data obtained both in vivo and in vitro, it is suggested that most of the actions of aldosterone leading to the target organ damage are mainly mediated through its genomic action, although non-genomic action is not completely excluded.
|
