| Project/Area Number |
16390158
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Applied pharmacology
|
|---|
| Research Institution | Kagawa University |
|---|
Principal Investigator |
ABE Youichi Kagawa University, Faculty of Medicine, Professor, 医学部, 教授 (10047227)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NISHIYAMA Akira Kagawa University, Faculty of Medicine, Assistant, 医学部, 助手 (10325334)
KIMURA Shoji Kagawa University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (30253264)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2005: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥9,900,000 (Direct Cost: ¥9,900,000)
|
|---|
| Keywords | Tubulo-glomerular feedback / Afferent arteriole / Nephropathy / Hypertension / Dahl salt-sensitive rats / ATP / P2 receptor / Suramin / P2受容体 |
|---|
| Research Abstract |
It is speculated that an abnormal tubulo-glomerular feedback (TGF) activity may induce the nephropathy via renal hemodynamic changes. However, there are no useful technique to evaluate the TGF activity. In addition, the transmitters from macula densa cells to afferent arterioles have not been determined yet. We have fortunately solved the first problem by introducing the in vivo dynamic method to evaluate TGF activity. So, the purposes of this project are to determine the transmitter in TGF mechanisms and to develop the new strategy for the treatment of nephropathy by the normalization of TGF activity.
1.Determination of mediators in TGF mechanisms : The renal interstitial concentration of adenosine, ATP and NO metabolites. We observed the positive correlation between TGF-mediated changes in renal vascular resistance and renal interstitial concentration of ATP. Thus, we could pick up ATP for the candidate of TGF mediator.
2.TGF activity in Dahl salt -sensitive (DS) rats : DS rars were ma
… More
intained on low(L:0.3% NaCl) or high salt(H:8% NaCl) diets for 4 weeks. Using in vivo dynamic method described above, superficial afferent arteriolar diameter (AAD) was measured before and during enhanced TGF activity induced by acetazolamide(ACZ). Compared to DS・L rats, DS・H rats showed smaller basal AAD. ACZ significantly decreased, AAD in DS・L rats, but did not change AAD in DS・H rats. Furosemide increased AADs in both rats. These findings indicate an enhancement of TGF activity in DS・H rats.
3.Effect of P2 receptor antagonist, suramin, on TGF activity in DS・H rats : Treatment of suramin significantly increased basal AAD, but AAD did not change during administration of ACD and furosemide, indicating suramin normalized the enhanced TGF activity in DS・H rats.
4.Effects of suramin on blood pressure and urinary excretion of protein : Suramin markedly attenuated the development of hypertension and decreased the urinary protein excretion in DS・H rats.
The result indicates that the development of nephropathy and hypertension is associated with an enhancement of TGF activity in DS・H rats. P2 receptor antagonist should be a good agent for the treatment of nephropathy. Less
|
