| Project/Area Number |
15590762
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | Fukushima Medical University |
|---|
Principal Investigator |
ISHIBASHI Toshiyuki Fukushima Medical University, School of Medicine, Assistant Professor, 医学部, 助教授 (00223024)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MARUYAMA Yukiko Fukushima Medical University, School of Medicine, Assistant Professor, 医学部, 教授 (90004712)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
|---|
| Keywords | Coronary microcirculation / coronary vasospasm / endothelial injury / endothelin / RhoA / ヘンドセリン / 攣縮 / アセチルコリン |
|---|
| Research Abstract |
Balloon endothelial denudation (ED) was carried out in the epicardial left anterior descending coronary artery (LAD) every 2 weeks, for a total of four times, in 12 pigs. Changes in the denuded site diameter and LAD blood flow caused by acetylcholine (ACh) or serotonin were assessed before each denudation and at 8 weeks. Blood pressure, electrocardiogram (ECG) from the LAD area and LAD blood flow were monitored continuously in conscious and unrestrained pigs. Spontaneous ECG ST depression with a decrease in LAD blood flow appeared at around 2 weeks. In accordance with this, 0.05 μg/kg ACh induced similar ECG and LAD blood flow changes without denuded site narrowing at 8 weeks, suggesting microvascular spasm (Coron Artery Dis 2004 ; 15 : 137-145). In addition, repeated endothelial denudation significantly increased the basal level of plasma concentration of endothelin-1 (ET-1) in coronary sinus at 8weeks compared with control group p<0.01). ET-1 concentration in coronary sinus 1 minute after ACh injection was further augmented in ED group at 4, 6 and 8 weeks compared with the basal level (p<0.01, each). Repeated ED increased the production of reactive oxygen species (ROS) detected by ascorbyl free radical (AFR) and dihydroethidium staining, whereas it was almost prevented by ET-1 type A receptor (ET_A) antagonist. ED induced the decrease of eNOS expression in the microvessels and the downregulation was attenuated in ED+ET_A group. Histological analysis revealed that ET_A antagonist suppressed the downstream vascular remodeling induced by repeated ED. ET-1 plays a crucial role for coronary microvascular spasm and the blockade of ET-1 may be beneficial for treating coronary vasospasm. Furthermore, we found a rapid activation pathway of RhoA which plays an important role in endothelial dysfunction (J Biol Chem 2005 ; 280 : 10182-10188). It remains to elucidate whether this rapid RhoA activation associates with endothelial dysfunction of coronary vasospasm.
|
