| Project/Area Number |
11670658
|
|---|
| 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 | YAMAGATA UNIVERSITY |
|---|
Principal Investigator |
KATANO Yumi YAMAGATA UNIVERSITY, SCHOOL OF MEDICINE, PROFESSOR., 医学部, 教授 (70018696)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ISHIHATA Akira YAMAGATA UNIVERSITY, SCHOOL OF MEDICINE, INSTRUCTOR., 医学部, 助手 (40232326)
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥2,700,000 (Direct Cost: ¥2,700,000)
|
|---|
| Keywords | age-related changes / nitric oxide / PGI_2 / endothelial cell / PGI synthase / PGI_2 receptor / COX-1 / coronary flow / 血管内皮細胞 / プロスタサイクリン(PGI_2) / -酸化窒素(NO) / PGI_2合成酵素 / Fischer 344 rat / 老化 / プロスタサイクリン / L-アルギニン トランスポーター / 冠血管 / アンジオテンシンII / Fischer 344 ラット |
|---|
| Research Abstract |
The incidence of cardiovascular disorder due to coronary artery disease increases with advansing age. Endothelium plays an important role in regulating vascular tone and in maintaining the cardiovascular function. We previously demonstrated that several vasoconstricting peptides such as angiotensin II and endothelin-1 stimulated the release of NO in the coronary artery of young rat, but the production was attenuated in the aged rat. This impaired production of NO may contribute to the greater constrictor effect of the vasoconstrictors in the aged rat. In contrast, the vasoconstrictors stimulated the release of PGI_2 to a much greater extent in aged rats than in young rats. It might be possible that aged endothelial cells could produce PGI_2 as a compensation-mechanism for reduced production of NO.
To elucidate the mechanism of age-related changes in the release of NO and PGI_2, We examined the age-related changes in the expression of enzymes responsible for the synthesis of NO and PGI_2 and PGI_2 receptors to reveal the mechanism of regulation of PGI_2 production. Aorta and hearts were isolated from 3- and 27- months old Fischer 344 rats. Hearts were perfused with constant pressure (75 cmH_2O) at 37℃. Changes in the coronary flow were measured with a flow meter. 6-keto-PGF_<1α> in the coronary effluent was measured with EIA.Changes in the expression of PGI_2 receptors, NO and PGI synthase and cyclooxygenase-1 (COX-1) were quantified by real-time PCR and Western blot analysis. Release of PGI_2 into the effluent was greater in the aged rat than young rat. There was no age-related difference in the amount of PGI_2 receptor. Expression of COX-1 and PGI synthase was increased in the aged rat. These increases in COX-1 and PGI synthase may be responsible for the increased production of PGI_2 in the aged rat coronary artery. It is not yet clarified whether the expressions of NO syntase and arginine transportor change with aging.
|
