Project/Area Number |
03557043
|
Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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Allocation Type | Single-year Grants |
Research Field |
Circulatory organs internal medicine
|
Research Institution | KYUSHU UNIVERSITY |
Principal Investigator |
KANAIDE Hideo KYUSHU UNIV, FAC MED, PROFESSOR, 医学部, 教授 (80038851)
|
Co-Investigator(Kenkyū-buntansha) |
NISHIMURA Junji KYUSHU UNIV, FAC MED, LETCURER, 医学部, 講師 (90237727)
KOBAYASHI Sei KYUSHU UNIV, FAC MED, ASSOC PROF, 医学部, 助教授 (80225515)
|
Project Period (FY) |
1991 – 1993
|
Project Status |
Completed (Fiscal Year 1993)
|
Budget Amount *help |
¥11,200,000 (Direct Cost: ¥11,200,000)
Fiscal Year 1993: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1992: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1991: ¥6,400,000 (Direct Cost: ¥6,400,000)
|
Keywords | Fura-2 / Vascular smooth muscle cells / Endothelial cells in situ / Myocardial cells / Ethanol / GTP-binding protein / Endothelin / Endothelium-derived relaxing factor(EDRF) / 血管内皮細胞 / G蛋白質 / EDRF / フラー2 / BCECF / カプトリル / 細胞膜Ca^<++>濃度 |
Research Abstract |
(1) The development of a system for the simultaneous determination of metabolic and functional changes in the heart and blood vessels : A front-surface fluorometer with concentric optical fibers for double-wave length excitation (inner circle quartz fibers) and fluorescence detection (outer circle glass fibers) (CAM OF-2) was successfully and specifically designed and made with the collaboration of Japan Spectroscopic Co., Tokyo, Japan. (2) Using front-surface fluorometry of fura-2-loaded aortic valvular strips, the cytosolic Ca concentration, (Ca)i, of the endothelial cells in situ was firstly and quantitatively recorded. Both endothelin (ET)-1 and ET-3 elevated (Ca)i in the endothelial cells in situ. ET-1 elevated (Ca)i of a peak (the first phase) and sustained (the second phase) type. The second phase was exclusively extracellular Ca-dependent, Ca influx. Pertussis toxin (IAP) markedly inhibited the second phase. Thus, Ca influx induced by ET-1 is regulated by an IAP-sensitive G-protein in the endothelial cells in situ. (3) The effects of ethanol on the contractility of strips of porcine coronary artery, with and without endothelium, and following permeabilization with alpha -toxin, and on aortic valvular endothelial cells in situ were examined. It was found that ethanol contracted the coronaty artery both by increasing (Ca)i and by raising Ca sensitivity of the contractile apparatus, as mediated by GTP-binding protein. When the endothelium was exposed to ethanol, this contraction was prevented, presumably by releasing endothelium-derived relaxing factor (EDRF). (4) Using front-surface fluorometry and BCECF-loaded isolated perfused rat heart, pH changes of the myocardium was successfully recorded during ischemia-reperfusion. It was found that captoril, an angiotensin converting enzyme inhibitor, could partially inhibit the development of acidosis during ischemia.
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