| Project/Area Number |
04454268
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
KANAIDE Hideo KYUSHU UNIVERSITY,FAC MED,PROFESSOR, 医学部, 教授 (80038851)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIMURA Junji KYUSHU UNIVERSITY,FAC MED,LECTURER, 医学部, 講師 (90237727)
KOBAYASHI Sei KYUSHU UNIVERSITY,FAC MED,ASSOC PROF, 医学部, 助教授 (80225515)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1994: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | vascular smooth muscle / cell calcium / vasoconstriction / vasorelaxation / calcium sensitivity / 血管内皮細胞 / 血管拡張 / 細胞質カルシウム濃度 / エンドセリン受容体 / 細胞カルシウム濃度 / cyclic AMP / 血管〓縮 |
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| Research Abstract |
1.THE PATHOGENESIS OF AN INCREASE IN VASCULAR TONUS.(1) Using RTPCR and fura-2 microfluorometry, the relationships between the levels of the expression of angiotensin (AT) II (type 1) and endothelin (ET) A receptor mRNAs and the physiological responsiveness ([Ca]i) were investigated in rat aortic smooth muscle cells in primary culture. It was found that ATII,PKC and PKA regulate the expression of ATII receptor mRNA,and the increase in mRNA level is accompanied by an increase in physiological responsiveness, and (2) cAMP induces an up-regulation of ETA receptor mRNA and increases the responsiveness to ET-1. (3) Using fura-2-front-surface fluorometry and porcine coronary arterial strips, we found that ET-3 induces vasoconstriction by increasing [Ca]i mainly through Ca-influx from the extracellular space, and that distinct mechanisms of time-dependent modulation of the Ca-sensitivity function in the vasoconstrictor responses to ET-1 and ET-3.
THE DEVELOPMENT OF NEW VASODILATORS.(1) It was found that the main action of papaverine and nicorandil is to decrease changes in [Ca]i and Ca-sensitivity of the contractile apparatus of vascular smooth muscle. Inhibition of both Ca-influx from the extracellular space and Ca-release from the intracellular store plays a major role in the decrease of [Ca]i. (2) In case of nicorandil, the decrease of [Ca]i is due in part to opening of ATP-sensitive K-channels. (3) In rabbit femoral arteries, it was found that LP-805 relaxs smooth musle mainly by activating ATP-sensitive K-channels of smooth muscle cells, and by releasing EDRF from endothelial cells. EDRF induced by LP-805 relaxs smooth muscle not only by decreasing [Ca]i but also decreasing Ca-sensitivity of the contractile apparatus of smooth muscle cells.
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