| Project/Area Number |
05454691
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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 |
Biomedical engineering/Biological material science
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| Research Institution | University of Tsukuba |
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Principal Investigator |
OHSHIMA Norio Inst.of Basic Med.Sci.Univ.of Tsukuba Professor, 基礎医学系, 教授 (50015971)
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| Co-Investigator(Kenkyū-buntansha) |
OOKAWA Keiko Inst.of Basic Med.Sci.Univ.of Tsukuba Assist.Prof., 基礎医学系, 講師 (30251052)
YANAGI Kennichi Inst.of Basic Med.Sci.Univ.of Tsukuba Assist.Prof., 基礎医学系, 講師 (70239797)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥6,200,000 (Direct Cost: ¥6,200,000)
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| Keywords | myocardium / microcirculatin / calcitonine gene related protein / endothelin-1 / Langendorf's perfusion / 心筋、 / 微小循環、 / エンドセリン、 / カルシトニン遺伝子関連ペプチド / 冠循環 / 血行力学 |
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| Research Abstract |
Calcitonin gene-related peptide (CGRP), known as a potent vasodilator and a nervemediated vasoactive peptide, is a candidate for a possible physiological antagonist of endothelin-1 (ET-1). Thus, we investigated the pharmacological interactions between ET-1 and CGRP with a special emphasis on the microvascular hemodynamics and the energy-related metabolites in the myocardium.
The isolated rat hearts were perfused at a constant flow rate with an oxygenated Krebs-Ringer solution in the Langendorff's perfusion preparation. An intracoronary bolus injection of CGRP into the isolated rat beating heart dose-dependently decreased the coronary perfusion pressure (CPP) precontracted by ET-1 (30 pmole). Vasodilating action of CGRP was about three orders of magnitude potent than that of nitroglycerin and two orders potent than that of isobutylmethylxanthine (IBMX). Ed50 value ET-1 and CGRP was almost comparable in order. Microvascular blood flow was also visualized in the anterior epicardium of the
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left ventricle by means of an intravital fluorescence microscope system. The CGRP (100 pmole) -induced vasodilation of the small-sized arterioles (10-40, um in diameter) was also confirmed by small-sized arterioles (10-40, um in diameter) was also confirmed by the direct intravital microscopic observation (relaxation ratio was 47.1<plus-minus>5.4% (mean<plus-minus>SE,n
Energy-related metabolite contents in the myocardium were measured by means of 31P-nuclear magnetic resonance (31P-NMR) spectroscopy. After ET-1 (30 pmole) plus vehicle administration, high-energy phosphates (phosphocreatine (PCr), ATP) were markedly reduced (44<plus-minus>7%, 17<plus-minus>5%), while myocardial pH decreased by -0.19<plus-minus>0.09. These anaerobic changes in the myocardium as well as macrohemodynamic alterations (increases in CPP,decrease in dP/dt etc.) induced by ET-1 was markedly protected ; 1 by the concomitant administration of CGRP.The decrease in PCr content in the myocardium induced by ET-1 was attenuated by a slight amount of CGRP (100 pmole) significantly (p<
We concluded that CGRP effectively protected the endothelin-induced myocardial ischemia both hemodynamically and metabolically in the isolated beating heats of rats. Less
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