| Project/Area Number |
08457024
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
GOTO Katsutoshi University of Tsukuba, Institute of Basic Medical Sciences, Professor, 基礎医学系, 教授 (30012660)
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| Co-Investigator(Kenkyū-buntansha) |
SAKURAI Takeshi University of Tsukuba, Institute of Basic Medical Sciences, Assistant Professor, 基礎医学系, 講師 (60251055)
KASUYA Yoshitoshi University of Tsukuba, Institute of Basic Medical Sciences, Assistant Professor, 基礎医学系, 講師 (70221877)
ISHIKAWA Tomohisa University of Tsukuba, Institute of Basic Medical Sciences, Assistant Professor (10201914)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1997: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1996: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | regional blood flow / hindlimb / askeletal muscle / sensory nerve / CGRP / CO2 / capsaicin / カルシトニン遺伝子関連ペプチド / 二酸化炭素 / 血流 / 血管弛緩 / EDHF / ラット |
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| Research Abstract |
The mechanism of neurogenic regulation of skeletal muscle circulation was studied in the hindlimb of anesthetized rats in vivo. Electrical stimulation of sciatic nerve (10 Hz for 1 min) caused a sustained increase in regional blood flow (RBF). This increase in RBF was shown to be a secondary response brought about by the muscle contraction. Further, it was also demonstrated that this response was produced via excitation of capsaicin-sensitive sensory nerves. Serum Levels of calcitonin gene-related peptide (CGRP) in iliac venous effluent significantly increased during the hyperaemic response to skeletal muscle contraction. A bolus intra-arterial. injection of CGRP induced a long-lasting increase in RBF.CGRP(8-37), a specific CGRP_1 receptor antagonist, significantly suppressed the hyperaemic responses induced by either CGRP or skeletal muscle contraction, especially the sustained phase of the response which was almost abolished by this antagonist. During muscle contraction-induced haperaemia, partial pressure of CO_2 in the venous effluent from the hindlimb significantly increased with no change in pH and partial pressure of O_2. An intra-arterial injection of NaHCO_3 (titrated to pH 7.2 with HCl) caused a sustained increase in REF and, simulataneously, increases in CGRP level and partial pressure of CO_2 in the blood. These results suggest that CO_2 liberated from excercising akeletal muscle activates capsaicin-sensitive perivascular sensory nerves locally, which causes the release of CGRP from their peripheral ending and causes vascular relaxation, thereby resulting in local hyperaemia.
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