| Project/Area Number |
07457576
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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 physiology
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| Research Institution | University of Tokyo |
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Principal Investigator |
KUMADA Mamoru University of Tokyo, Faculty of Medicine, Department of Physiology, Professor, 医学部, 教授 (00110487)
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| Co-Investigator(Kenkyū-buntansha) |
KUWAKI Tomoyuki University of Tokyo, Faculty of Medicine, Department of Physioogy, Instructor, 医学部, 助手 (80205260)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | knockout mouse / endothelin-1 / endothelin B receptor / ryanodine type 3 receptor / power spectral analysis / arterial pressure / respiratory reflex / sympathetic nerve activity / 血小板活性化因子受容体 / 交感神経 / アナフィラキシ-ショック / 遺伝子操作マウス / 呼吸運動 / 自律神経 / 血管運動神経 / 心臓交感神経 |
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| Research Abstract |
Circulatory, respiratory, and autonomic functions were measured in three types of knockout mice : endothelin-1 (ET-1) knockout mouse, endothelin B receptor (ETBR) knockout mouse, and ryanodine receptor type 3 (RyR-3) knockout mouse. Sympathetic nerve activity was assessed by the low frequency component of the power spectrum of AP or heart rate (HR) variability. Heterozygouse ET-1 knockout mice were characterized by increased arterial pressure (AP) with sympathetic overactivity and impaired respiratory reflex to hypoxia and hypercapnia. Endogenous ET-1 thus physiologically participates in the cardiorespiratory homeostasis. In mutant mice in which ETBR was 1/8 of normal mice, AP was elevated with normal sympathetic activity and respiration. The result is consistent with a pressor response to selective blockade of ETBR in normal mice. Thus, ETBRs contribute physiologically to diminish basal level of AP.Homozygous RyR-3 knockout mice showed diminished HR variability with impaired HR control by the sympathetic nerve. In conclusion, knockout mice are a valuable research resource especially in the study of integrative physiological functions of mammals.
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