1996 Fiscal Year Final Research Report Summary
Cardiovascular, respiratory and autonomic functions in genetically manipulated mice
| 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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| Keywords | knockout mouse / endothelin-1 / endothelin B receptor / ryanodine type 3 receptor / power spectral analysis / arterial pressure / respiratory reflex / sympathetic nerve activity |
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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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[Publications] Ju, K.H., Kuwaki, T., Cao, W.H., Ling, G.Y., Onodera, Y., Kurihara, H., Kurihara, H., Yazaki, Y., and Kumada, M.: "Power spectral analysis of arterial blood pressure in mice : comparison between normal and endothelin-1 gene knocked out mice" Proc.IEEE-CMBEC. 119-120 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Maemura, K., Kurihara, H., Kurihara, Y., Kuwaki, T., Kumada, M.& Yazaki, Y.: "Gene expression of endothelin isoforms and receptors in endotheline-1 knockout mice" J.Cardiovasc.Pharmacol.26. S17-S21 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Ju, K-H., Kuwaki, T., Cao, W-H., Ling, G-Y., Onodera, Kurihara, Y., Kurihara, H., Yazaki, Y.Kumada, M.: "Power spectral analysis of arterial blood pressure in mice : comparisonbetween normaland endothelin-1 gene knocked out mice" Proc.IEEE & M., EMBC & CMBE. 119-120 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Kuwaki, T., Cao, W-H., Kurihara, Y., Kurihara, H., Ling, G-Y., Onodera, M., Ju, K-H., Yazaki Y.& Kumada, M.: "Impaired ventilatory responses to hypoxia and hypercapnia in mutant mice deficient in endothelin-1" Am.J.Physiol.270. R1279-R1286 (1996)
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「研究成果報告書概要(欧文)」より
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