Cardiovascular, respiratory and autonomic functions in genetically manipulated mice

基因改造小鼠的心血管、呼吸和自主功能

• 批准号: 07457576
• 负责人: KUMADA Mamoru
• 金额: $ 0.51万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457576/
• 关键词: 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

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.

在三种类型的敲除小鼠中测量循环、呼吸和自主神经功能：内皮素-1 （ET-1）敲除小鼠、内皮素B受体（ETBR）敲除小鼠和赖亚诺定受体3型（RyR-3）敲除小鼠。交感神经活动通过AP功率谱的低频分量或心率变异性来评估。杂合子ET-1敲除小鼠的特征是动脉压升高，交感神经过度活跃，对缺氧和高碳血症的呼吸反射受损。因此，内源性ET-1在生理上参与了心肺稳态。在ETBR为正常小鼠1/8的突变小鼠中，AP升高，交感神经活动和呼吸正常。结果与正常小鼠选择性阻断ETBR的压力反应一致。因此，etbr在生理上有助于降低ap的基础水平。纯合的RyR-3基因敲除小鼠的HR变异性降低，交感神经对HR的控制受损。总之，基因敲除小鼠是研究哺乳动物综合生理功能的宝贵资源。

项目成果

Ono, A., Kuwaki, T., Kumada, M.& Fujita, Y.: "Differential modulation of baroreflex by salt loading in normotensive and spontaneously hypertensive rats" Hypertension. (In press). (1997)

小野，A.，桑木，T.，熊田，M.

YUKIKO KURIHARA: "IMPAIRED DEVELOPMENT OF THE THYROID AND THYMUS IN ENDOTHELIN-1 KNOCKOUT M" JOURNAL OF CARDIOVASCULAR PHARMACOLOGY. 26(SUPPL3). S13-S16 (1995)

Yukiko Kurihara：“内皮素-1 敲除 M 导致甲状腺和胸腺发育受损”心血管药理学杂志。

Tezuka, T., Sugishita, C., Kuwaki, T., Higurashi, M.& Kumada, M.: "Effects of compression stockings on blood pressure and its orthostatic change in female subjects" Pathophysiology. (In press). (1997)

手冢 T.、杉下 C.、桑木 T.、日暮 M.

WEI CAO: "ABNORMAL CENTRAL RESPIRATORY MECHANISM IN ENDOTHELIN-1 DEFICIENT MECE:A STUDY IN MEDULLA-SPINAL CORD PREPARATION" NEUROSCIENCE RESEARCH. SUPPL.20. S72-S72 (1996)

曹伟：“内皮素-1 缺乏 MECE 中的中枢呼吸机制异常：延髓-脊髓准备的研究”神经科学研究。

TOMOYUKI KUWAKI: "IMPAIRED VENTILATORY RESPONSES TO HYPOXIA AND HYPERCAPNIA IN MUTANT MICE DEFICIENT IN ENDOTHELIN-1" AMERICAN JOURNAL OF PHYSIOLOGY. (in press).

Tomoyuki 桑木：“内皮素-1 缺陷突变小鼠对缺氧和高碳酸血症的通气反应受损”美国生理学杂志。