Cardiovascular, respiratory and autonomic functions in genetically manipulated mice

测定了三种基因敲除小鼠的循环、呼吸和自主神经功能：内皮素-1(ET-1)基因敲除小鼠、内皮素B受体(ETBR)基因敲除小鼠和兰尼定受体3型(RyR-3)基因敲除小鼠。通过AP功率谱的低频成分或心率变异性来评估交感神经活动。杂合子鼠ET-1基因敲除小鼠的特点是动脉压(AP)升高，交感神经过度活动，对低氧和高二氧化碳的呼吸反射受损。因此，内源性ET-1在生理上参与了心肺稳态。在ETBR为正常小鼠的1/8的突变小鼠中，AP升高，交感神经活动和呼吸正常。这一结果与选择性阻断ETBR对正常小鼠的升压反应一致。因此，ETBRs在生理上有助于降低基础AP水平。纯合子RyR-3基因敲除小鼠表现出心率变异性降低，交感神经控制心率受损。综上所述，基因敲除小鼠是一种有价值的研究资源，特别是在哺乳动物综合生理功能的研究中。

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.