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[肾上腺素能受体与基因敲除小鼠:1)β肾上腺素能受体基因敲除小鼠]

[Adrenergic receptor and knockout mouse: 1) Beta adrenergic receptor knockout mouse].

作者信息

Mizobe T

机构信息

Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566.

出版信息

Masui. 2000 Dec;49(12):1349-57.

Abstract

Functional analysis of beta 1 and beta 2 adrenergic receptor (AR) subtypes has been made possible by establishing knockout mice (KO) with abolished beta 1 and/or beta 2 AR expression. Neither resting heart rate nor resting blood pressure of beta 1 AR KO, beta 2 AR KO, or beta 1/beta 2 KO differed significantly from those of wild-type mice. The chronotropic response to isoproterenol was significantly attenuated in beta 1 AR KO and beta 1/beta 2 KO, whereas there was no detrimental effect on heart rate in beta 2 AR KO. This suggests that chronotropy is mediated by beta 1 AR. In terms of the vasodilatory response to isoproterenol, there appears to be a graded and additive attenuation of the hypotensive response in beta 1 AR KO, beta 2 AR KO, and beta 1/beta 2 KO. Vascular relaxation is thought to be controlled by both beta 1 AR and beta 2 AR. Tachycardia induced by exercise was significantly attenuated in beta 1 AR KO, and beta 1/beta 2 KO. beta 2 AR KO subjected to treadmill exercise showed significant hypertension, increased oxygen consumption, and ability of long distance running.

摘要

通过建立β1和/或β2肾上腺素能受体(AR)表达缺失的基因敲除小鼠(KO),对β1和β2肾上腺素能受体亚型进行功能分析成为可能。β1 AR基因敲除小鼠、β2 AR基因敲除小鼠或β1/β2基因敲除小鼠的静息心率和静息血压与野生型小鼠相比均无显著差异。β1 AR基因敲除小鼠和β1/β2基因敲除小鼠对异丙肾上腺素的变时反应显著减弱,而β2 AR基因敲除小鼠的心率没有受到不利影响。这表明变时性是由β1肾上腺素能受体介导的。就对异丙肾上腺素的血管舒张反应而言,β1 AR基因敲除小鼠、β2 AR基因敲除小鼠和β1/β2基因敲除小鼠的降压反应似乎存在分级和累加性减弱。血管舒张被认为受β1肾上腺素能受体和β2肾上腺素能受体两者控制。运动诱导的心动过速在β1 AR基因敲除小鼠和β1/β2基因敲除小鼠中显著减弱。进行跑步机运动的β2 AR基因敲除小鼠表现出明显的高血压、耗氧量增加和长跑能力。

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