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Dbh基因敲除小鼠血压过低,昼夜节律改变,对节食和应激的反应异常。

Dbh(-/-) mice are hypotensive, have altered circadian rhythms, and have abnormal responses to dieting and stress.

作者信息

Swoap Steven J, Weinshenker David, Palmiter Richard D, Garber Graham

机构信息

Department of Biology, Williams College, Williamstown, MA 01267, USA.

出版信息

Am J Physiol Regul Integr Comp Physiol. 2004 Jan;286(1):R108-13. doi: 10.1152/ajpregu.00405.2003. Epub 2003 Sep 11.

Abstract

We used mice deficient in dopamine beta-hydroxylase [Dbh(-/-)] and their littermate controls [Dbh(+/-)] to examine the role of epinephrine (Epi) and norepinephrine (NE) in the maintenance of cardiovascular parameters during 7 days of caloric restriction and acute exposure to environmental stress. Cardiovascular parameters of the mice were monitored using blood pressure radiotelemeters at an ambient temperature of 29 degrees C. Under normal conditions, Dbh(-/-) mice had a low heart rate, were severely hypotensive, and displayed an attenuated circadian blood pressure rhythm. Upon 50% caloric restriction, Dbh(+/-) mice exhibited decreases in heart rate and mean blood pressure. However, the blood pressures of Dbh(-/-) mice did not fall significantly in response to caloric restriction, and the bradycardia associated with caloric restriction was attenuated in these mice. In response to an open-field test, the blood pressure and heart rate of Dbh(+/-) mice increased substantially and rapidly, whereas Dbh(-/-) mice had blunted changes in blood pressures and no change in heart rate. These data suggest a primary role of Epi and NE in mediating the hypotension induced by dieting. Furthermore, Epi and NE play a smaller, but still significant, role in the bradycardia induced by caloric restriction. In contrast, Epi and NE are required for the tachycardia in an open field but are not required for the increase in blood pressure.

摘要

我们使用多巴胺β-羟化酶缺陷型小鼠[Dbh(-/-)]及其同窝对照小鼠[Dbh(+/-)],来研究肾上腺素(Epi)和去甲肾上腺素(NE)在热量限制7天及急性暴露于环境应激期间维持心血管参数方面的作用。在29摄氏度的环境温度下,使用血压无线电遥测仪监测小鼠的心血管参数。在正常条件下,Dbh(-/-)小鼠心率较低,严重低血压,且昼夜血压节律减弱。在50%热量限制时,Dbh(+/-)小鼠心率和平均血压下降。然而,Dbh(-/-)小鼠的血压对热量限制没有显著下降,且这些小鼠中与热量限制相关的心动过缓有所减轻。在旷场试验中,Dbh(+/-)小鼠的血压和心率大幅快速升高,而Dbh(-/-)小鼠血压变化不明显且心率无变化。这些数据表明Epi和NE在介导节食引起的低血压中起主要作用。此外,Epi和NE在热量限制引起的心动过缓中起较小但仍显著的作用。相比之下,Epi和NE是旷场试验中心动过速所必需的,但不是血压升高所必需的。

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