Role of Angiotensin II Type 1A Receptors in Cardiovascular Reactivity and Neuronal Activation After Aversive Stress in Mice
Role of Angiotensin II Type 1A Receptors in Cardiovascular Reactivity and Neuronal Activation After Aversive Stress in Mice
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DOI：
10.1161/hypertensionaha.109.139741
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发表时间：
2009-12-01
期刊：
影响因子：
8.3
通讯作者：
Mayorov, Dmitry N.
中科院分区：
文献类型：
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作者：
Davern, Pamela J.;Chen, Daian;Mayorov, Dmitry N.
我们确定了小鼠血管紧张素 II 1A 型 (AT(1A)) 受体的遗传缺陷是否会导致神经元反应性改变和心血管对压力的反应性降低。遥测设备用于测量平均动脉压、心率和活动。在应激前，AT(1A)(-/-) (85 +/- 2 mm Hg) 小鼠的静息平均动脉压低于 AT(1A)(+/+) (112 +/- 2 mm Hg) 小鼠；各组之间的心率没有差异。 90 分钟的笼子转换应激使 AT(1A)(+/+) 小鼠血压升高 +24 +/- 2 mmHg，AT(1A)(-/-) 小鼠血压升高 +17 +/- 2 mmHg (P < 0.01)，AT(1A)(+/+) 小鼠心率升高 +203 +/- 9 bpm，AT(1A)(-/-) 小鼠心率升高 +121 +/- 9 bpm （P<0.001）。 AT(1A)(-/-) (3.0 +/- 0.4 U) 的运动激活低于 AT(1A)(+/+) 动物 (6.0 +/- 0.4 U)，但在非活动期间血压和心率的差异仍然存在。与野生型小鼠相比，AT(1A)(-/-) 小鼠的自发压力反射敏感性不受应激的抑制。笼开关应激后，与 AT(1A)(+/+) 小鼠相比，AT(1A)(-/-) 小鼠下丘脑室旁核 (P < 0.001) 和背内侧核 (P = 0.001) 以及延髓头端腹外侧核 (P < 0.001) 的 c-Fos 免疫反应性较低。相反，与 AT(1A)(-/-) 小鼠相比，AT(1A)(-/-) 小鼠的杏仁核内侧核、尾部腹外侧延髓和孤束核中观察到更高的 c-Fos 免疫反应性 (P < 0.001)。杏仁核的较大激活表明 AT(1A) 受体通常会抑制压力引起的焦虑程度，而下丘脑和头端腹外侧延髓的较小激活表明 AT(1A) 受体在对急性厌恶性压力的自主心血管反应以及压力引起的压力感受反射抑制中发挥关键作用。 （高血压。2009；54：1262-1268。）
We determined whether genetic deficiency of angiotensin II Type 1A (AT(1A)) receptors in mice results in altered neuronal responsiveness and reduced cardiovascular reactivity to stress. Telemetry devices were used to measure mean arterial pressure, heart rate, and activity. Before stress, lower resting mean arterial pressure was recorded in AT(1A)(-/-) (85 +/- 2 mm Hg) than in AT(1A)(+/+) (112 +/- 2 mm Hg) mice; heart rate was not different between groups. Cage-switch stress for 90 minutes elevated blood pressure by +24 +/- 2 mmHg in AT(1A)(+/+) and +17 +/- 2 mmHg in AT(1A)(-/-) mice (P < 0.01), and heart rate increased by +203 +/- 9 bpm in AT(1A)(+/+) and +121 +/- 9 bpm in AT(1A)(-/-) mice (P < 0.001). Locomotor activation was less in AT(1A)(-/-) (3.0 +/- 0.4 U) than in AT(1A)(+/+) animals (6.0 +/- 0.4 U), but differences in blood pressure and heart rate persisted during nonactive periods. In contrast to wild-type mice, spontaneous baroreflex sensitivity was not inhibited by stress in AT(1A)(-/-) mice. After cage-switch stress, c-Fos immunoreactivity was less in the paraventricular (P < 0.001) and dorsomedial (P = 0.001) nuclei of the hypothalamus and rostral ventrolateral medulla (P < 0.001) in AT(1A)(-/-) compared with AT(1A)(+/+) mice. Conversely, greater c-Fos immunoreactivity was observed in the medial nucleus of the amygdala, caudal ventrolateral medulla, and nucleus of the solitary tract (P < 0.001) of AT(1A)(-/-) compared with AT(1A)(-/-) mice. Greater activation of the amygdala suggests that AT(1A) receptors normally inhibit the degree of stress-induced anxiety, whereas the lesser activation of the hypothalamus and rostral ventrolateral medulla suggests that AT(1A) receptors play a key role in autonomic cardiovascular reactions to acute aversive stress, as well as for stress-induced inhibition of the baroreflex. (Hypertension. 2009; 54: 1262-1268.)