Expression of Angiotensin Type 1A Receptors in C1 Neurons Restores the Sympathoexcitation to Angiotensin in the Rostral Ventrolateral Medulla of Angiotensin Type 1A Knockout Mice
Expression of Angiotensin Type 1A Receptors in C1 Neurons Restores the Sympathoexcitation to Angiotensin in the Rostral Ventrolateral Medulla of Angiotensin Type 1A Knockout Mice
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DOI：
10.1161/hypertensionaha.110.151704
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发表时间：
2010-07-01
期刊：
影响因子：
8.3
通讯作者：
Allen, Andrew M.
中科院分区：
文献类型：
--
作者：
Chen, Daian;Bassi, Jaspreet K.;Allen, Andrew M.
在成年小鼠中，我们确定 C1 神经元中血管紧张素 II (Ang II) 1A 型受体 (AT(1A)Rs) 的表达是否介导 Ang II 对头侧延髓腹外侧 (RVLM) 的兴奋。在麻醉、人工通气的野生型 (n = 15) 和 AT(1A)R 敲除小鼠 (AT(1A)(-/-)；n = 9) 小鼠中测量血压、心率和交感神经活动。将 Ang II（50 nL，0.1 至 1.0 mmol/L）显微注射到 RVLM 中，在野生型小鼠中诱导剂量相关的交感神经介导的升压反应（最大 17 +/- 2 mm Hg）。这些显微注射对 AT(1A)(-/-) 小鼠没有影响。内源性 AT(1)R 发生在 RVLM 中的儿茶酚胺能 C1 神经元上。我们通过双侧显微注射复制缺陷型慢病毒，诱导 AT(1A)(-/-) 小鼠 C1 神经元中 AT(1A)R 或绿色荧光蛋白表达，转基因表达受 phox2 转录因子结合启动子 (PRSx8) 控制（Lv-PRSx8-AT(1A)，n = 10，和 Lv-PRSx8-GFP，n = 5）。在相当比例的 RVLM C1 神经元中观察到转基因表达。在注射 Lv-PRSx8-AT1A 的麻醉小鼠中，单侧 RVLM 显微注射 Ang II（50 nL，1 mmol/L）会增加血压（17 +/- 4 mm Hg）和交感神经活动（155 +/- 32%）。 Lv-PRSx8-GFP 显微注射小鼠对 Ang II 没有反应。这些结果表明，成年小鼠中 Ang II 介导的 RVLM 神经元兴奋依赖于 AT(1A)R，而 1B 型或 2 型受体的影响很小或没有。 AT(1A)R 主要在 C1 儿茶酚胺神经元中表达，可恢复 AT(1A)(-/-) 小鼠对 Ang II 的反应，并表明这些神经元在小鼠中具有交感兴奋性。 （高血压。2010；56：143-150。）
In adult mice we determined whether expression of angiotensin II (Ang II) type 1A receptors (AT(1A)Rs) in C1 neurons mediates the excitation of the rostral ventrolateral medulla (RVLM) by Ang II. Blood pressure, heart rate, and sympathetic nerve activity were measured in anesthetized, artificially ventilated wild-type (n = 15) and AT(1A)R knockout (AT(1A)(-/-); n = 9) mice. Microinjection of Ang II (50 nL of 0.1 to 1.0 mmol/L) into the RVLM induced a dose-related, sympathetically mediated pressor response (maximum of 17 +/- 2 mm Hg) in wild-type mice. These microinjections had no effect in AT(1A)(-/-) mice. Endogenous AT(1)Rs occur on catecholaminergic C1 neurons in the RVLM. We induced AT(1A)R or green fluorescent protein expression in C1 neurons of AT(1A)(-/-) mice through bilateral microinjection of replication-deficient lentiviruses, with transgene expression under the control of a phox2 transcription factor binding promoter (PRSx8) (Lv-PRSx8-AT(1A), n = 10, and Lv-PRSx8-GFP, n = 5). Transgene expression was observed in a significant proportion of RVLM C1 neurons. In anesthetized Lv-PRSx8-AT1A injected mice, unilateral RVLM microinjection of Ang II (50 nL of 1 mmol/L) increased blood pressure (17 +/- 4 mm Hg) and sympathetic nerve activity (155 +/- 32%). No response to Ang II occurred in Lv-PRSx8-GFP microinjected mice. These results show that Ang II-mediated excitation of RVLM neurons in adult mice depends on the AT(1A)R with little or no effect of type 1B or 2 receptors. Expression of the AT(1A)R predominantly in C1 catecholamine neurons restores the response to Ang II in the AT(1A)(-/-) mouse and demonstrates that these neurons are sympathoexcitatory in the mouse. (Hypertension. 2010; 56: 143-150.)