Alpha2A-adrenergic receptors mediate sympathoinhibitory responses to atrial natriuretic peptide in the mouse anterior hypothalamic nucleus.
Alpha2A-adrenergic receptors mediate sympathoinhibitory responses to atrial natriuretic peptide in the mouse anterior hypothalamic nucleus.
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α2A-肾上腺素能受体介导小鼠下丘脑前核中对心房钠尿肽的交感抑制反应。
DOI：
10.1161/01.hyp.0000056998.83031.22
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Wyss,JMichael
中科院分区：
文献类型：
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作者：
Peng,Ning;Chambless,BrandonD;Oparil,Suzanne;Wyss,JMichael
在大鼠中，下丘脑前核中α2-肾上腺素能受体的激活会抑制交感神经系统的活动。此外，心房钠尿肽的局部释放抑制该核中去甲肾上腺素的释放，阻断α2-肾上腺素能受体的局部激活，从而导致自发性高血压大鼠的氯化钠敏感性高血压。为了进一步测试该机制的特异性，将α2-肾上腺素受体激动剂或心房钠尿肽显微注射到有意识的C57BL/6小鼠的下丘脑前核中，其中α2-肾上腺素受体通过单点突变在功能上被删除（每组n = 10）。在对照小鼠中，显微注射可乐定或胍那苯（10−3 至 10−7mol/L）会导致平均动脉压迅速下降，并持续几分钟。在基因敲除小鼠中，注射任何剂量的任一激动剂都没有反应。显微注射心房钠尿肽（10−6 至 10−7mol/L）导致对照小鼠平均动脉压迅速升高（分别为 8.2±1.3 和 6.55±1.2 mm Hg），这与之前在 Wistar-Kyoto 大鼠中观察到的反应相似。相比之下，显微注射并没有显着改变基因敲除小鼠的平均动脉压。这些实验表明，在小鼠（也可能在大鼠）的下丘脑前核中，α2A-肾上腺素能受体介导对α2-肾上腺素能受体激动剂的交感神经抑制反应和心房钠尿肽的作用。
In the rat, activation of α2-adrenergic receptors in the anterior hypothalamic nucleus inhibits sympathetic nervous system activity. Furthermore, local release of atrial natriuretic peptide inhibits norepinephrine release in this nucleus, blocking local activation of α2-adrenergic receptors, and thereby contributes to NaCl-sensitive hypertension in spontaneously hypertensive rats. To further test the specificity of this mechanism, either α2-adrenergic receptor agonists or atrial natriuretic peptide was microinjected into anterior hypothalamic nucleus of conscious C57BL/6 mice in which the α2-adrenergic receptor was functionally deleted by a single point mutation (n=10 per group). In control mice, microinjection of either clonidine or guanabenz (10−3to 10−7mol/L) caused a rapid fall in mean arterial pressure that lasted for several minutes. In the knockout mice there was no response to the injection of either dose of either agonist. Microinjection of atrial natriuretic peptide (10−6to 10−7mol/L) caused a rapid increase in mean arterial pressure (8.2±1.3 and 6.55±1.2 mm Hg, respectively) in the control mice that was similar to the responses previously observed in Wistar-Kyoto rats. In contrast, the microinjections did not significantly alter mean arterial pressure in the knockout mice. These experiments demonstrate that in the anterior hypothalamic nucleus of the mouse (and probably in the rat) α2A-adrenergic receptors mediate both sympathoinhibitory responses to α2-adrenergic receptor agonists and the action of atrial natriuretic peptide.