Altered baroreflex responses in α7 deficient mice
Altered baroreflex responses in α7 deficient mice
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DOI：
10.1016/s0166-4328(00)00195-9
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发表时间：
2000-08-01
影响因子：
2.7
通讯作者：
De Biasi, M
中科院分区：
文献类型：
--
作者：
Franceschini, D;Orr-Urtreger, A;De Biasi, M
自主神经系统控制和协调多种心血管功能，包括心率、动脉压、血流量和血管舒缩张力。神经烟碱型乙酰胆碱受体 (nAChR) 是神经系统和心血管系统之间的接口，但尚不清楚哪些 nAChR 亚型在体内调节自主神经功能。含有 α7 亚基的烟碱 AChR 是自主神经节的候选亚型。刺激这些 nAChR 可以通过突触前机制增加神经递质释放，并通过突触后机制介导快速突触传递。为了研究 α 7 nAChR 亚基在心脏自主功能中的作用，我们测量了 α 7 缺失小鼠的压力感受反射介导的反应。在这里，我们表明，α 7 缺失小鼠对血管舒张的交感神经反应受损，因为硝普钠输注引发野生型小鼠心率增加 48％，但 α 7 缺失小鼠仅增加 21％（P < 0.001）。突变小鼠对肾上腺素能激动剂产生超敏感性，尽管交感神经末梢释放去甲肾上腺素可以通过 nAChR 刺激的替代机制引起。 α7缺失小鼠中压力反射介导的副交感反应正常。 α7突变小鼠中压力反射介导的心动过速减少表明含有α7的nAChR参与维持血压稳态的自主反射。 α7突变小鼠可以作为由自主神经功能障碍引起的压力反射损伤的模型。 (C) 2000 Elsevier Science B.V. 保留所有权利。
The autonomic nervous system controls and coordinates several cardiovascular functions, including heart rate, arterial pressure, blood flow and vasomotor tone. Neuronal nicotinic acetylcholine receptors (nAChRs) are the interface between the nervous system and the cardiovascular system, but it is not known which nAChR subtypes regulate autonomic function in vivo. Nicotinic AChRs containing the alpha 7 subunit are a candidate subtype in autonomic ganglia. Stimulation of these nAChRs can increase neurotransmitter release via presynaptic mechanisms, as well as mediate fast synaptic transmission via postsynaptic mechanisms. To investigate the role of the alpha 7 nAChR subunit in cardiac autonomic function, we measured baroreflex-mediated responses in alpha 7 null mice. Here we show that the alpha 7 null mice have impaired sympathetic responses to vasodilatation, as sodium nitroprusside infusion triggered a 48% heart rate increase in wild type mice but only a 21% increase in the alpha 7 nulls (P < 0.001). The mutant mice developed supersensitivity to adrenergic agonists, although norepinephrine release from sympathetic nerve terminals could be elicited through mechanisms alternative to nAChR stimulation. Baroreflex-mediated parasympathetic responses were normal in alpha 7 null mice. The decreased baroreflex-mediated tachycardia in alpha 7 mutant mice indicates that alpha 7-containing nAChRs participate in the autonomic reflex that maintains blood pressure homeostasis. The alpha 7 mutant mice may serve as a model of baroreflex impairment arising from autonomic dysfunction. (C) 2000 Elsevier Science B.V. All rights reserved.