Mechanisms of altered vagal control in heart failure: influence of muscarinic receptors and acetylcholinesterase activity
Mechanisms of altered vagal control in heart failure: influence of muscarinic receptors and acetylcholinesterase activity
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DOI：
10.1152/ajpheart.01051.2002
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发表时间：
2003-10-01
影响因子：
4.8
通讯作者：
Ernsberger, P
中科院分区：
文献类型：
--
作者：
Dunlap, ME;Bibevski, S;Ernsberger, P
心脏的副交感神经控制在心力衰竭（HF）中减弱。我们研究了快速起搏引起的心衰犬迷走神经控制改变的可能机制和部位。毒蕈碱阻滞使对照组R-R间期缩短308 ms，但HF组仅缩短32 ms，表明静息迷走神经张力水平较低。在对照组中，硫酸阿托品的迷走剂量使R-R间期延长109 ms，使R-R间期的标准差增加66 ms，但在HF组中分别仅增加46 ms和16 ms。HF组迷走神经电刺激引起的心动过缓也减弱。相反，氨甲胆碱和新斯的明间接激活毒蕈碱受体会引起HF中R-R间期反应过度。为了研究可能的机制，我们测量了心脏不同区域的毒蕈碱受体密度（B-max）和乙酰胆碱酯酶活性。在窦房结中，HF患者的B-max增加（对照组的230 +/- 75%），乙酰胆碱酯酶降低（对照组的80 +/- 6%）。我们的结论是，毒蕈碱受体上调和乙酰胆碱酯酶减少，在窦房结HF。因此，HF中迷走神经控制的减少最有可能是由于突触前功能（神经节）的变化，因为突触后机制增强了HF中迷走神经的控制。
Parasympathetic control of the heart is attenuated in heart failure (HF). We investigated possible mechanisms and sites of altered vagal control in dogs with HF induced by rapid pacing. Muscarinic blockade reduced the R-R interval by 308 ms in controls but only by 32 ms in HF, indicating low levels of resting vagal tone. Vagomimetic doses of atropine sulfate prolonged the R-R interval by 109 ms in controls and increased standard deviation of the R-R interval by 66 ms but only by 46 and 16 ms, respectively, in HF. Bradycardia elicited by electrical stimulation of the vagus nerve was also attenuated in the HF group. Conversely, muscarinic receptor activation by bethanechol, and indirectly by neostigmine, elicited exaggerated R-R interval responses in HF. To investigate possible mechanisms, we measured muscarinic receptor density (B-max) and acetylcholinesterase activity in different areas of the heart. In sinoatrial nodes, B-max was increased (230 +/- 75% of control) and acetylcholinesterase decreased ( 80 +/- 6% of control) in HF. We conclude that muscarinic receptors are upregulated and acetylcholinesterase is reduced in the sinus node in HF. Therefore, reduced vagal control in HF is most likely due to changes of presynaptic function ( ganglionic), because postsynaptic mechanisms augment vagal control in HF.