Giuliano R, Ruggiero D A, Morrison S, Ernsberger P, Reis D J
Division of Neurobiology, Cornell University Medical College, New York, New York 10021.
J Neurosci. 1989 Mar;9(3):923-42. doi: 10.1523/JNEUROSCI.09-03-00923.1989.
In anesthetized, paralyzed rats intravenous administration of the acetylcholinesterase inhibitor physostigmine (PHY) (100 micrograms/kg) evoked a dose-related rise in arterial pressure (AP) and heart rate (HR) and an associated increase in sympathetic nerve activity (SNA). The responses to PHY were blocked by electrolytic lesions of, or microinjection of kainic acid into, a specific site in the rostral ventrolateral medulla containing a cluster of neurons immunoreactive for the adrenaline-synthesizing enzyme phenylethanolamine N-methyltransferase and corresponding to the C1 area of the nucleus reticularis rostroventrolateralis (RVL). The C1 area and its surround contain a heretofore unrecognized network of varicose neuronal processes and perikarya labeled immunocytochemically with a monoclonal antibody to the ACh-synthesizing enzyme, choline acetyltransferase (CAT). PHY increased, by over 3-fold, the spontaneous activity of reticulospinal cardiovascular neurons in the C1 area which excite preganglionic sympathetic neurons in the intermediolateral spinal column. The effects of PHY on AP, SNA, and the discharge of reticulospinal neurons were blocked by systemic administration of the muscarinic antagonist scopolamine. Microinjections within the C1 area of the RVL of scopolamine, the M2-selective muscarinic receptor antagonist AF-DX 116, or the high-affinity choline uptake inhibitor hemicholinium-3 blocked the pressor effects of PHY. The nicotinic antagonist hexamethonium and the M1-selective muscarinic receptor antagonist pirenzepine were without effect. We conclude that (1) the increases in AP, HR, and SNA elicited by the systemic administration of PHY result from the augmented action of ACh released from cholinergic terminals within the C1 area of the RVL; (2) the locally released ACh acts through muscarinic receptors of the M2 subtype within the C1 area to produce excitation of intrinsic reticulospinal sympathoexcitatory neurons, thereby increasing the activity of sympathetic preganglionic neurons and consequently elevating AP and HR; and (3) while the specific function of the cholinergic innervation of the C1 area in cardiovascular regulation is unknown, it may contribute to the tonic regulation of AP.
在麻醉、麻痹的大鼠中，静脉注射乙酰胆碱酯酶抑制剂毒扁豆碱（PHY）（100微克/千克）可引起动脉血压（AP）和心率（HR）呈剂量相关的升高以及交感神经活动（SNA）的相应增加。对PHY的反应可被电解损毁或向延髓头端腹外侧特定部位微量注射 kainic 酸所阻断，该部位含有一群对肾上腺素合成酶苯乙醇胺 N -甲基转移酶免疫反应阳性的神经元，对应于延髓头端腹外侧网状核（RVL）的C1区。C1区及其周围包含一个此前未被认识的曲张神经突和胞体网络，用抗乙酰胆碱合成酶胆碱乙酰转移酶（CAT）的单克隆抗体进行免疫细胞化学标记。PHY使C1区中兴奋脊髓中间外侧柱节前交感神经元的网状脊髓心血管神经元的自发活动增加了3倍多。PHY对AP、SNA和网状脊髓神经元放电的影响可被全身给予毒蕈碱拮抗剂东莨菪碱所阻断。在RVL的C1区内微量注射东莨菪碱、M2选择性毒蕈碱受体拮抗剂AF - DX 116或高亲和力胆碱摄取抑制剂半胱氨酸-3可阻断PHY的升压作用。烟碱拮抗剂六甲铵和M1选择性毒蕈碱受体拮抗剂哌仑西平无效。我们得出结论：（1）全身给予PHY引起的AP、HR和SNA增加是由于RVL的C1区内胆碱能终末释放的乙酰胆碱作用增强所致；（2）局部释放的乙酰胆碱通过C1区内M2亚型的毒蕈碱受体起作用，以激发内在的网状脊髓交感兴奋神经元，从而增加交感节前神经元的活动，进而升高AP和HR；（3）虽然C1区胆碱能神经支配在心血管调节中的具体功能尚不清楚，但它可能有助于AP的紧张性调节。
