Moreira Thiago S, Takakura Ana C, Colombari Eduardo, Guyenet Patrice G
Department of Pharmacology, University of Virginia, Charlottesville, VA, 22908, USA.
J Physiol. 2006 Nov 15;577(Pt 1):369-86. doi: 10.1113/jphysiol.2006.115600. Epub 2006 Aug 10.
The present study explores how elevations in brain P(CO(2)) increase the sympathetic nerve discharge (SND). SND, phrenic nerve discharge (PND) and putative sympathoexcitatory vasomotor neurons of the rostral ventrolateral medulla (RVLM) were recorded in anaesthetized sino-aortic denervated and vagotomized rats. Hypercapnia (end-expiratory CO(2) from 5% to 10%) increased SND (97 +/- 6%) and the activity of RVLM neurons (67 +/- 4%). Injection of kynurenic acid (Kyn, ionotropic glutamate receptor antagonist) into RVLM or the retrotrapezoid nucleus (RTN) eliminated or reduced PND, respectively, but did not change the effect of CO(2) on SND. Bilateral injection of Kyn or muscimol into the rostral ventral respiratory group (rVRG-pre-Bötzinger region, also called CVLM) eliminated PND while increasing the stimulatory effect of CO(2) on SND. Muscimol injection into commissural part of the solitary tract nucleus (commNTS) had no effect on PND or SND activation by CO(2). As expected, injection of Kyn into RVLM or muscimol into commNTS virtually blocked the effect of carotid body stimulation on SND in rats with intact carotid sinus nerves. In conclusion, CO(2) increases SND by activating RVLM sympathoexcitatory neurons. The relevant central chemoreceptors are probably located within or close to RVLM and not in the NTS or in the rVRG-pre-Bötzinger/CVLM region. RVLM sympathoexcitatory neurons may be intrinsically pH-sensitive and/or receive excitatory synaptic inputs from RTN chemoreceptors. Activation of the central respiratory network reduces the overall sympathetic response to CO(2), presumably by activating barosensitive CVLM neurons and inhibiting RTN chemoreceptors.
本研究探讨脑内P(CO₂)升高如何增加交感神经放电(SND)。在麻醉的去窦神经和迷走神经切断的大鼠中记录SND、膈神经放电(PND)以及延髓头端腹外侧区(RVLM)假定的交感兴奋血管运动神经元。高碳酸血症(呼气末CO₂从5%升至10%)使SND增加(97±6%)，并使RVLM神经元的活动增加(67±4%)。向RVLM或延髓后外侧核(RTN)注射犬尿氨酸(Kyn，离子型谷氨酸受体拮抗剂)分别消除或降低了PND，但未改变CO₂对SND的作用。向头端腹侧呼吸组(rVRG-前包钦格复合体区域，也称为CVLM)双侧注射Kyn或蝇蕈醇消除了PND，同时增强了CO₂对SND的刺激作用。向孤束核的连合部(commNTS)注射蝇蕈醇对CO₂激活PND或SND没有影响。正如预期的那样，向RVLM注射Kyn或向commNTS注射蝇蕈醇几乎阻断了完整颈动脉窦神经大鼠中颈动脉体刺激对SND的作用。总之，CO₂通过激活RVLM交感兴奋神经元增加SND。相关的中枢化学感受器可能位于RVLM内或其附近，而不在NTS或rVRG-前包钦格复合体/CVLM区域。RVLM交感兴奋神经元可能本身对pH敏感和/或接受来自RTN化学感受器的兴奋性突触输入。中枢呼吸网络的激活可能通过激活压力敏感的CVLM神经元并抑制RTN化学感受器来降低对CO₂的整体交感反应。
