Wang Z Z, Dinger B G, Stensaas L J, Fidone S J
Department of Physiology, University of Utah School of Medicine, Salt Lake City, USA.
Biol Signals. 1995 May-Jun;4(3):109-16. doi: 10.1159/000109430.
Immunocytochemical and histochemical studies of cat and rat carotid bodies have revealed a plexus of nitric oxide synthase (NOS)-positive nerve fibers associated with lobules of chemosensory type I cells as well as with the carotid body vasculature. NOS-positive fibers originate from (1) autonomic neurons located in the carotid body and distributed along the carotid sinus nerve (CNS) and IXth cranial nerve which terminate in the adventitial layer of carotid body blood vessels, and (2) from unipolar sensory neurons of the petrosal (IXth nerve) ganglion. Carotid bodies incubated with the NO precursor, 3H-arginine, yield 3H-citrulline, the detectable coproduct of NO synthesis. Furthermore, electrical stimulation of the CNS or exposure of carotid bodies to hypoxic incubation media elevates 3H-citrulline formation. Millimolar concentrations of L-arginine inhibit chemoreceptor activity evoked by hypoxia, an effect which is reversed by the specific NOS antagonist, L-NG-nitroarginine methylester (L-NAME, 0.1 mM). Electrical stimulation of CNS C fibers elevates cyclic GMP in the carotid body vasculature and lobules of type I cells. Cyclic GMP production is reduced during stimulation in the presence of L-NAME, a finding consistent with the known ability of NO to activate a soluble form of guanylate cyclase. Further studies showed that brief (< 1 min) stimulation of CNS C fibers inhibits basal chemoreceptor discharge in a perfused/superfused in vitro carotid body preparation, whereas prolonged (> 5 min) stimulation is required to inhibit the response to hypoxia. The inhibitory effect is reversed by L-NAME. Our combined anatomical, neuropharmacological and electrophysiological data suggest that NO plays a dual role in mediating CNS inhibition, one via its actions on the organ's vasculature and the other through direct effects on the chemosensory type I cells. The former pathway involves cholinergic/NOS presumptive parasympathetic autonomic neurons, while the latter may be mediated by axon reflex or primary affarent depolarization of chemosensory nerve terminals.
对猫和大鼠颈动脉体的免疫细胞化学和组织化学研究显示，一氧化氮合酶（NOS）阳性神经纤维丛与化学感受性I型细胞小叶以及颈动脉体脉管系统相关。NOS阳性纤维起源于：（1）位于颈动脉体并沿颈动脉窦神经（中枢神经系统）和终止于颈动脉体血管外膜层的第九对脑神经分布的自主神经元；（2）岩神经节（第九对脑神经）的单极感觉神经元。用NO前体3H-精氨酸孵育的颈动脉体产生3H-瓜氨酸，这是NO合成的可检测副产物。此外，中枢神经系统的电刺激或颈动脉体暴露于低氧孵育培养基中会提高3H-瓜氨酸的形成。毫摩尔浓度的L-精氨酸抑制低氧诱发的化学感受器活性，这种作用可被特异性NOS拮抗剂L-硝基精氨酸甲酯（L-NAME，0.1 mM）逆转。中枢神经系统C纤维的电刺激会提高颈动脉体脉管系统和I型细胞小叶中的环磷酸鸟苷（cGMP）水平。在L-NAME存在的情况下，刺激期间cGMP的产生会减少，这一发现与NO激活可溶性鸟苷酸环化酶的已知能力一致。进一步的研究表明，对中枢神经系统C纤维的短暂（<1分钟）刺激会抑制灌注/超灌注体外颈动脉体制备中的基础化学感受器放电，而需要延长（>5分钟）刺激才能抑制对低氧的反应。L-NAME可逆转这种抑制作用。我们综合的解剖学、神经药理学和电生理学数据表明，NO在介导中枢神经系统抑制中起双重作用，一种是通过其对器官脉管系统的作用，另一种是通过对化学感受性I型细胞的直接作用。前一种途径涉及胆碱能/NOS推定的副交感自主神经元，而后一种途径可能由轴突反射或化学感受神经末梢的初级传入去极化介导。
