Wang Z Z, Stensaas L J, Dinger B G, Fidone S J
Department of Physiology, University of Utah School of Medicine, Salt Lake City 84108, USA.
Neuroscience. 1995 Mar;65(1):217-29. doi: 10.1016/0306-4522(94)00437-a.
Numerous studies have demonstrated that carotid sinus nerve fibers mediate a so-called "efferent" inhibition of carotid body chemoreceptors. However, the mechanism(s) underlying this phenomenon are not understood. Recently, it has been shown that an extensive plexus of nitric oxide synthase-containing carotid sinus nerve fibers innervate the carotid body, and that many fine, beaded fibers can be seen in close proximity to small blood vessels as well as lobules of parenchymal cells. The present study examined the effects of centrifugal neural activity in the carotid sinus nerve on the accumulation of [3H]citrulline synthesized from [3H]arginine in the cat carotid body, and the possible involvement of nitric oxide in mediating "efferent" chemoreceptor inhibition. Electrical stimulation of carotid sinus nerve C-fibers evoked an increase in [3H]citrulline accumulation in the carotid body, which was Ca(2+)-dependent and blocked by L-NG-nitroarginine methylester (0.1 mM), an inhibitor of nitric oxide synthase. Using a vascularly perfused in vitro carotid body preparation, chemoreceptor activity was recorded from thin nerve filaments split-off from the main trunk of the carotid sinus nerve. Electrical stimulation of the main nerve trunk at C-fiber intensities inhibited steady-state chemoreceptor discharge, and this effect was blocked by L-NG-nitroarginine methylester. However, when the organ preparation was switched to the superfuse-only mode, carotid sinus nerve stimulation failed to alter the steady-state discharge, but under these conditions, prolonged nerve stimulation (> 5 min) did attenuate the chemoreceptor response to hypoxia, an effect which was likewise blocked by L-NG-nitroarginine methylester. The present data, together with previous anatomical findings that nitric oxide synthase immunoreactivity is present in both sensory and autonomic ganglion cells innervating the carotid body, suggest that two neural mechanisms may be involved in the inhibitory neural regulation of carotid chemoreceptors. One mechanism appears to involve nitric oxide release from intralobular sensory C-fibers, which lie in close proximity to the chemoreceptor type I cells. The other mechanism involves release of nitric oxide from perivascular terminals of autonomic microganglia neurons, which control carotid body blood flow.
大量研究表明，颈动脉窦神经纤维介导对颈动脉体化学感受器的所谓“传出性”抑制。然而，这一现象背后的机制尚不清楚。最近的研究显示，含有一氧化氮合酶的颈动脉窦神经纤维形成广泛的神经丛支配颈动脉体，并且可以看到许多细小的、串珠状纤维紧邻小血管以及实质细胞小叶。本研究检测了颈动脉窦神经中离心神经活动对猫颈动脉体中由[3H]精氨酸合成的[3H]瓜氨酸积累的影响，以及一氧化氮在介导“传出性”化学感受器抑制中的可能作用。电刺激颈动脉窦神经C纤维可引起颈动脉体中[3H]瓜氨酸积累增加，这一过程依赖于Ca(2+)，并被一氧化氮合酶抑制剂L-NG-硝基精氨酸甲酯（0.1 mM）所阻断。使用体外血管灌注的颈动脉体制备，从颈动脉窦神经主干分离出的细神经丝记录化学感受器活动。以C纤维强度电刺激主神经干可抑制稳态化学感受器放电，且这一效应被L-NG-硝基精氨酸甲酯所阻断。然而，当器官制备切换至仅灌注模式时，颈动脉窦神经刺激未能改变稳态放电，但在这些条件下，长时间神经刺激（> 5分钟）确实会减弱化学感受器对缺氧的反应，这一效应同样被L-NG-硝基精氨酸甲酯所阻断。目前的数据，连同先前的解剖学发现，即支配颈动脉体的感觉和自主神经节细胞中均存在一氧化氮合酶免疫反应性，表明可能有两种神经机制参与颈动脉化学感受器的抑制性神经调节。一种机制似乎涉及小叶内感觉C纤维释放一氧化氮，这些C纤维紧邻I型化学感受器细胞。另一种机制涉及自主微神经节神经元血管周围终末释放一氧化氮，这些神经元控制颈动脉体血流。
