Krowicki Z K, Sharkey K A, Serron S C, Nathan N A, Hornby P J
Department of Pharmacology, Louisiana State University Medical Center, New Orleans 70112, USA.
J Comp Neurol. 1997 Jan 6;377(1):49-69. doi: 10.1002/(sici)1096-9861(19970106)377:1<49::aid-cne6>3.0.co;2-j.
Nitric oxide (NO) has received attention as a vagal nonadrenergic-noncholinergic (NANC) mediator of gastrointestinal relaxation. The dorsal vagal complex (DVC) is the primary hindbrain site of vagal control of the gastrointestinal tract, and yet the subnuclear distribution of NO and its physiological effects have not been analyzed in this nucleus. Therefore, this study estimates the relative number of NO synthase (NOS)-containing neurons in subnuclear regions of the DVC, identifies NOS-containing vagal abdominal preganglionic neurons in the dorsal motor nucleus of the vagus, and defines a role of NO in the DVC in control of gastric motor function. The location of NADPH-diaphorase-positive staining (a marker of NOS activity) and NOS immunoreactivity overlap in the DVC. In the dorsal motor nucleus of the vagus there are positively stained cells caudal to the obex and at its most rostral extent, but not at the intermediate level. Intraperitoneal fluorogold combined with NADPH-diaphorase activity labels approximately 5% and 15% of fluorogold-immunoreactive cells in the caudal and rostral dorsal motor nucleus of the vagus, respectively. Thus, a portion of NOS-containing neurons are preganglionic vagal neurons projecting to the abdominal viscera. In the nucleus tractus solitarius, the majority of NADPH-diaphorase-positive cells are within the centralis, medial, and ventral/ventrolateral subnuclei. Fiber/terminal staining is present in the subnucleus centralis, subnucleus gelatinosus, subpostremal zone, and the medial nucleus tractus solitarius. The presence of NOS terminal staining implicates NO in afferent control of gastric function in the DVC (e.g., vago-vagal circuits in subnucleus gelatinosus). To determine a role of NO in the DVC, NO-related agents were microinjected into the DVC in alpha-chloralose-anesthetized rats while recording indices of gastric motor function. L-Arginine, microinjected into the DVC, significantly decreases intragastric pressure (-2.2 +/- 0.4 cm2, N = 12), and this effect is abolished by vagotomy. Microinjection of an NOS inhibitor, NG-nitro-L-arginine methyl ester, increases intragastric pressure (1.9 +/- 0.7 cm2, N = 10), with the greatest effect in the DVC rostral to the obex. Overall, it was concluded that tonic release of NO in the DVC mediates gastric relaxation, at least in anesthetized animals, and NOS-containing preganglionic neurons in the dorsal motor nucleus of the vagus may be "command" NANC neurons which control a variety of gastrointestinal functions.
一氧化氮（NO）作为胃肠道舒张的迷走神经非肾上腺素能-非胆碱能（NANC）介质受到关注。迷走神经背侧复合体（DVC）是迷走神经对胃肠道控制的主要后脑部位，然而该核团中NO的亚核分布及其生理作用尚未得到分析。因此，本研究估计了DVC亚核区域中含一氧化氮合酶（NOS）神经元的相对数量，鉴定了迷走神经背运动核中含NOS的迷走神经腹部节前神经元，并确定了DVC中NO在控制胃运动功能中的作用。DVC中烟酰胺腺嘌呤二核苷酸磷酸黄递酶阳性染色（NOS活性的标志物）和NOS免疫反应性的位置重叠。在迷走神经背运动核中，在闩尾侧及其最前端有阳性染色细胞，但在中间水平没有。腹腔内注射荧光金结合NADPH-黄递酶活性分别标记了迷走神经尾侧和头侧背运动核中约5%和15%的荧光金免疫反应性细胞。因此，一部分含NOS的神经元是投射到腹部内脏的迷走神经节前神经元。在孤束核中，大多数NADPH-黄递酶阳性细胞位于中央、内侧以及腹侧/腹外侧亚核内。纤维/终末染色出现在中央亚核、胶状亚核、最后区以及孤束核内侧核。NOS终末染色的存在表明NO参与DVC中胃功能的传入控制（例如，胶状亚核中的迷走-迷走回路）。为了确定DVC中NO的作用，在α-氯醛糖麻醉的大鼠中，将与NO相关的药物微量注射到DVC中，同时记录胃运动功能指标。向DVC中微量注射L-精氨酸可显著降低胃内压（-2.2±0.4 cm2，N = 12），切断迷走神经后该效应消失。微量注射NOS抑制剂NG-硝基-L-精氨酸甲酯可增加胃内压（1.9±0.7 cm2，N = 10），在闩头侧的DVC中作用最为明显。总体而言，得出的结论是，至少在麻醉动物中，DVC中NO的持续性释放介导胃舒张，迷走神经背运动核中含NOS的节前神经元可能是控制多种胃肠功能的“指令”NANC神经元。
