Sivarao Digavalli V, Mashimo Hiroshi, Goyal Raj K
Department of Veterans Affairs Medical Center, Center for Swallowing and Motility Disorders, West Roxbury, Massachusetts 02132, USA.
Gastroenterology. 2008 Oct;135(4):1258-66. doi: 10.1053/j.gastro.2008.06.039. Epub 2008 Jun 20.
BACKGROUND & AIMS: Nitrergic nerves and interstitial cells of Cajal (ICC) have been implicated in the regulation of pyloric motility. The purpose of these studies was to define their roles in pyloric function in vivo.
Pyloric sphincter manometry was performed in wild-type controls, neuronal nitric oxide synthase-deficient (nNOS(-/-)) mice, and ICC-deficient W/W(v) mice, and the effect of deafferented cervical vagal stimulation was examined.
Mice showed a distinct approximately 0.6-mm-wide zone of high pressure at the antroduodenal junction, representing the pyloric sphincter. In wild-type controls, the pylorus exhibited tonic active pressure of 12.4 +/- 1.6 mm Hg with superimposed phasic contractions. The motility indices, minute motility index, and total myogenic activity were reduced by vagal stimulation, and the reduction was antagonized by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). In nNOS(-/-) mice, pyloric basal tone, minute motility index, and total myogenic activity were not significantly different from those in controls, but vagal stimulation paradoxically increased pyloric motility. In contrast, the W/W(v) mice had significantly reduced resting pyloric pressure that was suppressed by vagal stimulation in an L-NAME-sensitive manner. The stomachs of fasted nNOS(-/-) mice showed solid food residue and bezoar formation, while W/W(v) mice showed bile reflux.
In nNOS(-/-) mice, loss of nitrergic pyloric inhibition leads to gastric stasis and bezoars. In contrast, basal pyloric hypotension with normal nitrergic inhibition predisposes W/W(v) mice to duodenogastric bile reflux.
含氮能神经和 Cajal 间质细胞（ICC）参与幽门运动的调节。这些研究的目的是确定它们在体内幽门功能中的作用。
在野生型对照、神经元型一氧化氮合酶缺陷（nNOS(-/-)）小鼠和 ICC 缺陷的 W/W(v)小鼠中进行幽门括约肌测压，并检测去传入神经的颈迷走神经刺激的效果。
小鼠在胃十二指肠交界处显示出一个明显的约 0.6 毫米宽的高压区，代表幽门括约肌。在野生型对照中，幽门表现出 12.4±1.6 毫米汞柱的紧张性主动压力，并伴有叠加的节律性收缩。运动指数、每分钟运动指数和总肌源性活动在迷走神经刺激下降低，且这种降低被一氧化氮合酶抑制剂 N(G)-硝基-L-精氨酸甲酯（L-NAME）拮抗。在 nNOS(-/-)小鼠中，幽门基础张力、每分钟运动指数和总肌源性活动与对照组相比无显著差异，但迷走神经刺激反而增加了幽门运动。相比之下，W/W(v)小鼠的静息幽门压力显著降低，且以 L-NAME 敏感的方式被迷走神经刺激所抑制。禁食的 nNOS(-/-)小鼠胃内有固体食物残渣和胃石形成，而 W/W(v)小鼠则出现胆汁反流。
在 nNOS(-/-)小鼠中，含氮能的幽门抑制丧失导致胃潴留和胃石形成。相比之下，具有正常含氮能抑制的基础幽门低血压使 W/W(v)小鼠易发生十二指肠-胃胆汁反流。
