Bealer J F, Natuzzi E S, Flake A W, Adzick N S, Harrison M R
Department of Surgery, University of California, San Francisco 94143-0570.
J Pediatr Surg. 1994 Aug;29(8):1025-9. doi: 10.1016/0022-3468(94)90272-0.
Hirschsprung's disease results in bowel obstruction because of a failure of smooth muscle relaxation in both the aganglionic segment of bowel and the internal anal sphincter (IAS). Nonadrenergic noncholinergic (NANC) nerves, which use nitric oxide (NO) as their chemical messenger, are responsible for relaxing smooth muscle in normal bowel and the IAS. Previous work indicates that the cause of the aganglionic colon's inability to relax may be a lack of NANC nerves. To test this hypothesis, the authors compared the effect of an exogenous source of NO, S-nitroso-N-acetylpenicillamine (SNAP), on the isometric tension of smooth muscle strips taken from the ganglionic colon, aganglionic colon, and IAS of patients with Hirschsprung's disease. Exposure of ganglionic and aganglionic colon specimens to SNAP (10(-3) to 10(-5) mol/L) resulted in up to 70% reduction of resting tension. This relaxation occurred in a dose-dependent fashion and could be promptly reversed by the addition of the NO antagonist methylene blue. However, SNAP had no demonstrable effect on the smooth muscle strips taken from the IAS of patients with Hirschsprung's disease. This finding suggests that, in the aganglionic colon, a deficiency of NANC nerves contributes to the development of bowel obstruction. However, the failure of the IAS to relax in Hirschsprung's disease appears to be unrelated to NO and the NANC nervous system.
先天性巨结肠症会导致肠梗阻，这是由于肠道无神经节段和肛门内括约肌（IAS）的平滑肌无法松弛所致。以一氧化氮（NO）作为化学信使的非肾上腺素能非胆碱能（NANC）神经，负责使正常肠道和IAS的平滑肌松弛。先前的研究表明，无神经节结肠无法松弛的原因可能是缺乏NANC神经。为了验证这一假设，作者比较了外源性NO供体S-亚硝基-N-乙酰青霉胺（SNAP）对取自先天性巨结肠症患者的神经节结肠、无神经节结肠和IAS的平滑肌条等长张力的影响。将神经节和无神经节结肠标本暴露于SNAP（10⁻³至10⁻⁵mol/L）可使静息张力降低多达70%。这种松弛呈剂量依赖性，并且加入NO拮抗剂亚甲蓝后可迅速逆转。然而，SNAP对取自先天性巨结肠症患者IAS的平滑肌条没有明显影响。这一发现表明，在无神经节结肠中，NANC神经的缺乏导致了肠梗阻的发生。然而，先天性巨结肠症中IAS无法松弛似乎与NO和NANC神经系统无关。
