Yildiz Firuzan, Tugay Melih, Utkan Tijen, Yazir Yusufhan
Department of Pharmacology, Kocaeli Medical School, Kocaeli, Turkey.
J Pediatr Surg. 2007 Apr;42(4):647-52. doi: 10.1016/j.jpedsurg.2006.12.019.
An association between chronic renal failure (CRF) and gastroesophageal reflux (GER) is well known. The aim of this study was to pharmacologically characterize and investigate the possible contribution of smooth muscle reactivity pathways involving GER on the CRF rat model.
Chronic renal failure was created in Sprague-Dawley rats by 5 of 6 nephrectomy. The rats were divided into 2 groups: the CRF-induced group (CRF group) and the sham-operated group (control group). Esophageal smooth muscle strips were studied in vitro for their contractile (KCl, carbachol) and relaxant (isoproterenol, serotonin, and papaverine) response to receptor activation in the organ chambers set up. Subsequently, the in vitro lower esophageal sphincter (LES) smooth muscle study was generated by KCl, carbachol, isoproterenol, nicotine, sodium nitroprusside (SNP), and papaverine.
Compared with controls, esophageal strips taken from CRF-induced rats associated with decreased smooth muscle responses to carbachol, serotonin, and increased response to KCl. Isoproterenol- and papaverine-induced relaxant responses were not affected. Contractility of the isolated LES strips were significantly increased to KCl and carbachol in the CRF group compared with the control group. Similar relaxant responses were obtained in LES strips stimulated by isoproterenol, SNP, and papaverine in the CRF and control group. Nicotine-induced relaxant responses were decreased in the CRF group compared with the control group.
Our study revealed alterations of receptor-dependent esophageal and LES smooth muscle reactivity in the CRF-induced rats. Impaired foregut smooth muscle reactivity may contribute to the development of GER-related functional abnormalities in patients with CRF.
慢性肾衰竭（CRF）与胃食管反流（GER）之间的关联已广为人知。本研究的目的是从药理学角度对涉及GER的平滑肌反应途径进行表征，并研究其在CRF大鼠模型中的可能作用。
通过六肾切除五肾的方法在Sprague-Dawley大鼠中建立慢性肾衰竭模型。将大鼠分为两组：CRF诱导组（CRF组）和假手术组（对照组）。在体外研究食管平滑肌条对器官浴槽中受体激活的收缩反应（氯化钾、卡巴胆碱）和舒张反应（异丙肾上腺素、5-羟色胺和罂粟碱）。随后，通过氯化钾、卡巴胆碱、异丙肾上腺素、尼古丁、硝普钠（SNP）和罂粟碱对体外下食管括约肌（LES）平滑肌进行研究。
与对照组相比，取自CRF诱导大鼠的食管条对卡巴胆碱、5-羟色胺的平滑肌反应降低，对氯化钾的反应增强。异丙肾上腺素和罂粟碱诱导的舒张反应不受影响。与对照组相比，CRF组中分离的LES条对氯化钾和卡巴胆碱的收缩力显著增加。CRF组和对照组中，异丙肾上腺素、SNP和罂粟碱刺激LES条产生的舒张反应相似。与对照组相比，CRF组中尼古丁诱导的舒张反应降低。
我们的研究揭示了CRF诱导大鼠中受体依赖性食管和LES平滑肌反应性的改变。前肠平滑肌反应性受损可能导致CRF患者出现与GER相关的功能异常。
