Role of nitric oxide in the impairment of circular muscle contractility of distended, uninflamed mid-colon in TNBS-induced acute distal colitis in rats
Role of nitric oxide in the impairment of circular muscle contractility of distended, uninflamed mid-colon in TNBS-induced acute distal colitis in rats作者机构：Department of Internal Medicine and Public Health University of L' Aquila 67100 L'Aquila Italy Department of Experimental Medicine University of L' Aquila 67100 L'AquilaItaly Department of Preclinical Pharmacology Dompě SPA Research Center 67100 L'Aquila Italy
出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)
年 卷 期：2005年第11卷第36期
页 面：5677-5684页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
主 题：TNBS colitis Colonic dilatation Colonic motility Nitric oxide synthase
摘 要：AIM： To evaluate the role of nitric oxide （NO） in the motor disorders of the dilated uninflamed mid-colon （DUMC） from trinitrobenzene sulfonic acid （TNBS）-induced acute distal colitis in rats. METHODS： Colitis was induced in male Sprague-Dawley rats by a single intracolonic administration of TNBS. Control rats received an enema of 0.9% saline. The rats were killed 48 h after TNBS or saline administration. Macroscopic and histologic lesions of the colon were evaluated. Myeloperoxidase （MPO） and nitric oxide synthase （NOS） activity were measured on the colonic tissue. In TNBS rats, we evaluated spontaneous and evoked contractile activity in circular muscle strips derived from DUMC in comparison to the same colonic segment of control rats, both in the presence and in the absence of a non-selective NOS isoforms inhibitor N-nitro-L- arginine （L-NNA）. Pharmacological characterization of electric field stimulation （EFS）-evoked contractile responses was also performed. RESULTS： In TNBS rats, the distal colon showed severe histological lesions and a high MPO activity, while the DUMC exhibited normal histology and MPO activity. Constitutive NOS activity was similar in TNBS and control rats, whereas inducible NOS activity was significantly increased only in the injured distal colon of TNBS rats. Isometrically recorded mechanical activity of circular muscle strips from DUMC of TNBS rats showed a marked reduction of the force and frequency of spontaneous contractions compared to controls, as well as of the contractile responses to a contracting stimulus. In the presence of L-NNA, the contractile activity and responses displayed a significantly greater enhancement compared to controls. The pharmacological characterization of EFS contractile responses showed that a cooperative-like interaction between cholinergic muscarinic and tachyldnergic neurokinin 1 and 2 receptors mediated transmission in DUMC of TNBS rats vs a simple additive interaction in controls. CONCLUSION： The results
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