Basic Research
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2005; 11(36): 5677-5684
Published online Sep 28, 2005. doi: 10.3748/wjg.v11.i36.5677
Role of nitric oxide in the impairment of circular muscle contractility of distended, uninflamed mid-colon in TNBS-induced acute distal colitis in rats
Luciano Onori, Annalisa Aggio, Simona D’Alo’, Paola Muzi, Maria Grazia Cifone, Gabriella Mellillo, Rachele Ciccocioppo, Gennaro Taddei, Giuseppe Frieri, Giovanni Latella
Luciano Onori, Annalisa Aggio, Rachele Ciccocioppo, Gennaro Taddei, Giuseppe Frieri, Giovanni Latella, Department of Internal Medicine and Public Health, University of L’ Aquila, 67100 L’Aquila, Italy
Simona D’Alo’, Paola Muzi, Maria Grazia Cifone, Department of Experimental Medicine, University of L’ Aquila , 67100 L’Aquila, Italy
Gabriella Mellillo, Department of Preclinical Pharmacology, Dompé SPA Research Center, 67100 L’Aquila, Italy
Author contributions: All authors contributed equally to the work.
Correspondence to: Giovanni Latella, MD, Dipartimento di Medicina Interna e Sanità Pubblica, Cattedra di Gastroenterologia, Università degli Studi di L’Aquila, Via S. Sisto n. 22/E, 67100 L’Aquila, Italy. giolatel@tin.it
Telephone: +39-862-433358 Fax: +39-862-432858
Received: December 19, 2004
Revised: February 13, 2005
Accepted: February 18, 2005
Published online: September 28, 2005
Abstract

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 tachykinergic neurokinin 1 and 2 receptors mediated transmission in DUMC of TNBS rats vs a simple additive interaction in controls.

CONCLUSION: The results of this study show that, during TNBS-induced acute distal colitis, circular muscle intrinsic contractile mechanisms and possible enteric neural excitatory activity are inhibited in the distended uninflamed mid-colon. Suppression of NO synthesis markedly improves spontaneous and evokes muscle contractions, in spite of any evident change in local NO activity.

Keywords: TNBS colitis, Colonic dilatation, Colonic motility, Nitric oxide synthase