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Dysregulation of different mediator systems could contribute to the gut dismotility in inflammatory boweldiseases (IBDs), chronic disorders characterized by an exasperated immune response disturbing gutfunctions. Among these, Angiotensin II (Ang II), the main peptide of renin-angiotensin system (RAS), canparticipate in inflammatory responses and RAS components are increased in IBD patients. Since RAS hasemerged as gut motility regulator, our objectives was to investigate, in an IBD rat model, the RASfunctionality and its eventual contribution to colonic dismotility. Experimental colitis was induced in ratsby intracolonic administration of 2,4-dinitrobenzenesulfonic acid (DNBS). Drug effects on the longitudinalcolonic muscular contractility of normal and DNBS-treated rats were characterised in vitro, using organbath-technique. Colonic preparations from DNBS rats, showed a low in amplitude spontaneous activity and adepressed responsiveness to pharmacological agents, such as the cholinergic agonist, carbachol and the β-adrenergic receptor agonist isoproterenol, compared to normal rats. Ang II induced muscular contraction in normal and inflammatory conditions, whose amplitude was decreased in DNBS rats. In both preparations theAT1 receptor antagonist, losartan, reduced Ang II effects. The AT2 receptor antagonist, PD123319,ineffective in control rats, enhanced Ang II contractile responses in DNBS rats. The neural toxin, TTX andL-NNA, NO synthase inhibitor, were ineffective in control rats, but increased contractile response in DNBSrats. The joint application of PD123319 and TTX or L-NNA did not have additive effects. Interestingly,PD123319 improved the spontaneous activity and carbachol and isoproterenol responses in DNBS animals.In conclusion, Ang II contracts rat colonic longitudinal muscle via post-junctional AT1 receptors. Underbowel inflammation AT2 receptor recruitment, likely on inhibitory nitrergic neurons, decreases coloniccontractility and would counteract AT1 activity. Pharmacological manipulation of RAS system could beconsidered in the attempt to improve the treatment of intestinal dismotility in IBDs.
Original languageEnglish
Number of pages2
Publication statusPublished - 2015

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