Angiotensin II type II receptors and colonic dysmotility in 2,4‐dinitrofluorobenzenesulfonic acid‐induced colitis in rats

Background Angiotensin II (Ang II), the main peptide of the renin‐angiotensin system (RAS), has been suggested to be involved in inflammatory bowel diseases. SinceRAShas emerged as gut motility regulator, and dysmotility is associated with intestinal inflammation, our objective was to investigate in rat 2,4‐dinitrobenzenesulfonic acid (DNBS)‐induced colitis the functionality ofRASand its contribution to colonic motor alterations. Methods The effects of Ang II on the longitudinal colonic muscular contractility of control andDNBS‐treated rats were characterizedin vitro. Transcripts encoding for Ang II receptors were investigated byRT‐PCR. Key Results Inflamed preparations showed a longitudinal muscle marked hypocontractility. Angiotensin II caused contractile effects in both preparations, but the responses inDNBSpreparations were reduced compared to controls. In both preparations, Losartan,AT1receptor antagonist, reduced Ang II effects.PD123319,AT2receptor antagonist, enhanced Ang II responses only inDNBSrats, as well as Nω‐Nitro‐L‐arginine (L‐NNA), nitric oxide (NO) synthase inhibitor, or tetrodotoxin (TTX), neural toxin. The co‐administration ofPD123319 andTTXor L‐NNAproduced no additive effects.PD123319per seimproved colonic contractility in inflamed tissues. The effect was reduced in the presence of L‐NNAorTTX. All Ang II receptor subtypes were expressed in both preparations. Conclusions & Inferences AT1receptors mediate Ang II contractile responses in rat colon. During inflammation a recruitment of Ang IIAT2receptors would counteractAT1‐contractile activity. A tonic activation ofAT2receptors would contribute to the general reduction in muscle contractility during experimental inflammation. A role for enteric neurons andNOis also suggested.