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

2017; Wiley; Volume: 29; Issue: 6 Linguagem: Inglês

10.1111/nmo.13019

1365-2982

Maria Grazia Zizzo, Michelangelo Auteri, Antonella Amato, G Caldara, Domenico Nuzzo, Marta Di Carlo, Rosa Serio,

Receptor Mechanisms and Signaling

Abstract Background Angiotensin II (Ang II), the main peptide of the renin‐angiotensin system ( RAS ), has been suggested to be involved in inflammatory bowel diseases. Since RAS has 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 of RAS and its contribution to colonic motor alterations. Methods The effects of Ang II on the longitudinal colonic muscular contractility of control and DNBS ‐treated rats were characterized in vitro . Transcripts encoding for Ang II receptors were investigated by RT ‐ PCR . Key Results Inflamed preparations showed a longitudinal muscle marked hypocontractility. Angiotensin II caused contractile effects in both preparations, but the responses in DNBS preparations were reduced compared to controls. In both preparations, Losartan, AT 1 receptor antagonist, reduced Ang II effects. PD 123319, AT 2 receptor antagonist, enhanced Ang II responses only in DNBS rats, as well as N ω ‐Nitro‐L‐arginine (L‐ NNA ), nitric oxide ( NO ) synthase inhibitor, or tetrodotoxin ( TTX ), neural toxin. The co‐administration of PD 123319 and TTX or L‐ NNA produced no additive effects. PD 123319 per se improved colonic contractility in inflamed tissues. The effect was reduced in the presence of L‐ NNA or TTX . All Ang II receptor subtypes were expressed in both preparations. Conclusions & Inferences AT 1 receptors mediate Ang II contractile responses in rat colon. During inflammation a recruitment of Ang II AT 2 receptors would counteract AT 1 ‐contractile activity. A tonic activation of AT 2 receptors would contribute to the general reduction in muscle contractility during experimental inflammation. A role for enteric neurons and NO is also suggested.