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

AbstractBackground: Angiotensin II (Ang II), the main peptide of the renin-angiotensinsystem(RAS), has been suggested to be involved in inflammatory bowel diseases. Since RAShas emerged as gut motility regulator, and dysmotility is associated with intestinal inflammation,our objective was to investigate in rat 2,4-dinitrobenzenesulfonicacid(DNBS)-inducedcolitis the functionality of RAS and its contribution to colonic motoralterations.Methods: The effects of Ang II on the longitudinal colonic muscular contractility ofcontrol and DNBS-treated rats were characterized in vitro. Transcripts encoding forAng 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 responsesin DNBS preparations were reduced compared to controls. In bothpreparations, Losartan, AT1 receptor antagonist, reduced Ang II effects. PD123319,AT2 receptor antagonist, enhanced Ang II responses only in DNBS rats, as well as N?-Nitro-L-arginine(L-NNA),nitric oxide (NO) synthase inhibitor, or tetrodotoxin (TTX),neural toxin. The co-administrationof PD123319 and TTX or L-NNAproduced noadditive effects. PD123319 per se improved colonic contractility in inflamed tissues.The effect was reduced in the presence of L-NNAor TTX. All Ang II receptor subtypeswere expressed in both preparations.Conclusions & Inferences: AT1 receptors mediate Ang II contractile responses in ratcolon. During inflammation a recruitment of Ang II AT2 receptors would counteractAT1-contractileactivity. A tonic activation of AT2 receptors would contribute to thegeneral reduction in muscle contractility during