Interaction between the Renin-Angiotensin System and Enteric Neurotransmission Contributes to Colonic Dysmotility in the TNBS-Induced Model of Colitis

Autores da FMUP

• Teresa Maria De Jesus Teixeira De Sousa

  Autor

• Fernando José Magro Dias

  Autor

Participantes de fora da FMUP

• Ferreira-Duarte, M
• Rodrigues-Pinto, T
• Faria, MA
• Rocha, MS
• Menezes-Pinto, D
• Esteves-Monteiro, M
• Dias-Pereira, P
• Duarte-Araújo, M
• Morato, M

Unidades de investigação

• Biomedicina

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Angiotensin II (Ang II) regulates colon contraction, acting not only directly on smooth muscle but also indirectly, interfering with myenteric neuromodulation mediated by the activation of AT(1) /AT(2) receptors. In this article, we aimed to explore which mediators and cells were involved in Ang II-mediated colonic contraction in the TNBS-induced rat model of colitis. The contractile responses to Ang II were evaluated in distinct regions of the colon of control animals or animals with colitis in the absence and presence of different antagonists/inhibitors. Endogenous levels of Ang II in the colon were assessed by ELISA and the number of AT(1)/AT(2) receptors by qPCR. Ang II caused AT(1) receptor-mediated colonic contraction that was markedly decreased along the colons of TNBS-induced rats, consistent with reduced AT(1) mRNA expression. However, the effect mediated by Ang II is much more intricate, involving (in addition to smooth muscle cells and nerve terminals) ICC and EGC, which communicate by releasing ACh and NO in a complex mechanism that changes colitis, unveiling new therapeutic targets.

Keywords

• inflammatory bowel disease; IBD; TNBS-induced colitis; colonic dysmotility; angiotensin II; AT(1) and AT(2) receptors; nitric oxide; interstitial cells of Cajal; ICC; enteric glial cells; EGC