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Angiotensin II type-2 receptors and colonic dysmotility associated to experimental colitis in rats

  • Autori: M. G. Zizzo ; M. Auteri; A. Amato; G. Caldara; D. Nuzzo;, M. Di Carlo; R. Serio
  • Anno di pubblicazione: 2016
  • Tipologia: Abstract in atti di convegno pubblicato in volume
  • OA Link:


Angiotensin II (Ang II) is a newly discovered modulator of intestinal motility, mainly via activation of excitatory AT1 receptors (AT1R). We demonstrated that during gut inflammation there is a recruitment of inhibitory AT2 receptors (AT2R) which would counteract the AT1R-induced effects. Our objective was to explore the consequence of AT2R activation in the pathogenesis of experimental colitis. Colitis was induced in rats by intrarectal administration of 2,4-Dinitrobenzene sulfonic acid (DNBS). Colonic damage was assessed by macro- and microscopic scores, myeloperoxidase activity and inflammatory cytokine expression on day 6 after colitis induction. Colonic contractility was recorded in vitro. In a separate group of animals, the effects of 6-day intraperitoneal treatment with PD123319 (3 mg/kg) on colitis features were examined. Colon from DNBS-rats showed marked inflammation associated to a decrease of spontaneous and evoked mechanical activity. Ang II contractile response was reduced by the activation of inhibitory AT2 receptors. PD123319, AT2R antagonist, per se ameliorated colonic contractility. Inhibition of nitric oxide synthase or neural activity induced as well an increase of contractility in DNBS preparations. In such conditions PD123319 did not induce further effects. In DNBS rats daily i.p. treatment with PD123319, attenuated colitis severity, reducing body weight loss and incidence of diarrhoea and improving mechanical activity in vitro. In conclusion, during inflammation constitutively activated AT2 receptors via involvement of enteric nerves and NO would contribute to the reduction of muscle contractility. Blocking AT2R activation in vivo seems to improve some symptoms during intestinal inflammation, driving future study.