EMA401, an angiotensin II type 2 receptor antagonist blocks visceral hypersensitivity and colonic hyperpermeability in rat model of irritable bowel syndrome

Visceral hypersensitivity and impaired gut barrier are crucial pathophysiology of irritable bowel syndrome (IBS), and injection of lipopolysaccharide or corticotropin-releasing factor, and repeated water avoidance stress simulate these gastrointestinal changes in rat (IBS models). We previously demonstrated that losartan, an angiotensin II type 1 (AT(1)) receptor antagonist prevented these changes, and we attempted to determine the effects of EMA401, an AT(2) receptor antagonist in the current study. EMA401 blocked visceral hypersensitivity and colonic hyperpermeability in these models, and naloxone reversed the effects by EMA401. These results suggest that EMA401 may improve gut function via opioid signaling in IBS. (C) 2021 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.

Automated summary

The study demonstrated that EMA401 may improve gut function in IBS through opioid signaling, blocking visceral hypersensitivity and colonic hypermeability. These findings provide a new potential treatment for IBS.