Angiotensin II subtype 1 receptor blockade inhibits Clostridium difficile toxin A-induced intestinal secretion in a rabbit model

Angiotensin II ( ANG II) has been described in the regulation of intestinal secretion and absorption via angiotensin subtype 1 ( AT 1) and AT 2 receptors, respectively, in rats. We investigated the role that ANG II plays in the rabbit ileal-loop model of Clostridium difficile infection. Expression of AT 1, the more abundant ANG II receptor, was demonstrated in ileal loops, and an AT 1 receptor blocker, losartan, inhibited hypersecretion induced by C. difficile toxin A ( mean volume: length ratio, vs. mL/cm in controls). 0.27 +/- 0.06 vs. 0.60 +/- 0.06 Losartan also decreased production of ANG II in the ileum (vs. pg/mg in controls), (0.48 +/- 0.06 vs. 0.87 +/- 0.12 raising the possibility that ANG II may participate in a positive feedback loop involving the hypersecretory response. Our findings suggest that ANG II plays a significant role in the pathogenesis of C. difficile toxin induced diarrhea.