title: Angiotensin II subtype 1 receptor blockade inhibits Clostridium difficile toxin A-induced intestinal secretion in a rabbit model.
abstract: 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, 0.27+/-0.06 vs. 0.60+/-0.06 mL/cm in controls). Losartan also decreased production of ANG II in the ileum (0.48+/-0.06 vs. 0.87+/-0.12 pg/mg in controls), 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.
authors.affiliation: Center for Global Health, Division of Infectious Disease and International Health, University of Virginia, Charlottesville, Virginia 22903, USA.
authors.forename: Cirle S
authors.initials: CS
authors.lastname: Alcantara
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Jin
authors.forename: Gerly Anne C
authors.initials: GA
authors.lastname: Brito
authors.forename: Benedito A
authors.initials: BA
authors.lastname: Carneiro-Filho
authors.forename: Leah J
authors.initials: LJ
authors.lastname: Barrett
authors.forename: Robert M
authors.initials: RM
authors.lastname: Carey
authors.forename: Richard L
authors.initials: RL
authors.lastname: Guerrant
mesh_terms: D000804:Angiotensin II / Q000096:biosynthesis; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D016360:Clostridioides difficile; D004305:Dose-Response Relationship, Drug; D004768:Enterotoxins / Q000037:antagonists & inhibitors*; D007079:Ileitis / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019808:Losartan / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; D000804:Angiotensin II; D019808:Losartan