Angiotensin II Subtype 1 Receptor Blockade InhibitsClostridium difficileToxin A–Induced Intestinal Secretion in a Rabbit Model
| Autor: | Benedito A. Carneiro-Filho, Richard L. Guerrant, Gerly Anne de Castro Brito, Robert M. Carey, Leah J. Barrett, Cirle Alcantara, Xiao Hong Jin |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Bacterial Toxins
Clostridium difficile toxin A Clostridium difficile toxin B Biology medicine.disease_cause Losartan Microbiology Enterotoxins medicine Animals Immunology and Allergy Intestinal Mucosa Colitis Angiotensin II receptor type 1 Dose-Response Relationship Drug Clostridioides difficile Toxin Angiotensin II Ileitis Clostridium difficile medicine.disease Infectious Diseases Rabbits Angiotensin II Type 1 Receptor Blockers hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | The Journal of Infectious Diseases. 191:2090-2096 |
| ISSN: | 1537-6613 0022-1899 |
| DOI: | 10.1086/430316 |
| Popis: | Angiotensin II (ANG II) has been described in the regulation of intestinal secretion and absorption via angiotensin subtype 1 (AT1) and AT2 receptors, respectively, in rats. We investigated the role that ANG II plays in the rabbit ileal-loop model of Clostridium difficile infection. Expression of AT1, the more abundant ANG II receptor, was demonstrated in ileal loops, and an AT1 receptor blocker, losartan, inhibited hypersecretion induced by C. difficile toxin A (mean volume:length ratio, vs. mL/cm in controls). 0.27 � 0.06 0.60 � 0.06 Losartan also decreased production of ANG II in the ileum ( vs. pg/mg in controls), 0.48 � 0.06 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. Toxigenic Clostridium difficile is the most important known cause of both antibiotic-associated and nosocomial diarrhea. The clinical manifestations of C. difficile colitis are caused by either one or both of the large exotoxins—toxins A and B—secreted by C. difficile. Most of the inflammatory and secretory effects of C. difficile are due to toxin A, an enterotoxin. Toxin A has been shown to cause the release of inflammatory cytokines, the recruitment of polymorphonuclear cells, and the stimulation of prostaglandin synthesis [1–3]. Toxin B, however, is a cytotoxin that causes cytopathic changes in cell culture. Recent studies have implicated toxin A– negative/toxin B–positive strains of C. difficile as a cause of disease outbreaks [4]. Both toxin A and toxin B exert |
| Databáze: | OpenAIRE |
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