ANG II Type 1 Receptor Blockade May Curb C. Difficile-Induced Diarrhea

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ANG II Type 1 Receptor Blockade May Curb C. Difficile-Induced Diarrhea

Reuters Health Information 2005. © 2005 Reuters Ltd.

NEW YORK (Reuters Health) Jun 24 - Studies in rabbits show that Clostridium difficile toxin A leads to enhanced expression of angiotensin II (ANG II), which, in turn, mediates mucosal injury and intestinal hypersecretion through angiotensin subtype 1 receptors (AT1).

The studies also show that AT1 receptor blockade with the ANG II antagonist losartan inhibits the inflammatory and secretory cascade brought on by C. difficile toxin A.

"Our findings suggest that ANG II plays a significant role in the pathogenesis of C. difficile toxin-induced diarrhea," investigators write in the June 15th issue of The Journal of Infectious Diseases.

In the rabbit ileum, Dr. L. Guerrant from the University of Virginia Health Sciences Center in Charlottesville and colleagues observed that C. difficile infection "induced severe mucosal injury, invoked an intense inflammatory reaction and augmented intestinal secretion." They also observed elevated levels of ANG II and the presence of AT1 receptors in the presence of C. difficile toxin A in rabbit ileal tissue.

Blocking the AT1 receptor with losartan inhibited the hypersecretory response to C. difficile toxin A and also led to a concomitant decrease in ANG II levels.

Pharmacologic inhibition of AT1 receptors "provides a potentially novel approach to control of C. difficile-associated diarrhea and C. difficile colitis," the investigators conclude.

J Infect Dis 2005;191:2090-2096.