AJP - Gastrointestinal and Liver Physiology, Vol 270, Issue 1 71-G78, Copyright © 1996 by American Physiological Society

ARTICLES

Impairment of the gastric hyperemic response to luminal acid in cirrhotic rats

Y. Nishizaki, P. H. Guth, C. Sternini and J. D. Kaunitz
Medical Service, West Los Angeles Veterans Affairs Medical Center, California, USA.

Liver cirrhosis impairs gastric mucosal resistance to luminal acid in humans and in animal models. Because we have previously shown that pentagastrin enhances defensive as well as aggressive factors implicated in mucosal injury, we examined the hypothesis that the pentagastrin-mediated enhancement of mucosal defense mechanisms may be impaired in cirrhotic rats. Increased acid backdiffusion and susceptibility to gross mucosal injury, associated with an elimination of the hyperemic response to gastric barrier disruption, was observed in cirrhotic rats. In in vivo microscopic studies in anesthetized rats, cirrhosis had no effect on pentagastrin-associated enhancement of mucus gel thickness or baseline gastric mucosal blood flow, although baseline mucus gel thickness was decreased. Cirrhosis did, however, abolish the luminal acid-related hyperemic response to pentagastrin, which was associated with impaired intracellular pH homeostasis during acid superfusion. Cirrhosis did not alter submucosal calcitonin gene-related peptide immunoreactive nerves. We conclude that acid backdiffusion and pentagastrin-associated hyperemic responses are important mucosal defensive factors that are specifically impaired by cirrhosis.