IMPAIRMENT OF THE GASTRIC HYPEREMIC RESPONSE TO LUMINAL ACID IN CIRRHOTIC RATS

Liver cirrhosis impairs gastric mucosal resistance to luminal acid in humans and in animal models. Because we have previously shown that pen tagastrin enhances defensive as well as aggressive factors implicated in mucosal injury, we examined the hypothesis that the pentagastrin-me diated enhancement of mucosal defense mechanisms may be impaired in ci rrhotic rats. Increased acid backdiffusion and susceptibility to gross mucosal injury, associated with an elimination of the hyperemic respo nse to gastric barrier disruption, was observed in cirrhotic rats. In in vivo microscopic studies in anesthetized rats, cirrhosis had no eff ect on pentagastrin-associated enhancement of mucus gel thickness or b aseline gastric mucosal blood flow although baseline mucus gel thickne ss was decreased. Cirrhosis did, however, abolish the luminal acid-rel ated hyperemic response to pentagastrin, which was associated with imp aired intracellular pH homeostasis:during acid superfusion. Cirrhosis did not alter submucosal calcitonin gene-related peptide immunoreactiv e nerves. We conclude that acid backdiffusion and pentagastrin-associa ted hyperemic responses are important mucosal defensive factors that a re specifically impaired by cirrhosis.