Role of gastric blood flow in impaired defense and repair of aged rat stomachs.

To study impaired gastric mucosal tolerance against noxious agents in aged rats, possible factors underlying this observation were compared in anesthetized Fisher 344 young and aged rats. The gastric mucosa was damaged by in situ exposure to 80% ethanol for 30-45 s and by 1 M NaCl for 10 min followed by saline (pH = 1.0) for 60 min in chambered stomachs. The lesion area was significantly larger and epithelial restitution was significantly slower in aged than in young rats after both types of injury. Changes in gastric blood flow were monitored by laser-Doppler velocimetry. Young, but not aged, rats showed a marked increase in gastric blood flow in response to 1 M NaCl, acid challenge, and 640 microM capsaicin for 60 min. Young rats showed a higher density of calcitonin gene-related peptide (CGRP)-staining nerve fibers around submucosal blood vessels and higher mucosal release of prostaglandin E2 and leukotriene C4 than did aged rats. These data suggest that impaired mucosal defense and reduced restitution in aged rats is related to lack of hyperemic response caused by mucosal injury and H+ back-diffusion, which is probably due to decreased density of CGRP-staining nerve fibers and prostaglandin biosynthetic capacity in the mucosa.