ROLE OF GASTRIC BLOOD-FLOW IN IMPAIRED DEFENSE AND REPAIR OF AGED RATSTOMACHS

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 NaC l for 10 min followed by saline (pH = 1.0) for 60 min in chambered sto machs. The lesion area was significantly larger and epithelial restitu tion was significantly slower in aged than in young rats after both ty pes of injury. Changes in gastric blood flow were monitored by laser-D oppler velocimetry. Young, but not aged, rats showed a marked increase in gastric blood flow in response to I M NaCl, acid challenge, and 64 0 mu M capsaicin for 60 min. Young rats showed a higher density of cal citonin gene-related peptide (CGRP)-staining nerve fibers around submu cosal blood vessels and higher mucosal release of prostaglandin E(2) a nd leukotriene C-4 than did aged rats. These data suggest that impaire d mucosal defense and reduced restitution in aged rats is related to l ack of hyperemic response caused by mucosal injury and H+ back-diffusi on, which is probably due to decreased density of CGRP-staining nerve fibers and prostaglandin biosynthetic capacity in the mucosa.