ROLE OF HISTAMINE AND CALCITONIN-GENE-RELATED PEPTIDE IN THE HYPEREMIC RESPONSE TO HYPERTONIC SALINE AND H-DIFFUSION IN THE GASTRIC-MUCOSA OF CATS( BACK)

Background: The present study was undertaken to measure the output of histamine and calcitonin gene-related peptide (CGRP) from injured and restituting gastric mucosa into venous blood and to study the effect o f acid back-diffusion on the release of these mediators and their role in the hyperemic response to injury. Methods: Stomachs of cats were p erfused with saline at pH 1.0 or 7.4. Gastric mucosal blood flow (GMBF ) was determined with radioactive microspheres, and blood flow in the portal vein and celiac artery was determined by transit-time flowmetry . H+ back-diffusion/secretion was measured by pH-stat titration and by measuring the arteriovenous base excess difference. Mucosal injury wa s produced by exposure to 2M NaCl. Histamine and CGRP in portal venous blood were measured by radioimmunoassay. Results: During mucosal expo sure to 2M NaCl GMBF increased, and histamine (0.23 nmol/min) and CGRP (1.2 pmol/min) were released from the mucosa into blood. The hyperemi c response was reduced by pretreatment with H-1 and H-2 blockers and s till further by addition of the blocker CGRP(8-37). After mucosal dama ge and luminal perfusion at pH 7.4, GMBF and output of CGRP and histam ine decreased towards base-line levels within 30 min. During luminal p erfusion at pH 1.0 associated with acid back-diffusion, GMBF and hista mine output remained high, whereas the output of CGRP decreased to bas e-line level. Pretreatment with H-1 and H-2 blockers reduced the hyper emic response as measured 30 min after damage. Conclusions: The hypere mic response caused by 2 M NaCl is most likely mediated by histamine a nd CGRP and maintained by histamine released by back-diffusion of H+ t hrough the superficially damaged gastric mucosa.