Role of histamine and calcitonin gene-related peptide in the hyperemic response to hypertonic saline and H+ back-diffusion in the gastric mucosa of cats.

Abstract

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 of acid back-diffusion on the release of these mediators and their role in the hyperemic response to injury. Stomachs of cats were perfused 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 was produced by exposure to 2 M NaCl. Histamine and CGRP in portal venous blood were measured by radioimmunoassay. During mucosal exposure to 2 M NaCl GMBF increased, and histamine (0.23 nmol/min) and CGRP (1.2 pmol/min) were released from the mucosa into blood. The hyperemic response was reduced by pretreatment with H1 and H2 blockers and still further by addition of the blocker CGRP8-37. After mucosal damage and luminal perfusion at pH 7.4, GMBF and output of CGRP and histamine decreased towards base-line levels within 30 min. During luminal perfusion at pH 1.0 associated with acid back-diffusion, GMBF and histamine output remained high, whereas the output of CGRP decreased to base-line level. Pretreatment with H1 and H2 blockers reduced the hyperemic response as measured 30 min after damage. The hyperemic response caused by 2 M NaCl is most likely mediated by histamine and CGRP and maintained by histamine released by back-diffusion of H+ through the superficially damaged gastric mucosa.