No abstract

Summary Background: Capsaicin acts specifically on primary afferent neurones to release neuropeptides, including calcitonin gene‐related peptide (CGRP), and prevents ethanol‐induced mucosal injury. Aim: To investigate the microvascular changes in the gastric mucosa in response to ethanol using intravital microscopy to elucidate the mechanism of capsaicin‐induced gastroprotection. Methods: The posterior gastric wall in the rat was secured in an observation chamber and perfused with Tyrode's solution. The microcirculation was observed through a window made by removing a limited area of smooth muscle. Results: Ethanol (50%) applied to the mucosa constricted the collecting venules and venules but dilated arterioles. The constriction of the collecting venules resulted in mucosal congestion, which caused mucosal injury. Application of capsaicin to the mucosa dilated the arterioles but not the collecting venules or venules. Arteriolar dilation was inhibited by a CGRP antagonist, CGRP‐(8–37). Prior application of capsaicin prevented ethanol‐induced constriction of the collecting venules, and the action of capsaicin was inhibited by prior application of CGRP‐(8–37). Conclusions: The results suggest that the inhibition of ethanol‐induced gastric injury by capsaicin is attributable to the suppression of collecting venule constriction, via CGRP release.

ABSTRACT-Pre-exposure of the rat gastric mucosa to capsaicin reduced the mucosal lesion by 50% ethanol to 1/4. Treatment with an antagonist of calcitonin gene-related peptide (CGRP), CGRP (8 -37), nullified the effect of capsaicin. During constant perfusion of the gastric lumen with physiological saline + pepstatin, the CGRP level was not increased by 50% ethanol, but it showed a peak (802.5 ± 145.7 pg /2 min) after 1.6 mM capsaicin. Four minutes after capsaicin, the CGRP level was kept at a high level and the gastric lesion was markedly reduced by re-exposure of the mucosa to 50% ethanol. At 20 -30 min after capsaicin, the CGRP levels returned to the resting level and the reddened area by 50% ethanol was not reduced. It was concluded that capsaicin transiently prevented the mucosal lesion through CGRP release.

These results suggest that PGE2 dilated both arterioles and venules in the rat gastric mucosa through the EP2 receptors and constricted the venules through the EP3 receptors.