Esophageal mucosal blood flow: A central role for calcitonin gene-related peptide

Background. Esophageal mucosal blood flow is a dynamic phenomenon dependent on luminal content. Reactive hyperemia, likely a factor in mucosal protection, follows luminal exposure to noxious substances, including bile. The mediators of this response are unknown, although the likelihood is that visceral afferent nerves play a major role. The purpose of this study was to determine whether substance P. calcitonin gene-related peptide (CGRP), or adenosine could mediate this reactive blood flow response. Methods. Esophageal mucosal blood flow was studied in a rabbit model with the radiolabeled microsphere technique. The effect of intraarterial infusion of CGRP and substance P and intravenous adenosine was studied. Subsequently, the hyperemic response to luminal deoxycholate was measured in the presence of antagonists to CGRP, substance P, and adenosine. Immunohistochemical studies were performed to determine the distribution of CGRP and substance P in the esophagus. Results. CGRP proved to be a potent stimulus to mucosal blood flow. The presence of a CGRP antagonist reduced mucosal blood flow at baseline and after exposure to deoxycholate. Antagonists to substance P and adenosine had no effect on baseline and deoxycholate-stimulated blood flow. Conclusions. CGRP is likely a major mediator involved in the regulation of esophageal mucosal blood flow.