Neuropeptide release from the isolated, perfused, lower esophageal sphincter region of the rabbit and the effect of vasoactive intestinal peptide on the sphincter

Background. The aim was to evaluate the isolated, vascularly perfused, lower esophageal sphincter (LES) as a model for investigating the functional role of neuropeptides such as vasoactive intestinal peptide (VIP). Methods. At laparotomy the LES was removed along with the distal esophagus, stomach, and left gastric artery and vein. The LES area, isolated from the body of the stomach by a custom-made clamp, was perfused with oxygenated Krebs-Ringer bicarbonate solution (pH 7.4, 38 ° C) via the left gastric artery. The LES pressure was monitored continuously with a custom-made Dent sleeve catheter. LES pressure and release of neuropeptides were investigated after carbachol and VIP were administered alone or in combination. VIP, calcitonin gene-related peptide (CGRP), and somatostatin were measured in the venous perfusate collected from the left gastric vein. Results. LES tone and contraction frequency were similarly increased by 10 and 100 nmol/L carbachol (increment, 4.0 ± 0.26 mm Hg with 10 nmol/L carbacho1; p < 0.0003). Perfusion with 10 nmol/L VIP decreased basal tone and completely abolished the contraction induced by 100 nmol/L carbachol. VIP, CGRP, and somatostatin were released from the LES in response to 10 nmol/L carbachol (VIP rose from 55 ± 13 to 179 ± 24 pmol/L, CGRP from 114 ± 30 to 239 ± 33 pmol/L, and somatostatin from 15 ± 2 to 27 ± 4 pmol/L; all p < 0.001). Conclusions. These findings support a role for VIP in the inhibitory reflex of the LES but suggest that other neuropeptides may also be involved. The isolated, perfused LES provides a new tool for investigating neuropeptide interactions.