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 degrees 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 carbachol; p less than 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 less than 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.
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 degrees 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 carbachol; p less than 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 less than 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.