Developmental Differences in Neurohumoral Modulation of the Cat Lower Esophageal Sphincter

Abstract

ABSTk4CT. It is possible that age-related differences in gastroesophageal function during infancy may predispose the infant to abnormalities. We have therefore evaluated developmental differences in neurohumoral modulation of lower esophageal sphincter function in the cat. These studies were performed in an in vitro setting. In the adult cat, lower esophageal sphincter smooth muscle and postganglionic inhibitory neurons are more sensitive to muscarinic agonists than in the kitten. The circular smooth muscle of the adult lower esophageal sphincter is also more responsive to neurally mediated relaxation, brought about by electrical stimulation. However, there is no difference in response to exogenous vasoactive intestinal peptide between the two age groups. These data suggest that developmental differences in neurohumoral modulation of the lower esophageal sphincter occur in the cat. Studies of receptor activity in the LES during the newborn period would be of interest as GER is common during this period and decreases in frequency towards the end of the first year of life. Little attention, however, has been paid to modulation of LES activity during the newborn period. In vitro studies in the opossum ( 5 ) and in vivo studies in the beagle pup (6) suggest that the infant LES responds less than the adult to exogenous gastrin.The possibility that developmental differences in modulation of LES function may predispose the newborn LES to incompetence leads to the present investigation in which we propose to examine the development of neurohumoral modulation of LES pressure. Abbreviations MATERIALS AND METHODSGER, gastroesophageal reflux LES, lower esophageal sphincter TTX, tetrodotoxin VIP, vasoactive intestinal peptide DMPP, 1,l-Dimethyl-4-phenylpiperazinium iodidine GER is a common occurrence during infancy, resulting in significant morbidity (1). Although it is reasonable to expect that abnormalities in LES function may be the cause of infant GER, the developmental differences responsible for this phenomenon are unclear.The newborn infant undergoes many physiologic adaptations during development. We have recently shown that the kitten LES is unable to produce intraluminal pressure as high as the adult (2) despite being able to generate high amounts of stress in the LES circular muscle layer. This apparent contradiction is explained by the finding that the kitten LES has reduced thickness and thickness/radius ratio in the circular muscle layer, which causes a mechanical disadvantage in generating in vivo LES pressure.Cat LES tone, in vitro, is myogenic as it is not affected by TTX although LES relaxation is neurally mediated. In vivo LES C.H. is a recipient of NIH Grant 5R29-HD20054-02 and P.B. is a recipient of NIH Grant DK-RO 28614.Our study was performed on 6-wk-old recently weaned kittens and adult cats 3-5 kg in wt. After midline laparotomy, the LES was identified, and a suture was placed on the outer surface of the esophagus at the location of the high pressure zone as described previously (7).Stomach, LES, and...