An enteric signal regulates putative gastrointestinal presympathetic vasomotor neurons in rats

1 Clinical Pharmacology and Therapeutics Unit, Department of Medicine, and 2 Department of Surgery, University of Melbourne, Austin Health, Heidelberg Victoria, Australia Submitted 31 August 2005 ; accepted in final form 19 October 2005 Ingestion of a meal results in gastrointestinal (GI) hyperemia and is associated with systemic and paracrine release of a number of peptide hormones, including cholecystokinin (CCK) and 5-hydroxytryptamine (5-HT). Systemic administration of CCK octapeptide inhibits a subset of presympathetic neurons of the rostroventrolateral medulla (RVLM) that may be responsible for driving the sympathetic vasomotor tone to the GI viscera. The aim of this study was to determine whether endogenous release of CCK and/or 5-HT also inhibits CCK-sensitive RVLM neurons. The effects of intraduodenal administration of the secretagogues sodium oleate (SO) and soybean trypsin inhibitor (SBTI) on circulating levels of CCK and 5-HT were examined. In separate experiments, the discharge rates of barosensitive, medullospinal, CCK-sensitive RVLM presympathetic vasomotor neurons were recorded after rapid intraduodenal infusion of SO-SBTI or water. Alternatively, animals were pretreated with the CCK 1 receptor antagonists devazepide and lorglumide or the 5-HT 3 antagonist MDL-72222 before SO-SBTI administration. Secretagogue infusion significantly increased the level of circulating CCK, but not 5-HT. SO-SBTI significantly decreased (58%) the neuronal firing rate of CCK-sensitive RVLM neurons compared with water (5%). CCK 1 receptor antagonists did not reverse SO-SBTI-induced neuronal inhibition (58%), whereas the 5-HT 3 antagonist significantly attenuated the effect (22%). This study demonstrates a functional relation between a subset of RVLM presympathetic vasomotor neurons and meal-related signals arising from the GI tract. It is likely that endogenously released 5-HT acts in a paracrine fashion on GI 5-HT 3 receptors to initiate reflex inhibition of these neurons, resulting in GI vasodilatation by withdrawal of sympathetic tone. rostroventrolateral medulla; cholecystokinin; devazepide; MDL-72222; 5-hydroxytryptamine Address for reprint requests and other correspondence: D. M. Sartor, Univ. of Melbourne, Clinical Pharmacology and Therapeutics Unit, Dept. of Medicine, Austin Health, Heidelberg, Victoria 3084, Australia (e-mail: dsartor{at}unimelb.edu.au )