An enteric signal regulates putative gastrointestinal presympathetic vasomotor neurons in rats

Abstract

Sartor, Daniela M., Arthur Shulkes, and Anthony J. M. Verberne. An enteric signal regulates putative gastrointestinal presympathetic vasomotor neurons in rats. Am J Physiol Regul Integr Comp Physiol 290: R625-R633, 2006. First published October 20, 2005 doi:10.1152/ajpregu.00639.2005.-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 CCKsensitive 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 GASTROINTESTINAL HYPEREMIA is a physiological consequence of food consumption. Gastrointestinal hormones such as cholecystokinin (CCK) have been implicated in gastrointestinal vasodilatation associated with postprandial increase in splanchnic blood flow. The involvement of the sympathetic vasomotor system in this response is poorly understood. We recently suggested that food-related signals may produce gastrointestinal vasodilatation via a reflex withdrawal of sympathetic vasomotor outflow (39,45). In healthy individuals, the sympathetic nervous system compensates for postprandial splanchnic blood pooling by activating sympathetic vasoconstrictor drive to skeletal muscle resistance vessels in response to baroreceptor unloading. In patients with cardiovascular disease associated with diabetic neuropathy or autonomic dysfunction, poor baroreflex comp...

Gastric leptin: a novel role in cardiovascular regulation

“…Extracellular single-unit recording of RVLM presympathetic neurons was performed as described previously (30,34,35). Only neurons that were barosensitive and spinally projecting were studied further.…”

“…Only neurons that were barosensitive and spinally projecting were studied further. Spinally projecting neurons were identified using antidromic activation and the collision test (30,34,35). AP, HR, and sympathetic nerve and single-unit responses to baroreflex activation (aortic occlusion or PE; 5-10 g/kg iv) and/or unloading [sodium nitroprusside (SNP), 5 g/kg], and the CCK-induced gastrointestinal circulatory reflex (CCK; 1-4 g/kg iv) were tested just prior to close arterial saline administration and/or close arterial leptin administration (15-30 g/kg).…”

“…AP, HR, and sympathetic nerve and single-unit responses to baroreflex activation (aortic occlusion or PE; 5-10 g/kg iv) and/or unloading [sodium nitroprusside (SNP), 5 g/kg], and the CCK-induced gastrointestinal circulatory reflex (CCK; 1-4 g/kg iv) were tested just prior to close arterial saline administration and/or close arterial leptin administration (15-30 g/kg). Doses of CCK, SNP, and PE used in this study were submaximal, as determined previously (30,34,35,39). Axonal conduction velocities (CV) were calculated by dividing the straight line distance (in meters) between the recording and spinal stimulating electrodes by the antidromic latency (in seconds).…”

“…AP, HR, SND, and extracellular unit discharge were recorded using a computerized data acquisition system (Cambridge Electronic Design, Cambridge, UK) and Spike2 software and analyzed as described previously (30,34,35).…”

“…Therefore, the aim of this study was to examine the acute effects of leptin administered within the gastrointestinal circulation (termed close arterial; to mimic the effects of gastric leptin) on cardiovascular regulation. We examined the effects of leptin administration on arterial pressure and heart rate (HR), splanchnic and lumbar SND, and the activity of different subpopulations of RVLM presympathetic vasomotor neurons discriminated by their sensitivity to CCK (30,34,35,38). Since leptin in the gastrointestinal tract may promote CCK release (11,12), an additional aim was to determine the involvement of CCK 1 receptors in the cardiovascular response to leptin and to determine whether this was dependent on vagal afferent transmission.…”