Phenotypic identification of rat rostroventrolateral medullary presympathetic vasomotor neurons inhibited by exogenous cholecystokinin

Abstract

Systemic administration of the gastrointestinal hormone cholecystokinin (CCK) selectively inhibits splanchnic sympathetic vasomotor discharge and differentially affects presympathetic vasomotor neurons of the rostroventrolateral medulla (RVLM). Stimulation of the sympathoexcitatory region of the periaqueductal grey (PAG) produces profound mesenteric vasoconstriction. In this study, our aim was to identify phenotypically different populations of RVLM presympathetic vasomotor neurons using juxtacellular neuronal labelling and immunohistochemical detection of the adrenergic neuronal marker phenylethanolamine-N-methyl transferase (PNMT) and to determine whether the PAG provides functional excitatory input to these neurons. Fifty-eight percent (36/62) of RVLM presympathetic neurons were inhibited by systemic administration of CCK. These cells had conduction velocities (3.6 +/- 0.2 m/sec) in the non-C-fiber range consistent with neurons possessing lightly myelinated spinal axons. Of these, 79% (22/28) were excited by PAG stimulation, and 59% (10/17) were not immunoreactive for PNMT. Conversely, 42% (26/62) of RVLM presympathetic neurons were either unaffected or activated by CCK administration and had slower conduction velocities (1.4 +/- 0.3 m/sec) than cells inhibited by CCK. Fifty percent (11/22) of these cells were driven by PAG stimulation, and most (11/14 or 79%) were PNMT-positive. These results suggest that cardiovascular responses elicited by PAG stimulation occur via activation of non-C1 and C1 RVLM presympathetic neurons. RVLM neurons inhibited by CCK were more likely to be driven by PAG stimulation and may be a subset of neurons responsible for driving gastrointestinal sympathetic vasomotor tone. CCK-induced inhibition of a subpopulation of RVLM presympathetic neurons may be implicated in postprandial hyperemia and postprandial hypotension.

An enteric signal regulates putative gastrointestinal presympathetic vasomotor neurons in rats

“…We previously demonstrated that systemic administration of exogenous CCK inhibits the firing rate of a subpopulation of RVLM presympathetic (termed CCK-sensitive) neurons (39,40). On the basis of these observations, we predicted that simulation of postprandial conditions by infusion of secretagogues into the duodenum would also inhibit CCK-sensitive RVLM presympathetic vasomotor neurons, and this hypothesis was tested in the present study.…”

“…Arterial and venous cannulation of male Sprague-Dawley rats for the measurement of arterial blood pressure and for intravenous drug administration, respectively, was carried out as described previously (39,40). Briefly, rats were anesthetized with halothane, tracheostomized, and ventilated with 100% O 2 containing 1.3-1.5% halothane (50 -60 breaths/min, 1 ml/kg).…”

“…An intracellular amplifier in bridge mode (Intra 767, World Precision Instruments, Sarasota, FL) was used for recordings, and a window discriminator (Fintronics, Orange, CT) was used for signal amplification (400 Hz-4 kHz band pass); an oscilloscope and audio amplifier were used to monitor extracellularly recorded signals. The procedures used for location, identification, and extracellular single-unit recording of RVLM neurons have been described previously (39,40). Before neuronal recording, an inflatable occlusive cuff was placed on the abdominal aorta for precisely controlled elevation of arterial blood pressure for baroreceptor stimulation.…”

“…Intravenous administration of CCK sulfated octapeptide (CCK-8) selectively inhibits splanchnic, but not lumbar, sympathetic nerve activity (39) and is also selective for a subset of barosensitive neurons in the RVLM (39,40). Postprandially released CCK may act in a paracrine fashion on subdiaphragmatic vagal afferent fibers (38) within the wall of the gastrointestinal mucosa to indirectly inhibit RVLM presympathetic neurons.…”

Gastric leptin: a novel role in cardiovascular regulation

“…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.…”