Vagal Efferent Fibers Research Articles

Role of vagal fibers and bombesin/gastrin-releasing peptide-neurons in distention-induced gastrin release in rats

In the rat the exact role of vagal fibers and the interaction between the extrinsic and intrinsic neural system in distention-induced gastrin release are still a matter of debate. Accordingly, the aim of the present study was to examine the contribution of afferent and efferent vagal fibers as well as intrinsic neurons on gastrin response to gastric distention. In anesthetized rats graded gastric distention by 5, 10 and 15 ml saline for 20 min caused a significant volume-dependent increase of plasma gastrin levels by 12±6 pg/ml (5 ml saline, n=8, P=0.05), 26±7 pg/ml (10 ml saline, n=10, P<0.05) and 37±7 pg/ml (15 ml saline, n=8, P<0.01), respectively. To examine the role of the extrinsic vagal innervation, gastrin response to distention was studied in anesthetized rats after bilateral truncal vagotomy ( n=9) or selective afferent vagotomy following pretreatment with capsaicin ( n=6). Stimulation of gastrin release by 10 ml distention in sham-operated control rats was reversed to an inhibition after truncal vagotomy (26±7 vs. −11±4 pg/ml; P<0.05) and capsaicin-treatment (37±18 vs. −34±11 pg/ml; P<0.05). A contribution of cholinergic mechanisms to this vagovagal-mediated stimulation of distention-induced gastrin release was excluded, since atropine (100 μg/kg/h; n=8) further augmented distention-stimulated gastrin release. Since bombesin/gastrin-releasing peptide (GRP)-neurons contribute to vagally stimulated gastrin secretion, we have examined gastrin response to distention in the presence of the specific bombesin-receptor antagonist d-Phe 6-BN(6-13)OMe (400 μg/kg/h; n=10). This bombesin-antagonist completely reduced distention-stimulated gastrin release in vivo. In contrast, distention of the isolated, extrinsically denervated stomach significantly decreased gastrin release by 13±5 pg/min (5 ml saline, n=8, P<0.05), 28±8 pg/min (10 ml saline, n=11, P<0.05) and 35±10 pg/min (15 ml saline, n=8, P<0.01), respectively, without changing the activity of bombesin/GRP-neurons. Distention-induced decrease of gastrin release was attenuated to 50 percent by atropine (10 −7 M; n=10) or tetrodotoxin (TTX) (10 −6 M; n=10), respectively. These data demonstrate, that in anesthetized rats distention-stimulated gastrin secretion depends on the activation of a vagovagal reflex and intrinsic bombesin/ GRP-neurons. In contrast distention of the isolated rat stomach inhibits gastrin release in part via intrinsic cholinergic pathways and other as yet unknown mechanisms.

New aspects of gastric adaptive relaxation, reflex after food intake for more food: involvement of capsaicin-sensitive sensory nerves and nitric oxide.

To accommodate the intake of food or liquid, gastric reservoir functions are important as the physiological reflex. There exist two major responses as a reservoir function of the stomach; adaptive and receptive relaxations. Adaptive relaxation is a reflex in which the fundus of the stomach dilates in response to small increases in intragastric pressure when food enters the stomach. Receptive relaxation is a reflex in which the gastric fundus dilates when food passes down the pharynx and the esophagus. The mechanisms of these two types of functional responses are to some extent different, although a nitric oxide (NO) dependent non adrenergic, non cholinergic neural pathway is involved in the both relaxation reflexes. Adaptive relaxation is an intragastric pressure induced reflex. Stretch of the gastric wall activates the mechanoreceptors in gastric mucosa (Mu), which generate impulses carried by the capsaicin-sensitive afferent sensory neuron. The sensory neuron can synapse on the inhibitory efferent neuron directly or activate it via interneurons of the myenteric plexus. This leads to the release of NO from the nitroxergic efferent neuron, which causes relaxation of circular muscle and hence of the fundus. Alternatively, an axon reflex causes the NO release from the sensory neuron, resulting in hexamethonium resistant gastric relaxation. Receptive relaxation is mediated by vagal motor fibers. In contrast with the pressure-induced adaptive relaxation, ganglionic nicotinic transmission is essential in the vagally induced relaxation. VIP and CGRP are important neurotransmitters of the inhibitory sensory neuron, which, however, may not mediate both adaptive and receptive relaxations. Disorders of these reservoir functions result in symptoms of early satiety and anorexia, which are the major symptoms of patients with functional dyspepsia.

Interaction between parasympathetic and sympathetic nerves in prevertebral ganglia: morphological evidence for vagal efferent innervation of ganglion cells in the rat.

Vagal efferent preganglionic neurons were anterogradely labeled by injecting either DiI or DiA, fluorescent lipophilic carbocyanine dyes, into the dorsal motor nucleus of the vagus of the rat. All neurons of the peripheral nervous system (outside the blood-brain barrier) were then fluorescently counterstained in vivo by injecting Fluorogold (Fluorochrome, Inc., Englewood, CO) intraperitoneally. The upper abdominal prevertebral ganglia, including the numerous microganglia associated with the periarterial plexuses of the celiac and superior mesenteric arteries, were identified and dissected in formalin-fixed tissue under ultraviolet light and stereomicroscopic guidance. In 14 of 15 animals analyzed (93%), labeled vagal efferent fibers were found to penetrate into both the left and right celiac ganglia and the superior mesenteric ganglion, as well as into some of the associated microganglia. These projections formed varicose terminal-like structures, highly suggestive of synaptic contacts surrounding individual ganglion cells. In about half the animals, such vagal innervation was also seen in the left and right suprarenal ganglia. The specificity of vagal efferent labeling was confirmed by control experiments, which included injections in vagotomized animals and direct selective labeling of vagal afferents from the nodose ganglia. It is concluded that vagal efferent preganglionics innervate principal ganglion cells of prevertebral ganglia. These vagal contacts may either directly modulate the postganglionic outflow or else gate some or all of the potential modulatory inputs to these postganglionic neurons, thus allowing the vagal system to exert a more selective influence on sympathetic outflow. Finally, the use of laser scanning confocal microscopy and the in toto Fluorogold staining method for investigations of the peripheral nervous system are discussed.

Involvement of the vagus nerve, substance P and cholecystokinin in the regulation of intestinal blood flow

Intestinal blood flow was recorded in anesthetized rats and cats using laser-Doppler flowmetry (LDF). This new technique provides continuous and accurate measurements of the intestinal blood flow, without affecting the blood circulation. Electrical stimulation (1 ms, 5–30 V, 5–50 Hz) applied either afferent or efferent vagal fibres elicited changes in the intestinal blood flow consisting mainly of increases. Similar results were obtained upon applying chemical stimulation to intestinal sensory endings using cholecystokinin (CCK) or substance P (SP; 10–20 μg/kg intravenously given). Bilateral vagotomy and atropine treatment markedly reduced or suppressed these vascular effects. In addition, experiments in which the activation of gastrointestinal afferents were activated by applying electrical stimulation to the abdominal vagal nerves yielded similar results. Finally, these effects were reduced after selectively severing vagal afferents. It is concluded that intestinal blood changes may be triggered by activation of the sensory endings from the digestive organs through the vagal nerves.

Vagal esophagomotor nerve function and esophageal motor performance in dogs with congenital idiopathic megaesophagus

Abstract Objectives To examine the integrity of the vagal efferent innervation to the esophagus and to assess esophageal motor performance in dogs with congenital idiopathic megaesophagus. Design An acute experimental protocol performed in control dogs and dogs with naturally acquired congenital idiopathic megaesophagus under pentobarbitone anesthesia. Animals 4 dogs with congenital idiopathic megaesophagus and 16 control dogs. Procedure Esophageal motor nerve conduction studies were performed by recording evoked compound motor action potentials from the tunica muscularis of the distal thoracic portion of the esophagus in response to supramaximal stimulation of the cervical portion of the vagus nerve at cranial and caudal sites. Subsequently, esophageal motor performance was measured over a wide range of esophageal muscle lengths by recording intraesophageal pressure responses to supramaximal twitch and tetanic stimulation of the cervical portion of the vagus at varying, stepwise amounts of esophageal distention. Results In dogs with congenital idiopathic megaesophagus, no electrophysiologic evidence was found for segmental demyelination or axonal degeneration in cervical vagal motor fibers innervating striated muscle of the thoracic esophagus portion. Nor was spontaneous EMG activity, indicative of esophageal muscle denervation or a primary myopathy, observed. In contrast, esophageal motor performance, which was dependent on esophageal dimensions, was reduced in dogs with congenital idiopathic megaesophagus. Conclusions In dogs with congenital idiopathic megaesophagus, the vagal efferent innervation to the esophagus is likely to be normal, a primary esophageal myopathy is unlikely to be present, and the observed reduction in esophageal motor performance may arise as a secondary consequence of altered esophageal biomechanical properties rather than from a primary neuromuscular abnormality. (Am J Vet Res 1996;57:906–913)

Lymphocyte traffic changes induced by monolateral vagal denervation in mouse thymus and peripheral lymphoid organs

In this report we show that after monolateral vagal denervation (vagotomy), performed at the cervical level, a transient effect, lasting about 24 h, was produced on lymphocyte release from mouse thymus to peripheral lymphoid organs (spleen and lymph nodes). Labelling thymocytes in situ with fluorescein isothiocyanate (FITC) we note that the export of immature cells, CD4 +CD8 +, double positive (DP), and double negative, CD4 −CD8 − (DN), from the thymus was consistently increased 24 and 48 h after vagotomy. Double staining with anti-L3T4 (CD4) and anti-mouse CD8α showed that the number of DP and UN cells was significantly higher in both spleen and lymph nodes of vagotomized mice compared to controls (sham-operated), whereas the percentage of CD4 +CD8 − and CD8 +CD4 −, single positives (SP), was decreased. Considering thymic cellularity and apoptotic values, we exclude the non-specific effect of stress and suggest that this phenomenon could be in part due to a transient lack of the facilitating influence exerted by vagal efferent fibers on lymphocyte traffic at the cortico-medullary junction of the thymic gland, where mature cells, SP, leave the thymus to enter systemic circulation.

The gut-brain brain-gut axis in anorexia: Toward an understanding of food intake regulation

Our long-term objectives continue to be elucidation of the mechanisms that control spontaneous food intake (SFI), so that we may utilize this information in seeking ways to ameliorate abnormalities of SFI that occur in nutritionally ill humans. To this end, we have developed and used an Automated Computerized Rat Eater Meter (ACREM), which allows detailed determinations of food intake and feeding patterns under a wide variety of experimental conditions. Because food intake is the product of meal number and meal size, these indexes were studied in a variety of experimental situations: normal male Fischer rats, genetically obese Zucker rats, cancer-bearing rats, and an inflammatory bowel rat model. In each model, a reduction in food intake was accomplished; usually by a selective reduction in meal number and, occasionally, meal size; often in both. The independent regulation of meal number and meal size strongly suggests the existence of focal neuronal areas in the hypothalamic food regulatory areas of the brain, which independently control these feeding indexes. To these feeding pattern studies were added in vivo focal hypothalamic microdialysis to correlate changes in meal size and number with changes in the basic neurotransmitters, dopamine and serotonin. To further gain an understanding of anorexia and food intake regulation in these models as it relates to the brain and gut interaction, we used metabolic stimulants, anatomic ablation, and electrophysiological studies, cytokines, selective neurotransmitter agonists, and antagonists peripherally in the gut and centrally in the brain. An integrated view of the gut-brain brain-gut control of food intake has emerged as a working and testable model system. The system includes oronasal pregastric factors, which stimulate an increase in LHA-dopamine facilitating gastric compliance via efferent vagal fibers; postabsorptive factors, including nutrients and hepatoportal receptors via afferent vagal fibers that inhibit further LHA-dopamine, thereby regulating meal size. The same postabsorptive factors simultaneously decrease VMH-dopamine, thereby determining postprandial intermeal duration, because food intake is resumed when VMH-dopamine normalizes—thus regulating meal number. Changes in plasma amino acids, the precursors for neurotransmitters, also affect brain availability for neurotransmitters. This in particular applies to tryptophan, the precursor of serotonin in the VMH, which induces a decrease in meal number and cytokines, which facilitate activity of both dopamine and serotonin.

The gut-brain brain-gut axis in anorexia: toward an understanding of food intake regulation.

Our long-term objectives continue to be elucidation of the mechanisms that control spontaneous food intake (SFI), so that we may utilize this information in seeking ways to ameliorate abnormalities of SFI that occur in nutritionally ill humans. To this end, we have developed and used an Automated Computerized Rat Eater Meter (ACREM), which allows detailed determinations of food intake and feeding patterns under a wide variety of experimental conditions. Because food intake is the product of meal number and meal size, these indexes were studied in a variety of experimental situations: normal male Fischer rats, genetically obese Zucker rats, cancer-bearing rats, and an inflammatory bowel rat model. In each model, a reduction in food intake was accomplished; usually by a selective reduction in meal number and, occasionally, meal size; often in both. The independent regulation of meal number and meal size strongly suggests the existence of focal neuronal areas in the hypothalamic food regulatory areas of the brain, which independently control these feeding indexes. To these feeding pattern studies were added in vivo focal hypothalamic microdialysis to correlate changes in meal size and number with changes in the basic neurotransmitters, dopamine and serotonin. To further gain an understanding of anorexia and food intake regulation in these models as it relates to the brain and gut interaction, we used metabolic stimulants, anatomic ablation, and electrophysiological studies, cytokines, selective neurotransmitter agonists, and antagonists peripherally in the gut and centrally in the brain. An integrated view of the gut-brain brain-gut control of food intake has emerged as a working and testable model system. The system includes oronasal pregastric factors, which stimulate an increase in LHA-dopamine facilitating gastric compliance via efferent vagal fibers; postabsorptive factors, including nutrients and hepatoportal receptors via afferent vagal fibers that inhibit further LHA-dopamine, thereby regulating meal size. The same postabsorptive factors simultaneously decrease VMH-dopamine, thereby determining postprandial intermeal duration, because food intake is resumed when VMH-dopamine normalizes--thus regulating meal number. Changes in plasma amino acids, the precursors for neurotransmitters, also affect brain availability for neurotransmitters. This in particular applies to tryptophan, the precursor of serotonin in the VMH, which induces a decrease in meal number and cytokines, which facilitate activity of both dopamine and serotonin.

Neural regulation of coronary vascular resistance: role of nitric oxide in reflex cholinergic coronary vasodilation in normal and pathophysiologic states.

A number of reflexes participate in the control of coronary vascular resistance through activation of the sympathetic or parasympathetic nervous system. Classically, activation of vagal efferent fibers to the heart results in vasodilation due to the release of acetylcholine and activation of muscarinic receptors. Recently, we have found that activation of a number of reflexes in conscious dogs, the Bezold-Jarisch reflex and the carotid chemoreflex in particular, results in cholinergic coronary vasodilation which is blocked by an inhibitor of nitric oxide synthesis, nitro-L-arginine. After the development of pacing-induced heart failure, the cholinergic dilation subsequent to activation of the Bezold-Jarisch or carotid chemoreflex is essentially abolished, since coronary blood vessels no longer produce nitric oxide. In contrast, after brief exercise training, there is a potentiation of Bezold-Jarisch reflex-induced coronary vasodilation since exercise upregulates nitric oxide production by coronary blood vessels. Since the Bezold-Jarisch reflex may be important as a compensatory mechanism during acute myocardial infarction, and the carotid chemoreflex is the acute mechanisms responsible for ameliorating systemic hypoxemia, the role of nitric oxide in reflex cholinergic coronary vasodilation may be essential in the compensatory vascular adjustments evoked by these and other reflexes.

The effect of interleukin-1β on the efferent activity of the vagus nerve to the thymus

The effects of intravenous (i.v.) administration of recombinant human interleukin-1β (rhIL-1β) and human interleukin-1β-fraction (hfrIL-1β) on the activity of vagal efferent fibers innervating the thymus were observed in urethane-anesthetized rats. An i.v. injection of 10 ng rhIL-1β or hfrIL-1β caused a similar degree of increase in the efferent activity, which lasted longer than 2 h. The least effective dose was 1 ng and dose-dependent responses were observed after i.v. injection of rhIL-1β at doses of 1 ng, 10 ng and 100 ng. The IL-1β-induced activation of efferent activity of the vagal branch to the thymus implicates their involvement in the neural modulation of the thymic function.

Orienting in a defensive world: mammalian modifications of our evolutionary heritage. A Polyvagal Theory.

The vagus, the 10th cranial nerve, contains pathways that contribute to the regulation of the internal viscera, including the heart. Vagal efferent fibers do not originate in a common brainstem structure. The Polyvagal Theory is introduced to explain the different functions of the two primary medullary source nuclei of the vagus: the nucleus ambiguus (NA) and the dorsal motor nucleus (DMNX). Although vagal pathways from both nuclei terminate on the sinoatrial node, it is argued that the fibers originating in NA are uniquely responsible for respiratory sinus arrhythmia (RSA). Divergent shifts in RSA and heart rate are explained by independent actions of DMNX and NA. The theory emphasizes a phylogenetic perspective and speculates that mammalian, but not reptilian, brainstem organization is characterized by a ventral vagal complex (including NA) related to processes associated with attention, motion, emotion, and communication. Various clinical disorders, such as sudden infant death syndrome and asthma, may be related to the competition between DMNX and NA.

Gastro-oesophageal afferent and serotonergic inputs to vagal efferent neurones

Peripheral 5-HT 3 receptor mechanisms are involved in activation of gastrointestinal (GI) mucosal vagal afferent fibres. 5-HT 3 receptor mechanisms in the central nervous system (CNS) may be involved in behavioural and reflex motility responses. This study investigates the processing of different sensory inputs in the CNS and the involvement of 5-HT 3 receptors at these different levels. In Urethane (1.5 g/kg, i.p.) anaesthetized, splanchnectomized ferrets, the jugular vein was cannulated for intravenous (i.v.) drug injection, and the cocliac axis for intraarterial (i.a.) injection close to the upper GI tract. The carotid artery was intubated with a T-cannula for CNS-directed intracarotid (i.e.) injections. An intragastric cannula was used for fluid distension (40–50 ml), and an oesophageal catheter for balloon distension (2 ml). Efferent fibres were dissected from the right cervical vagus for single-unit recording. Nineteen single vagal efferent fibres were selected, with low frequency resting discharge (2.5 ± 0.3 impulses/s), but no respiratory or cardiovascular phasic input. All responded rapidly (< 2.5 s) to gastric distension (532 ± 230% change in firing rate) and oesophageal distension (300 ± 170%). Gastric distension caused excitation in 14 fibres, inhibition in 4 fibres, and a biphasic response in 1. Oesophageal distension excited 16 and inhibited 3. Discharge was also influenced by i.a. injection of 5-HT or the 5-HT 3 receptor agonist 2-methyl 5-HT (10–100 μg) in all fibres tested. These responses consisted of rapid (< 2.5 s) and powerful changes in firing rate, with excitation, inhibition or biphasic responses. 65% of responses to i.e. or i.v. injection were opposite in direction to those after close i.a. injection, indicating the activation of a different population of receptors. No differences were seen between effects of i.e. and i.v. injections. The 5-HT 3 receptor antagonist granisetron (100 μg/kg, i.v.) blocked or reduced efferent responses to 5-HT receptor agonists, whereas responses to gastric and oesophageal distension were unchanged. Thus there is extensive convergence of inputs from gastric and oesophageal mechanoreceptors onto vagal motorneurones. These central effects of mechanical stimuli do not involve 5-HT 3 receptor mechanisms. Other 5-HT 3 receptor inputs are evident, probably peripherally from G1 mucosal afferent fibres and from within the CNS.

Efferent sympathetic and vagal innervation of the canine right ventricle.

The functional pathways of efferent sympathetic and vagal innervation to the right ventricle (RV) might be important in a variety of disease states that involve the RV wall. The purpose of this study was to investigate those pathways. We determined the effects of phenol and endocardial radiofrequency ablation applied to the RV anterolateral wall and outflow tract on effective refractory period (EPR) shortening during bilateral ansae subclaviae stimulation and ERP lengthening during bilateral vagal stimulation. We found that efferent sympathetic axons to the RV are located in the superficial subepicardium and that lateral sites receive sympathetic innervation predominantly from the lateral margin of the RV near the AV groove. Medial sites close to the left anterior descending coronary artery (LAD) receive sympathetic innervation from both the right lateral atrioventricular (AV) groove and regions near the LAD. At the RV outflow tract, some sympathetic fibers are located intramurally. Efferent vagal fibers are located at the RV surface within 10 mm of the right lateral AV groove; they penetrate intramurally and reach to the medial sites of the RV anterior wall. Other vagal fibers originate near the LAD and are intramural. Vagal fibers to the RV outflow tract are located intramurally either from the lateral side (close to the right coronary artery) or medial side (close to the LAD). Efferent vagal and sympathetic innervation of the right ventricle resembles that of the left ventricle. A major difference is that efferent sympathetic fibers to the right ventricular outflow tract are located not only in the subepicardium but in the subendocardium as well.

Intestinal distension alters vagal efferent activity and small intestinal transport in vivo

We investigated whether intestinal distension altered net water absorption by an adjacent noncontiguous segment of intestine and the mechanism for this effect. Influx and efflux catheters were placed in two intestinal loops, after which the bowel was transected between the loops. During perfusion with Ringers-HCO3-, the proximal loop efflux catheter was elevated 5, 10, or 15 cm above the plane of the rat. Net water absorption was measured in the nondistended caudal (control) loop. Elevation of the proximal loop efflux catheter caused distension and increased intraluminal pressure in this loop but did not alter the circumference or intraluminal pressure of the caudal loop. Distension increased net water absorption by the caudal loop if the vagi were intact and the splanchnic nerves transected. Afferent vagotomy prevented the distension effect. Using the intracellular recording technique, we were able to show that the increase in absorption resulted from a reduction in the activity of vagal neurons innervating the gastrointestinal tract. Intestinal distension reduced the neural activity of 24 of 26 vagal efferent neurons. Our results demonstrate that after splanchnectomy intestinal distension activates a neural circuit that includes afferent and efferent vagal fibers, resulting in increased water absorption.

Characterization of vagal innervation to the rat celiac, suprarenal and mesenteric ganglia

In order to shed light on the controversial issue of vagal innervation of the solar plexus ganglia, vagal efferent preganglionic fibers were anterogradely labeled by injecting the fluorescent carbocyanine dye Dil into the dorsal motor nucleus (dmnX). Additionally, Fluorogold was used to label the ganglia in toto, providing a counterstain and the possibility of UV light-guided dissection of the various ganglia. Using optical sectioning of whole mounted intact ganglia by means of laser scanning confocal microscopy, a considerable number of Dil-labeled vagal terminal-like structures were found in the major ganglia (celiac, superior mesenteric and suprarenal). Additionally, vagal efferent terminals were regularly found in microganglia associated with the periarterial plexuses of the celiac and superior mesenteric arteries, and in a few cases in small ganglia of the intermesenteric and renal plexuses. By using animals with prior selective vagal branch vagotomies, leaving only one (or a pair) of the three major abdominal divisions intact, it was concluded that the two celiac branches contribute the bulk of this vagal innervation, with the two gastric and the unpaired hepatic branch providing a small contribution mostly limited to the celiac ganglia. From control experiments, which involved Dil injections (1) into the dmnX in animals whose visceral afferents had been previously destroyed by capsaicin; (2) into the nodose ganglia, in order to anterogradely label vagal afferents; and (3) into the cervical vagus nerve as a control for uptake by fibers of passage, it was concluded that the identified terminal-like structures were vagal efferents and not inadvertently labeled afferents. We suggest that these vagal terminals have to be regarded either as ectopic parasympathetic junctions, or as part of a vagal mechanism for gating of sympathetic ganglionic transmission. Functionally, the parasympathetic innervation of the solar plexus may provide not only the classic vagal influence on gastrointestinal targets, but also vagal control of the adrenal glands and possibly other abdominal organs that have not been traditionally regarded as vagal targets.

Light microscopic localization of angiotensin II binding sites in canine medulla using high resolution autoradiography

Angiotensin II (Ang II) produces dose-related, site-specific cardiovascular effects in the canine and rat dorsal medulla. Our previous studies suggested that Ang II binding sites are associated with presynaptic vagal afferent fibers in the nucleus tractus solitarii (nTS) and vagal efferent neurons in the dorsal motor nucleus of the vagus (dmnX). High resolution autoradiography now establishes the relationship of putative Ang II receptors to the cytoarchitecture of these nuclei. Sections of the canine medulla oblongata were processed for film or emulsion autoradiography with 0.3–1 n M 125I-Ang II. Quantitative densitometry of films before and after processing sections for emulsion coating confirmed no selective alteration in labeling. In emulsion coated sections, dense labeling was seen over the majority of the large perikarya and surrounding neuropil in the ventral dmnX. Bands of label overlaid vagal efferent fibers coursing ventrolaterally to exit the medulla. In the nTS, Ang II binding was restricted to regions with heavy vagal afferent innervation. In the dorsal nTS, label was distributed over both cell bodies and neuropil, with highest density capping the solitary tract. In the medial nTS, label was concentrated over perikarya, with scattered grains over the intervening neuropil. The discrete subnuclear association of Ang II binding sites in the dorsal medulla with vagal cells and fibers documents that Ang II receptors are present on both afferent vagal fibers and intrinsic medullary neurons, and reveals an anatomical substrate for the autonomie effects of Ang II in this region.

An anterograde tracing study of the vagal innervation of rat liver, portal vein and biliary system.

In order to investigate the distribution and structure of the vagal liver innervation, abdominal vagal afferents and efferents were selectively labeled by injecting WGA-HRP or Dil into the nodose ganglia, and DiA into the dorsal motor nucleus, respectively. Vagal afferent fibers produced characteristic terminal-like structures at three locations in the liver hilus: 1. Fine varicose endings preferentially surrounding, but not entering, the numerous peribiliary glands in the larger intra and extrahepatic bile ducts 2. Large, cup-shaped terminals in almost all paraganglia 3. Fine varicose endings in the portal vein adventitia. No fibers and terminals were found in the hepatic parenchyma. While about two thirds of the vagal afferent fibers that originate in the left nodose ganglion, and are contained in the hepatic branch, bypass the liver hilus area on their way to the gastroduodenal artery, a significant number (approx. 10% of the total) of vagal afferents that do innervate the area, originates from the right nodose ganglion, and projects to the periarterial plexus of the common hepatic artery and liver pedicle most likely through the dorsal celiac branch. Varicose vagal efferent fibers were present within the fascicles of the vagal hepatic branch and fine terminal-like structures in a small fraction of the paraganglia. No efferents were found to terminate in the hepatic parenchyma or on the few neurons embedded in nerves or paraganglia. In contrast to the paucity of vagal terminals in the hepatic parenchyma, an abundance of vagal efferent and afferent fibers and terminals with distinctive distribution patterns and structural characteristics was present in esophagus and gastrointestinal tract.(ABSTRACT TRUNCATED AT 250 WORDS)

Vagal afferent innervation of the rat fundic stomach: morphological characterization of the gastric tension receptor.

Although the gastric tension receptor has been characterized behaviorally and electrophysiologically quite well, its location and structure remains elusive. Therefore, the vagal afferents to the rat fundus (forestomach or nonglandular stomach) were anterogradely labeled in vivo with injections of the carbocyanine dye Dil into the nodose ganglia, and the nerves and ganglia of the enteric nervous system were labeled in toto with intraperitoneal Fluorogold injection. Dissected layers and cryostat cross sections of the fundic wall were mounted in glycerin and analyzed by means of conventional and laser scanning confocal microscopy. Particularly in the longitudinal, and to a lesser extent in the circular, smooth muscle layers, Dil-labeled fibers and terminals were abundant. These processes, which originated from fibers coursing through the myenteric ganglia and connectives, entered either muscle coat and then ran parallel to the respective muscle fibers, often for several millimeters. They ran in close association with the Fluorogold-labeled network of interstitial cells of Cajal, upon which they appeared to form multiple spiny appositions or varicosities. In the myenteric plexus, two different types of afferent vagal structures were observed. Up to 300 highly arborizing endings forming dense accumulations of small puncta similar to the esophageal intraganglionic laminar endings (Rodrigo et al., '75 Acta Anat. 92:79-100) were found in the fundic wall ipsilateral to the injected nodose ganglion. They often covered small clusters of myenteric neurons or even single isolated ganglion cells (mean = 5.8 neurons) and tended to extend throughout the neuropil of the ganglia. In a second pattern, fine varicose fibers with less profuse arborizations innervated mainly the central regions of myenteric ganglia. Camera lucida analyses established that single vagal afferent fibers had separate collaterals in both a smooth muscle layer and the myenteric ganglia. Finally, Dil-labeled afferent vagal fibers were also found in the submucosa and mucosa. Control experiments in rats with supranodose vagotomy as well as rats with Dil injections directly in the distal cervical vagus ruled out the possibility of colabeling of afferent fibers of passage. In triple labeling experiments, in conjunction with Dil labeling of afferents and Fluorogold labeling of enteric neurons, the carbocyanine dye DiA was injected into the dorsal motor nucleus of the vagus to anterogradely label the efferent vagal fibers and terminals. The different distributions and morphological characteristics of the vagal afferents and efferents could be simultaneously compared. In some instances the same myenteric ganglion was apparently innervated by an afferent laminar ending and an efferent terminal.(ABSTRACT TRUNCATED AT 400 WORDS)

Single cardiac vagal fiber activity, acute myocardial ischemia, and risk for sudden death.

Experimental and clinical evidence indicates that high risk for sudden death is significantly correlated with post-myocardial infarction depression in two "markers" of vagal activity, heart rate variability and baroreflex sensitivity. The present experiments were designed to answer some of the questions generated by those findings. In 33 anesthetized cats, the neural activity of single cardiac vagal efferent fibers was recorded in control conditions and after injection of phenylephrine (n = 33), before and during a 1-hour coronary artery occlusion (CAO) (n = 17), and before and after removal of the left stellate ganglion (n = 16). In the first minute after CAO, vagal activity increased by 35% from 1.66 +/- 0.37 to 2.57 +/- 0.62 impulses/sec (p less than 0.01); despite a slight decline, it remained for the entire CAO above the control values, to which it returned after CAO release. Of 17 cats, ventricular fibrillation occurred in nine (susceptible) and eight survived (resistant). Resistant and susceptible cats had different reflex vagal responses to CAO. Whereas the resistant cats had a 48% (p less than 0.01) increase by the second minute of CAO, susceptible cats had no change (-18%, p = NS) in vagal activity. These differences were independent of blood pressure changes. The increase in vagal efferent activity in response to the blood pressure rise induced by phenylephrine (baroreceptive reflex) was more marked in the resistant cats compared with the susceptible cats (+246 +/- 66% versus +80 +/- 14%, p less than 0.025). Just before the injection of phenylephrine, vagal activity was not different between resistant and susceptible cats (1.58 +/- 0.35 versus 1.48 +/- 0.30 impulses/sec, p = NS). In 16 cats, left stellectomy increased cardiac vagal efferent activity by 75% (p less than 0.01), and the reflex vagal activation secondary to phenylephrine was further enhanced (from 2.2 +/- 0.4 to 4.7 +/- 0.7 impulses/sec, p less than 0.001). These data demonstrate that 1) cardiac vagal efferent activity increases in response to acute myocardial ischemia--much more so among the animals destined to survive, 2) before CAO, susceptible and resistant animals can be identified by the vagal response to blood pressure increase (assessed clinically by baroreflex sensitivity) and not by tonic vagal activity (assessed clinically by heart rate variability), and 3) the findings with left stellectomy support the hypothesis that vagal activity decreases after myocardial infarction because of an increase, secondary to abnormal stretch of the cardiac mechanoreceptors, in cardiac sympathetic afferent traffic, which exerts a tonic restraint on vagal outflow.

Cardiac Pain, Sympathetic Afferents, and Life‐Threatening Arrhythmias

Cardiac Pain, Sympathetic Afferents, and Life‐Threatening Arrhythmias. Myocardial ischemia activates receptors of sympathetic and vagal afferent fibers. Although both afferent pathways are excited, this article primarily focuses on the sympathetic pathways. Increased sympathetic afferent activity to cells of the spinal cord can lead to cardiac pain and reflex sympathetic hyperactivity that can be quite arrhythmogenic. Complicating factors that affect the relationship arises from activation of vagal afferent fibers. Sympathetic afferent fibers in the ventricle appear to be composed of mechanosensitive and chemosensitive receptors. Sympathetic afferent fibers excite cells of origin of the spinothalamic tract, the classical pain pathway that transmits information about noxious somatic and visceral episodes to areas of the brain involved with pain perception. Activation of selected brainstem nuclei, the vagus, and the dorsal columns can suppress afferent information from the heart that excites spinothalamic tract cells. Excitation of sympathetic afferent fibers initiates a series of cardiovascular reflexes, some of which may affect cardiac electrical stability significantly. Increased arrhythmogenesis can be reduced when C8‐T5 dorsal roots are transected. Stimulation of cardiac nerves that involve the left stellate ganglion can produce life‐threatening arrhythmias, particularly if combined with myocardial ischemia or infarction. Through reflex mechanisms, activation of sympathetic afferent fibers can suppress activity of vagal efferent fibers. If prevention of cardiac pain through reduced firing or inhibition of cells in the spinothalamic tract reduces afferent sympathetic activity that occurs during acute myocardial ischemia, it would be logical to surmise that another significant benefit would follow, namely reduced risk for malignant arrhythmias.