Neuropeptides as central integrators of autonomic nerve activity: effects of TRH, SRIF, VIP and bombesin on gastric and adrenal nerves

The nerve activity of the gastric ramus of the splanchnic (sympathetic) nerve, gastric ramus of the vagus, adrenal ramus of the splanchnic nerve and the superior laryngeal nerve (laryngeal ramus of vagus) were assessed before and after i.c.v. injection of neuropeptides in the rat. TRH stimulated the vagal branch but attenuated the sympathetic outflow to the stomach. In contrast, the sympathetic outflow to the adrenal was enhanced by TRH. SRIF suppressed the activity of all the nerves studied. VIP did not affect the sympathetic outflow to the stomach while suppressing the gastric branch of the vagus. The adrenal sympathetic branch as well as the superior laryngeal nerve was stimulated by VIP. Bombesin suppressed both vagal and sympathetic outflow to the stomach but markedly stimulated the laryngeal branch of the vagus. The adrenal sympathetic nerve was either stimulated or attenuated slightly by bombesin. These results indicate that centrally administered neuropeptides produce reactions specific for each nerve.     

Galanin-like immunoreactivity in extrinsic and intrinsic nerves to the gut of the Atlantic cod,Gadus morhua,and the effect of galanin on the smooth muscle of the gut

The presence of galanin-like immunoreactivity in nerves to the stomach of the Atlantic cod has been investigated by immunohistochemistry. The distribution of ganglion cells showing galanin-like immunoreactivity was compared with the total distribution in nerves and ganglia. Projection studies were made to determine the origin of the galanin neurons. The effect of galanin was studied in smooth muscle strip preparations of the gut wall and arteries. Galanin-like immunoreactive ganglion cells frequently occurred along the vagal branches to the stomach. Most of them projected cranially. Immunoreactive nerve fibres were present in all layers of the gut and around arterial branches on the surface of the stomach. Ligations of the vagus and splanchnic nerves produced accumulations of immunoreactive material on both sides of the ligature. Galanin produced weak contractile effects unaffected by tetrodotoxin on the gut wall and on gut arteries. It is concluded that a population of the ganglion cells along the vagus nerve in the Atlantic cod contains a galanin-like peptide. Some of these cells may be parts of autonomic parasympathetic pathways innervating the gut of the Atlantic cod, having direct excitatory effects on the smooth muscles of the gut wall and gut arteries.     

Smooth-muscle-specific expression of neurotrophin-3 in mouse embryonic and neonatal gastrointestinal tract

Vagal gastrointestinal (GI) afferents are essential for the regulation of eating, body weight, and digestion. However, their functional organization and the way that this develops are poorly understood. Neurotrophin-3 (NT-3) is crucial for the survival of vagal sensory neurons and is expressed in the developing GI tract, possibly contributing to their survival and to other aspects of vagal afferent development. The identification of the functions of this peripheral NT-3 thus requires a detailed understanding of the localization and timing of its expression in the developing GI tract. We have studied embryos and neonates expressing the lacZ reporter gene from the NT-3 locus and found that NT-3 is expressed predominantly in the smooth muscle of the outer GI wall of the stomach, intestines, and associated blood vessels and in the stomach lamina propria and esophageal epithelium. NT-3 expression has been detected in the mesenchyme of the GI wall by embryonic day 12.5 (E12.5) and becomes restricted to smooth muscle and lamina propria by E15.5, whereas its expression in blood vessels and esophageal epithelium is first observed at E15.5. Expression in most tissues is maintained at least until postnatal day 4. The lack of colocalization of β-galactosidase and markers for myenteric ganglion cell types suggests that NT-3 is not expressed in these ganglia. Therefore, NT-3 expression in the GI tract is largely restricted to smooth muscle at ages when vagal axons grow into the GI tract, and when vagal mechanoreceptors form in smooth muscle, consistent with its role in these processes and in vagal sensory neuron survival.     

Selective ablation of spinal afferent neurons containing CGRP attenuates gastric hyperemic response to acid.

The gastric mucosa, in particular submucosal blood vessels, are innervated by afferent neurons containing neuropeptides such as calcitonin gene-related peptide. Stimulation of sensory neurons innervating the gastric mucosa increases submucosal blood flow. Since sensory neurons supplying the stomach are of dual origin from nodose and dorsal root ganglia, we examined the effect of selective ablation of either the vagal or spinal sensory innervation to the upper gastrointestinal tract on the increase in gastric mucosal blood flow in response to acid back diffusion into the gastric mucosa. Perineural application of capsaicin to the celiac/superior mesenteric ganglia, but not to the vagus nerves, significantly inhibited by 53% the hyperemic response to acid back diffusion. Tissue levels of immunoreactive calcitonin gene-related peptide in the gastric corpus were significantly reduced (by 73%) by periceliac capsaicin treatment, but unaffected by perivagal capsaicin treatment. These data suggest that spinal capsaicin-sensitive afferents containing calcitonin gene-related peptide immunoreactivity are involved in mediating increases in gastric mucosal blood flow. This increase in gastric mucosal blood flow mediated by sensory neurons may act as a protective mechanism against mucosal injury, similar to responses seen in other tissues such as skin.     

Transient catecholaminergic (TC) cells in the vagus nerves and bowel of fetal mice: relationship to the development of enteric neurons

Catecholaminergic cells are transiently present during development of the fetal murine bowel. These transient catecholaminergic (TC) cells appear at Day E10, but by Day E13 can no longer be detected. In order to evaluate the hypothesis that these cells are the precursors of enteric neurons, we investigated the possibilities that TC cells coexpress neuronal and catecholaminergic markers, that they can be found along the presumed path followed by crest-derived cells migrating to the gut, and that they are proliferating. TC cells were identified immunocytochemically using polyclonal or monoclonal antibodies to tyrosine hydroxylase (TH). At Day E9.5, TH-immunoreactive cells were observed to be present along the wall of the primordial esophagus in lines that extended from the developing nodose ganglia down to the boundary of the stomach. At Day E9.5, TC cells were absent from the remaining foregut. These lines of esophageal TH-immunoreactive cells became continuous with similar cells in the wall of the stomach and duodenum on Day E10. Coincident expression of neurofilament immunoreactivity was seen in all of the esophageal TH-immunoreactive cells present at Day E9.5, as well as in the entire set of esophageal and lower enteric TH-immunoreactive cells present at Day E10 (or later); moreover, at Days E9.5 and E10, all of the neurofilament-immunoreactive cells in the esophagus, stomach, or duodenum were also TH-immunoreactive. In contrast, neurofilament immunoreactivity was not expressed by the endodermally derived pancreatic duct and islet cells, which were also TH-immunoreactive; nor could expression of neurofilament immunoreactivity be detected in the TH-immunoreactive cells of the nodose ganglia. It was not until Day E11 that neurofilament-immunoreactive cells, which did not coexpress TH immunoreactivity (the definitive phenotype of enteric neurons) began to appear in the gut. Vagal axons reached as far distally as the nodose ganglion on Day E9.5, the esophagogastric junction on Day E10, and did not enter the stomach until Day E11. When the vagus nerves reached their level, the TH-immunoreactive cells in the wall of the esophagus came to lie among the nerve fibers. TH-immunoreactive cells are thus present on the pathway ultimately followed by the vagus nerves, but they develop before vagal fibers reach their level. The vagal TH-immunoreactive cells, therefore, are probably not initially migrating on vagal fibers, but appear instead to be overtaken by the descending vagus nerves.(ABSTRACT TRUNCATED AT 400 WORDS)     

Autonomic nervous control of gastric somatostatin secretion from the perfused rat stomach

The effect of parasympathetic and sympathetic nerve stimulation on the secretion of gastric somatostatin and gastrin has been studied in an isolated perfused rat stomach preparation. Stimulation of the vagus nerve inhibited somatostatin secretion and increased gastrin release. Splanchnic nerve stimulation increased somatostatin release during simultaneous atropine perfusion, but not in its absence, whereas gastrin secretion was unchanged. The secretory activity of the gastric D-cell was therefore reciprocally influenced by the sympathetic and parasympathetic nerves but sympathetic stimulation was only effective during muscarinic blockade.     

Phenotypic characterization of gastric sensory neurons in mice

Recent studies suggest that the capsaicin receptor [transient receptor potential vanilloid (TRPV)1] may play a role in visceral mechanosensation. To address the potential role of TRPV1 in vagal sensory neurons, we developed a new in vitro technique allowing us to determine TRPV1 expression directly in physiologically characterized gastric sensory neurons. Stomach, esophagus, and intact vagus nerve up to the central terminations were carefully dissected and placed in a perfusion chamber. Intracellular recordings were made from the soma of nodose neurons during mechanical stimulation of the stomach. Physiologically characterized neurons were labeled iontophoretically with neurobiotin and processed for immunohistochemical experiments. As shown by action potential responses triggered by stimulation of the upper thoracic vagus with a suction electrode, essentially all abdominal vagal afferents in mice conduct in the C-fiber range. Mechanosensitive gastric afferents encode stimulus intensities over a wide range without apparent saturation when punctate stimuli are used. Nine of 37 mechanosensitive vagal afferents expressed TRPV1 immunoreactivity, with 8 of the TRPV1-positive cells responding to stretch. A small number of mechanosensitive gastric vagal afferents express neurofilament heavy chains and did not respond to stretch. By maintaining the structural and functional integrity of vagal afferents up to the nodose ganglion, physiological and immunohistochemical properties of mechanosensory gastric sensory neurons can be studied in vitro. Using this novel technique, we identified TRPV1 immunoreactivity in only one-fourth of gastric mechanosensitive neurons, arguing against a major role of this ion channel in sensation of mechanical stimuli under physiological conditions.     

Neurons in the rat lateral hypothalamic area integrate information from the gastric vagal nerves and the cerebellar interpositus nucleus

Previous investigations have demonstrated that the neuronal activity in the lateral hypothalamic area (LHA) is respectively modulated by afferent inputs from the gastric vagal nerves innervating the upper gastrointestinal tract, as well as the cerebellar interpositus nucleus (IN). The aim of this study was to examine whether the gastric vagal and cerebellar IN inputs converge onto single LHA neurons in rats, especially those sensitive to glycemia. Of the 114 LHA neurons recorded, 60 (52.6%) and 51 (44.7%) responded to gastric vagal and cerebellar IN stimulation, respectively. Of the 60 LHA neurons responsive to gastric vagal stimulation, 30 also responded to the cerebellar IN stimulus, indicating a convergence of gastric vagal and cerebellar inputs onto single hypothalamic cells. When the gastric vagal nerves and cerebellar IN were stimulated simultaneously, a summation of the responses was observed in all 6 neurons tested. Moreover, of 24 neurons that responded to both the gastric vagal and cerebellar IN stimuli, 15 (62.5%) were identified as glycemia-sensitive. These results demonstrate that the visceral information transmitted by the gastric vagal nerves and the somatic information forwarded by the cerebellar IN converge onto single LHA neurons, especially those sensitive to glycemia. The findings also suggest that integration of somatic-visceral responses related to short-term feeding regulation may take place in the LHA.     

Catecholamines abolish vagal but not acetylcholine tone in the intact cat trachea

To obtain evidence in the airways that catecholamines inhibit cholinergic neurotransmission, we recorded transverse tension in the posterior wall of an upper tracheal segment in anesthetized cats and compared the inhibitory effect of stimulating cervical sympathetic nerves when segment contraction was evoked by endogenous acetylcholine (vagal tone) with the effect when contraction was evoked by exogenous acetylcholine applied directly to the mucosal surface of the tracheal segment (ACh tone). We found that sympathetic stimulation abolished all contraction evoked by vagal tone but reduced ACh tone by only one-half. In a second group of cats we compared the inhibitory effects of sympathetic stimulation and intravenous isoproterenol during vagal and ACh tone and also during tone evoked by exogenous 5-hydroxytryptamine (5-HT tone). Sympathetic stimulation or isoproterenol injection abolished all vagal and 5-HT tone but again reduced ACh tone by only one-half. Our results suggest that catecholamines released from sympathetic nerves or injected into the circulation completely inhibit vagal tone. This inhibition may be partially responsible for inducing relaxation in airway smooth muscle.     

Immunolocalization of the HNK-1 epitope in the autonomic innervation to the liver and upper digestive tract of the developing rat embryo

The immunohistochemical analysis of the HNK-1 epitope presence in the liver and upper digestive tract nerves was carried out in 12- to 18-day-old rat embryos embedded in acrylamide–agarose and observed with laser scanning confocal microscopy. The vagus and sympathetic trunk were intensely immunostained at all ages; branches of both structures were also HNK-1 positive, and ramified ventrocaudally following the course of the thoracic and abdominal aorta, caval vein, portal vein and ductus venosus. As early as day 12, some immunostained cells were seen in the mesentery that formed the enteric nervous system. Clearly immunostained HNK-1-immunoreactive fibres were detected innervating the digestive wall after day 14, forming both myenteric and submucosal plexuses. After day 16, the Glisson sheath showed streams of HNK-1-positive fibres coming from dorsal areas, lining the peritoneal surface of the diaphragm, invading the capsule, and ramifying superficially around the lobes of the liver. We saw no immunoreactive structures pervading the hepatic lobes at all ages studied, with the exception of occasional HNK-1-positive cells in the superficial parenchyma, which were visualized after 16 days of gestation. Our findings can help to understand the development of the gastrointestinal and liver innervation in the rat.     

Retroperitoneal paraganglia and the peripheral autonomic nervous system in the human fetus

By means of the AChE in toto staining method retroperitoneal paraganglia and the peripheral autonomic nervous system in human fetuses have been investigated. Many small retroperitoneal paraganglia are present near the sympathetic trunks close to the sympathetic trunk ganglia. In the thoracic region small paraganglia are present in the intercostal spaces. Small splanchnic nerves entering small paraganglia have been described. In the lower sacral region no paraganglia are present. The major splanchnic nerve arises at various levels from the sympathetic trunks as well as many smaller thoracic splanchnic nerves. Intermediate ganglia are present in the major splanchnic nerve, the smaller splanchnic nerves and the communicating rami. In the sympathetic trunks many ganglia are fused. In the human fetus there exists a large variability in number and diameter of the communicating rami. Interconnecting bundles of nerve fibers between the left and right sympathetic trunks are present at all levels, but most numerous at the sacral level.     

Neurofilament immunoreactivity and acetylcholinesterase activity in the developing sympathetic tissues of the rat

Summary In this study, the ontogenetic appearance of three neuronal markers, tyrosine hydroxylase (TH), neurofilament (NF) proteins and acetylcholinesterase (AChE), have been compared in the neural tube and derivatives of the neural crest with special consideration on developing rat sympathetic tissues. The tree markers appeared for the first time on embryonic day E 12.5. At this age, NF immunoreactivity was located in the cells on the ventro- and dorsolateral edges of the neural tube, i.e., in the regions where the cells had reached the postmitotic stage. In addition, on day E 12.5, NF-immunoreactive fibers were located in the dorsal and ventral roots and the spinal and sympathetic ganglia. This suggests rapid extension of neurites. In contrast to NF, AChE first appeared on day E 12.5 in cell somata of spinal and sympathetic ganglia ond only after that in axons. Thus, it can be considered as a marker of differentiating neuronal cell bodies. In the developing sympathoadrenal cells, TH is expressed before NF and AChE. However, the migrating TH immunoreactive sympathetic cells are constantly followed by NF immunoreactive fibers, suggesting that sympathetic tissues may receive innervation from preganglionic axons at the very beginning of their ontogeny. During the later development, all sympathetic tissues contain two major cell groups: 1) one with a moderate TH immunoreactivity, NF immunoreactivity and AChE activity and 2) the other with an intense TH immunoreactivity but lacking NF immunoreactivity or AChE activity. The former includes principal neurons, neuron-like cells of the paraganglia and noradrenaline cells of the adrenal medullae, and the latter includes ganglionic small intensely fluorescent (SIF) cells, paraganglionic cells and medullary adrenaline cells.     

Neurofilament immunoreactivity and acetylcholinesterase activity in the developing sympathetic tissues of the rat.

In this study, the ontogenetic appearance of three neuronal markers, tyrosine hydroxylase (TH), neurofilament (NF) proteins and acetylcholinesterase (AChE), have been compared in the neural tube and derivatives of the neural crest with special consideration on developing rat sympathetic tissues. The tree markers appeared for the first time on embryonic day E 12.5. At this age, NF immunoreactivity was located in the cells on the ventro- and dorsolateral edges of the neural tube, i.e., in the regions where the cells had reached the postmitotic stage. In addition, on day E 12.5, NF-immunoreactive fibers were located in the dorsal and ventral roots and the spinal and sympathetic ganglia. This suggests rapid extension of neurites. In contrast to NF, AChE first appeared on day E 12.5 in cell somata of spinal and sympathetic ganglia and only after that in axons. Thus, it can be considered as a marker of differentiating neuronal cell bodies. In the developing sympathoadrenal cells, TH is expressed before NF and AChE. However, the migrating TH immunoreactive sympathetic cells are constantly followed by NF immunoreactive fibers, suggesting that sympathetic tissues may receive innervation from preganglionic axons at the very beginning of their ontogeny. During the later development, all sympathetic tissues contain two major cell groups: 1) one with a moderate TH immunoreactivity, NF immunoreactivity and AChE activity and 2) the other with an intense TH immunoreactivity but lacking NF immunoreactivity or AChE activity. The former includes principal neurons, neuron-like cells of the paraganglia and noradrenaline cells of the adrenal medullae, and the latter includes ganglionic small intensely fluorescent (SIF) cells, paraganglionic cells and medullary adrenaline cells.     

Reconstruction of the Abdominal Vagus Nerve Using Sural Nerve Grafts in Canine Models

Background

Recently, vagus nerve preservation or reconstruction of vagus has received increasing attention. The present study aimed to investigate the feasibility of reconstructing the severed vagal trunk using an autologous sural nerve graft.

Methods

Ten adult Beagle dogs were randomly assigned to two groups of five, the nerve grafting group (TG) and the vagal resection group (VG). The gastric secretion and emptying functions in both groups were assessed using Hollander insulin and acetaminophen tests before surgery and three months after surgery. All dogs underwent laparotomy under general anesthesia. In TG group, latency and conduction velocity of the action potential in a vagal trunk were measured, and then nerves of 4 cm long were cut from the abdominal anterior and posterior vagal trunks. Two segments of autologous sural nerve were collected for performing end-to-end anastomoses with the cut ends of vagal trunk (8–0 nylon suture, 3 sutures for each anastomosis). Dogs in VG group only underwent partial resections of the anterior and posterior vagal trunks. Laparotomy was performed in dogs of TG group, and latency and conduction velocity of the action potential in their vagal trunks were measured. The grafted nerve segment was removed, and stained with anti-neurofilament protein and toluidine blue.

Results

Latency of the action potential in the vagal trunk was longer after surgery than before surgery in TG group, while the conduction velocity was lower after surgery. The gastric secretion and emptying functions were weaker after surgery in dogs of both groups, but in TG group they were significantly better than in VG group. Anti-neurofilament protein staining and toluidine blue staining showed there were nerve fibers crossing the anastomosis of the vagus and sural nerves in dogs of TG group.

Conclusion

Reconstruction of the vagus nerve using the sural nerve is technically feasible.     

尾核P物质对胃运动的抑制效应系通过黑质,迷走背核经迷走神经所介导

本工作观察损毁下丘脑外侧区,黑质,迷走背核及其传出神经对尾核微量注射Ｐ物质引起的胃肌电快波和胃运动抑制效应的影响。实验结果：该抑制效应不依赖于下丘脑外侧区的完整但可被损毁黑质,迷走背核或迷走上所消除。用利血平耗竭交感神经递质则不影响该效应。这些结果表明：尾核ＳＰ的抑胃效应系通过黑质、迷走背核经迷走神经所传出。     

Vanilloid receptor (VR1) expression in vagal afferent neurons innervating the gastrointestinal tract

The vanilloid receptor VR1 is a nonselective cation channel activated by capsaicin as well as increases in temperature and acidity, and can be viewed as molecular integrator of chemical and physical stimuli that elicit pain. The distribution of VR1 receptors in peripheral and central processes of rat primary vagal afferent neurons innervating the gastrointestinal tract was investigated by immunohistochemistry. Forty-two percent of neurons in the nodose ganglia retrogradely labeled from the stomach wall expressed low to moderate VR1 immunoreactivity (VR1-IR). VR1-IR was considerably lower in the nodose ganglia as compared to the jugular and dorsal root ganglia. In the vagus nerve, strongly VR1-IR fibers ran in separate fascicles that supplied mainly cervical and thoracic targets, leaving only weakly VR1-IR fibers in the subdiaphragmatic portion. Vagal afferent intraganglionic laminar endings (IGLEs) in the gastric and duodenal myenteric plexus did not express VR1-IR. Similarly, VR1-IR was contained in fibers running in perfect register with vagal afferents, but was not colocalized with horseradish peroxidase in the same varicosities of intramuscular arrays (IMAs) and vagal afferent fibers in the duodenal submucosa anterogradely labeled from the nodose ganglia. Only in the gastric mucosa did we find evidence for colocalization of VR1-IR in vagal afferent terminals. In contrast, many nerve fibers coursing through the myenteric and submucosal plexuses contained detectable VR1-IR, the majority of which colocalized calcitonin gene-related peptide immunoreactivity. In the dorsal medulla there was a dense plexus of VR1-IR varicose fibers in the commissural, dorsomedial and gelatinosus subnuclei of the medial NTS and the lateral aspects of the area postrema, which was substantially reduced, but not eliminated on the ipsilateral side after supranodose vagotomy. It is concluded that about half of the vagal afferents innervating the gastrointestinal tract express low levels of VR1-IR, but that presence in most of the peripheral terminal structures is below the immunohistochemical detection threshold.     

The intramural innervation of the rabbit upper urinary tract

The role of the autonomic innervation of the upper urinary tract for pyeloureteral motility is not completely understood. It is still debatable if the autonomic nervous system might play a modulating role on the ureteral peristalsis. The aim of this study was to investigate the distribution and regional variation of the intramural innervation using whole-mount preparations of the rabbit upper urinary tract. Whole-mount preparation was performed at upper urinary tracts of healthy rabbits. Immunohistochemistry was employed using Neurofilament (NF), Tyrosine Hydroxylase (TH), Choline Acetyltransferase (ChAT) and Substance P (SP) antibodies. NADPH-diaphorase and Acetylcholinesterase (AChE) histochemistry was carried out at the specimens. The stains were evaluated using brightfield, fluorescence and laser confocal microscopy. NF-, TH-, ChAT- and SP-immunoreactive (-IR) nerves formed distinct neuronal plexuses at the submucosal and muscle layers. Perivascular TH-, ChAT- and SP-IR fibres were demonstrated. AChE positive nerves were revealed in all layers, but only moderate NADPH-diaphorase positive innervation was found. Renal pelvis, upper and lower ureter showed enriched intrinsic innervation. Ganglia were found at the ureteropelvic border and the distal ureter. Whole-mount preparation technique revealed detailed informations about morphology and regional variation of the intramural innervation of the rabbit upper urinary tract.     

刺激迷走神经和酸化十二指肠对狗胰液分泌的相互影响

用5条制备有 Thomas 胰瘘和胃瘘的狗作慢性麻醉实验,观察刺激迷走神经和酸化十二指肠对胰液分泌的相互影响,结果如下:1.在酸化肠的情况下,刺激迷走神经所引起的胰蛋白质和碳酸氢盐的排出量显著增多,其效应超过单独刺激迷走神经和酸化肠所产生效应之和。2.在酸化肠引起胰分泌停止后的短时间内,再刺激迷走神经,胰液分泌的潜伏期缩短,蛋白质和碳酸氢盐排出量增多。3.阻断迷走冲动或注射阿托品后,酸化肠所引起胰液的分泌明显减少。4.用利多卡因麻痹肠粘膜后,酸化肠所引起胰液的分泌也明显降低。这些结果提示,在酸化十二指肠引起胰液分泌的机制中,有迷走神经和局部神经参与,迷走冲动和促胰液素及促胰酶素共同作用靶器官时,有相互加强作用,一旦迷走冲动被阻断,这两种激素的作用即明显降低。     

Vagal afferent activity and renal nerve release of dopamine

To investigate the involvement of vagal afferents in renal nerve release of catecholamines, we compared norepinephrine, dopamine, and epinephrine excretion from innervated and chronically denervated kidneys in the same rat. The difference between innervated and denervated kidney excretion rates was taken as a measure of neurotransmitter release from renal nerves. During saline expansion, norepinephrine excretion from the innervated kidney was not statistically greater than from denervated kidneys. Vagotomy increased norepinephrine release from renal nerves. Thus vagal afferents participated in the suppression of renal sympathetic nerve activity during saline expansion. No significant vagal control of dopamine release by renal nerves was detected under these conditions. Bilateral carotid ligation stimulated renal nerve release of both norepinephrine and dopamine in saline-expanded rats. The effects of carotid ligation and vagotomy were not additive with respect to norepinephrine release by renal nerves. However, the baroreflex-stimulated renal nerve release of dopamine was abolished by vagotomy. Electrical stimulation of the left cervical vagus with a square wave electrical pulse (0.5 ms duration, 10 V, 2 Hz) increased dopamine excretion exclusively from the innervated kidney of hydropenic rats. No significant change in norepinephrine excretion was observed during vagal stimulation. Increased dopamine excretion during vagal stimulation was associated with a larger natriuretic response from the innervated kidney than from its denervated mate (p less than 0.05). We conclude that under appropriate conditions vagal afferents stimulate renal release of dopamine and produce a neurogenically mediated natriuresis.     

Capsaicin and the stomach. A review of experimental and clinical data

Capsaicin, the pungent principle of hot pepper, because of its ability to excite and later defunctionalize a subset of primary afferent neurons, has been extensively used as a probe to elucidate the function of these sensory neurons in a number of physiological processes. In the rat stomach, experimental data provided clear evidence that capsaicin-sensitive (CS) sensory nerves are involved in a local defense mechanism against gastric ulcer. Stimulation of CS sensory nerves with low intragastric concentrations of capsaicin protected the rat gastric mucosa against injury produced by different ulcerogenic agents. High local desensitizing concentrations of capsaicin or systemic neurotoxic doses of the agent markedly enhanced the susceptibility of the rat gastric mucosa to later noxious challenge. Resiniferatoxin, a potent analogue of capsaicin possesses an acute gastroprotective effect similar to that of capsaicin in the stomach. The gastroprotective effect of capsaicin-type agents involves an enhancement of the microcirculation effected through the release of mediator peptides from the sensory nerve terminals with calcitonin gene-related peptide being the most likely candidate implicated. They do not depend on vagal efferent or sympathetic neurons or involve prostanoids. The gastric mucosal protective effect of prostacyclin is retained after systemic or topical capsaicin desensitization. Capsaicin-sensitive fibers are involved in the repair mechanisms of the gastric mucosa. A protective role for CS sensory nerves has also been demonstrated in the colon. In most studies, capsaicin given into the stomach of rats or cats inhibited gastric acid secretion. In humans, although recent studies provide evidence in favor of a beneficial effect of capsaicin on the gastric mucosa, an exact concentration-related assessment of the effect of the agent is still lacking.