Residual Gastric Dilatation Interferes with Metabolic Improvements Following Sleeve Gastrectomy by Upregulating the Expression of Sodium-Glucose Cotransporter-1.

OBJECTIVE: Sleeve gastrectomy (SG) is widely used in treating obesity because of significant weight loss and anti-diabetic effects, but there are still cases of long-term weight loss failure. Our aim was to explore the weight loss mechanism following SG in mice to learn how initial improvements in glucose metabolism are reversed in the long term. METHODS: C57/BL6 mice were divided into two groups, one undergoing SG and the other sham surgery. Body weight, gastric volume, blood glucose level, and the expression of sodium-glucose cotransporter 1 (SGLT1) were assessed at 2 weeks, 1 month, and 2 months after surgery. RESULTS: The SG mice had reduced food intake and lost weight during the 30 days after surgery. However, food intake and weight recovered gradually and even surpassed the sham group after 30 days. SGLT1 expression decreased within 1 month after SG and then increased at 2 months. Although initial SGLT1 expression levels in the stomach were much lower than at intestinal sites, levels increased following surgery and then decreased. The gastric volume decreased after SG, but was significantly increased at 2 months, exceeding the gastric volume in the sham mice. CONCLUSIONS: The metabolic benefits of SG are achieved through reduced gastrointestinal glucose absorption as evidenced by decreased expression of SGLT1 without bypassing the proximal intestine as in other forms of bariatric surgery. In addition, SGLT1 expression in the stomach may play a greater role in post-surgical metabolic effects, but further studies are needed.

Prognostic value of canine pancreatic lipase immunoreactivity and lipase activity in dogs with gastric dilatation-volvulus.

This study evaluated the association between a selection of candidate predictor variables, including the elevation of specific pancreatic enzymes, and outcome in dogs with gastric dilatation-volvulus (GDV). Twenty-two dogs with gastric dilatation-volvulus were included, being classified as survivors or non-survivors based on the final outcome. Dogs with intestinal obstruction (n = 16) were selected for comparison. Blood samples were collected upon admission (T0) and after 24 hours (T1). Serum lipase activity, canine pancreatic lipase immunoreactivity (cPLI) and other variables (plasma lactate concentration and C- reactive protein -CRP- in particular) were evaluated as predictive variables. T0 cPLI and serum lipase activity were not found to differ significantly between dogs with gastric dilatation-volvulus or intestinal obstruction. Canine pancreatic lipase immunoreactivity values above 400 µg/L were detected in 6/22 dogs with gastric dilatation-volvulus and 4/16 with intestinal obstruction. However, lactate concentration was significantly higher and CRP significantly lower in GDV as compared to IO dogs, and in the GDV group, lipase, cPLI and CRP measured upon admission were significantly associated with a negative outcome. No differences in lipase activity and canine pancreatic lipase immunoreactivity values were detected between T0 and T1. Presurgical cPLI and lipase activity were frequently increased during gastric dilatation-volvulus and were suggestive of the presence of pancreatic damage; while more extensive studies are required, based on this pilot analysis, cPLI has the potential to be a useful predictive variable for outcome in GDV. Further to this, serum CRP was able to predict outcome in this population of dogs with GDV, while blood lactate was not.

Nesfatin-1 regulates the lateral hypothalamic area melanin-concentrating hormone-responsive gastric distension-sensitive neurons and gastric function via arcuate nucleus innervation.

Nesfatin-1, a recently discovered neuropeptide involved in satiety. Recent studies have revealed that central nesfatin-1 inhibits gastric emptying and gastric acid secretion, though the mechanisms involved in these processes are not known. We aim to explore the effects of nesfatin-1 on a population of gastric distension (GD)-sensitive neurons in the lateral hypothalamus (LHA), gastric motility, and gastric secretion and the role for an arcuate nucleus (Arc)-LHA neural pathway in these processes. Single unit extracellular discharge recordings were made in of LHA. Further, gastric motility and gastric secretion in rats were monitored. Retrograde tracing and fluorescent immunohistochemical staining were used to explore nesfatin-1 neuron projection. The results revealed that administration of nesfatin-1 to the LHA or electric stimulation of the Arc could alter the neuronal activity of melanin-concentrating hormone (MCH)-responsive, GD-responsive neurons in LHA, which could be blocked by pretreatment with MCH receptor-1 antagonist PMC-3881-PI or weakened by pretreatment of a nesfatin-1 antibody in LHA. Administration of nesfatin-1 into LHA could inhibit gastric motility and gastric secretion, and these effects could be enhanced by administration of PMC-3881-PI. Electrical stimulation of Arc promoted the gastric motility and gastric secretion. Nesfatin-1 antibody or PMC-3881-PI pretreatment to LHA had no effect on Arc stimulation-induced gastric motility, but these pretreatments did alter Arc stimulation-induced effects on gastric secretion. Our findings suggest that nesfatin-1 signaling in LHA participates in the regulation of efferent information from the gastrointestinal tract and gastric secretion which also involve MCH signaling. Further, they show that a nesfatin-1-positive Arc to LHA pathway is critical for these effects.

The sum of its parts--effects of gastric distention, nutrient content and sensory stimulation on brain activation.

UNLABELLED: During food consumption the brain integrates multiple interrelated neural and hormonal signals involved in the regulation of food intake. Factors influencing the decision to stop eating include the foods' sensory properties, macronutrient content, and volume, which in turn affect gastric distention and appetite hormone responses. So far, the contributions of gastric distention and oral stimulation by food on brain activation have not been studied. The primary objective of this study was to assess the effect of gastric distention with an intra-gastric load and the additional effect of oral stimulation on brain activity after food administration. Our secondary objective was to study the correlations between hormone responses and appetite-related ratings and brain activation. Fourteen men completed three functional magnetic resonance imaging sessions during which they either received a naso-gastric infusion of water (stomach distention), naso-gastric infusion of chocolate milk (stomach distention + nutrients), or ingested chocolate-milk (stomach distention + nutrients + oral exposure). Appetite ratings and blood parameters were measured at several time points. During gastric infusion, brain activation was observed in the midbrain, amygdala, hypothalamus, and hippocampus for both chocolate milk and water, i.e., irrespective of nutrient content. The thalamus, amygdala, putamen and precuneus were activated more after ingestion than after gastric infusion of chocolate milk, whereas infusion evoked greater activation in the hippocampus and anterior cingulate. Moreover, areas involved in gustation and reward were activated more after oral stimulation. Only insulin responses following naso-gastric infusion of chocolate milk correlated with brain activation, namely in the putamen and insula. In conclusion, we show that normal (oral) food ingestion evokes greater activation than gastric infusion in stomach distention and food intake-related brain areas. This provides neural evidence for the importance of sensory stimulation in the process of satiation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01644539.

Role of transient receptor potential A1 in gastric nociception.

Afferent fibers innervating the gastrointestinal tract have major roles in consciously evoked sensations including pain. However, little is known about the molecules involved in mechanonociception from the upper gastrointestinal tract. We recently reported that activation of extracellular signal-regulated kinase 1/2 (ERK1/2), a member of the mitogen-activated protein kinase cascade in primary afferent neurons, was induced by noxious gastric distention in the rat, and that the activation of ERK1/2 in dorsal root ganglion (DRG) neurons can be implicated in acute visceral pain. Transient receptor potential (TRP) A1, a member of the TRP family of cation channels, was expressed in both DRG and nodose ganglion (NG) neurons innervating the stomach and in nerve fibers in the gastric wall. TRPA1 was coexpressed with ERK1/2 in gastric primary afferent neurons, and attenuation of TRPA1 activation using antisense peptides and a specific blocker led to suppression of both ERK1/2 activation and visceromotor responses. TRPA1 also significantly colocalized with substance P (SP) and calcitonin gene-related peptide (CGRP) in the thoracolumbar DRG, NG and stomach. These data indicate that SP and CGRP may also be released by TRPA1 activation in primary afferent neurons to elicit neurogenic inflammation and promote visceral hyperalgesia.

[Effects and mechanisms of Herba dendrobii on rats with stomach-heat syndrome].

OBJECTIVE: To observe the effects of Herba dendrobii on rats with stomach-heat syndrome and to explore the mechanisms. METHOD: Rats were fed with decoction of Rhizoma Zingiberis for 15 continuous days to induce the model of stomach-heat syndrome. After modeling, Herba Dendrobii (HD) decoction were given (in the doses of 1.5, 0.75 g x kg(-1) respectively) for 10 days. After treatment, amount of the daily diet, volume and absorbance of urine, pellet number and moistness of excrement, color and coating degree of tongue were recorded; the body thermal effects were detected with thermal texture maps (TTM) system; the biochemical indexes of blood reflecting the physiological function of stomach, including thromboxaneB2 (TXB2), 6-keto-prostaglandin F1alpha(6-keto-PGF1alpha), motilin (MTL), gastrin (Gas), somatostation (SS), interleukin-4 (IL-4) and interleukin-8 (IL-8) were measured by radio immunoassay; and the histological changes of gastric mucosa were observed by hematoxylin-eosin (HE) stain. RESULT: The model rat had yellow coating and red tongues (P < 0.05). The amount of daily diet were increased (over 10%), urine volume and excrement pellet number were decreased (over 10%). The their urine color became deep (P < 0.01) and their excrement became dry. The temperatures in head, neck, left fore-armpit, chest, up-abdomen, mid-abdomen of the model rats were raised up (difference > 0.5 degrees C or difference > 1.0 degree C ). The content of 6-keto-PGF1alpha in blood of model rats decreased evidently (P < 0.01), and the contents of MTL, Gas and IL-8 increased conspicuously (P < 0.01). The histological changes of gastric mucosa in the model rats were as follows: diffuse congestion, infiltration of neutrophil, less secretion, decrease of the number of chief and parietal cells, etc (P < 0. 05 or P < 0.01). After treatment with HD, except the daily food weight, the temperatures in head, neck and chest, the content of MTL and the number of chief cells, the other indexes observed above were improved noticeably (difference > 0.5 RC or difference > 1.0 degree C, P < 0.05 or P < 0.01). CONCLUSION: The reason why HD relieves the general symptom and sign the gastric mucosa of rats with stomach-heat syndrome is that HD can increase 6-keto-PGF1alpha and decrease IL-8, Gas, TXB2 in their blood.

Transient receptor potential A1 mediates gastric distention-induced visceral pain in rats.

BACKGROUND: Transient receptor potential (TRP)A1, a member of the TRP family of ion channels, has been proposed to function in diverse sensory processes, including thermosensation and pain. However, TRPA1 has not been directly implicated in stomach mechanosensation, and its contribution to acute visceral pain from this organ is unknown. Here, we investigated the expression of TRPA1 in primary sensory afferents and its involvement in visceral hypersensitivity in rats. METHODS: We examined TRPA1 expression in the dorsal root ganglion (DRG), nodose ganglion (NG), and stomach of rats by using immunohistochemistry. Electromyographic responses to gastric distention (GD) were recorded from the acromiotrapezius muscle in TRPA1 knockdown rats and in control rats. RESULTS: TRPA1 was predominantly expressed with sensory neuropeptides in DRG and NG neurons, and in nerve fibres in the rat stomach. Gastric distention induced the activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) in DRG and NG neurons 2 min after stimulation, and most of the phosphorylated-ERK1/2-labelled DRG neurons were TRPA1-positive neurons. Intrathecal injection of TRPA1 antisense attenuated the visceromotor response, and suppressed ERK1/2 activation in the DRG, but not NG, neurons produced by GD. Furthermore, intrathecal and intraperitoneal injections of the TRPA1 inhibitor HC-03003 suppressed the response to noxious GD. CONCLUSIONS: The activation of TRPA1 in DRG neurons by noxious GD may be involved in acute visceral pain. Our findings point to the potential blockade of TRPA1 in primary afferents as a new therapeutic target for the reduction of visceral hypersensitivity.

Dual role of nitric oxide in gastric hypersecretion in the distended stomach: inhibition of acid secretion and stimulation of pepsinongen secretion.

AIMS: We investigate the role of nitric oxide (NO) in the hypersecretion of acid and pepsinogen induced by stomach distension. MAIN METHOD: The rat stomach was distended by instillation of saline through an acute fistula under urethane anesthesia. KEY FINDINGS: Both secretions of acid and pepsinogen were increased by the distension depending on the volume of saline introduced, and responses were attenuated by bilateral cervical vagotomy or prior administration of atropine. N(G)-nitro-l-arginine methyl ester (L-NAME) had a dual effect on these responses, causing an increase in the acid response and a decrease in the pepsin response, both in an l-arginine-sensitive manner. Distension of the stomach increased the luminal NO release; this response was suppressed by vagotomy and L-NAME. Intragastric application of FK409, a NO donor, dose-dependently increased pepsinogen secretion while decreasing acid secretion in the stomach without distension. However, serosal application of both FK409 and 8-bromo-guanosine cyclic 3', 5'-monophosphate (8-Br-cGMP) stimulated the secretion of pepsinogen in isolated mouse stomachs in vitro. The stimulatory effect of FK409 on pepsinogen secretion was totally abolished by LY83583, a guanylate cyclase inhibitor. SIGNIFICANCE: Distension of the stomach increases both acid and pepsinogen secretion through a vagal-cholinergic pathway in addition to the luminal release of NO, and NO affects these responses in opposite ways, suppressing the acid response while enhancing the pepsin response, both mediated by a guanylate cyclase/cGMP pathway.

The effect of gastric dilatation in rats submitted to gasified water ingestion under the hepatic metabolic function / Efeito da dilatação gástrica em ratos submetidos à ingestão de água gaseificada sobre a função metabólica hepática

INTRODUCTION: The amounts of people that are overweight have been increasing within the population in significant ways during the last decades. In this view, gasified beverages have become an important environmental concern in relation to the eating habits of people, especially who lives in the USA, Mexico, and Brazil. In this order, these three countries constitute the major beverages producers and consumers of the whole world. PURPOSE: To investigate the effects of gastric dilatation in rats submitted to gasified water ingestion, uniform vehicle for all soft drinks, under metabolic patterns of the hepatic function. METHODS: Two groups of 15 rats were formed and observed during two weeks. The rats of the group I, were fed with 200g/day of rat food ad libitum and 100ml of non-gasified water during three daily periods. The rats composing the group II, were fed with 200g/day of rat food ad libitum and 100ml of gasified water within 3 daily periods. The media (x) and standard deviation (s) were calculated through the paired t-test for each group in order to compare the effects of the different types of water and its effect in each one of them. RESULTS: The results indicated that the animals which were submitted to the treatment with gasified water (G-II), presented an increase of glutamic-pyruvic transaminase (GPT) and alkaline phosphatase (ALP) (p<0,01), tendency to increase the glutamic-oxaloacetic transaminase (GOT) (0,10>p>0,05) and increase of the gastric area with macroscopic morphologic alterations, such as the loss of the characteristic linear depressions on the surface of the mucous membrane. CONCLUSION: The gasified water favored the expansion of the gastric area and contributed to the extinction of the linear depressions of the mucous organ, which caused metabolic alterations of the hepatic function.

INTRODUÇÃO: O excesso de peso na população aumentou de forma significante nas últimas décadas e as bebidas gasosas tornaram-se um fator ambiental importante no comportamento alimentar das pessoas, sendo os EUA, México e Brasil, nesta ordem, os três maiores paises produtores e consumidores de refrigerantes. OBJETIVO: Investigar os efeitos da dilatação gástrica em ratos submetidos a ingestão de água gaseificada, veículo uniforme para todos os refrigerantes, sobre parâmetros metabólicos da função hepática. MÉTODOS: Foram constituídos dois grupos de 15 ratos acompanhados por 15 semanas. Ao Grupo-I, foram oferecidos 200 g/dia de ração ad libitum e 100 ml de água não gaseificada em 3 períodos diários, ao Grupo-II, foram oferecidos 200 g/dia de ração ad libitum e 100 ml de água gaseificada em 3 períodos diários; em cada grupo,foram calculados a média (x) e o desvio padrão (s); para todos os atributos estudados foi utilizado o método estatístico de teste t pareado, comparando-se GI com GII, testando-se o efeito dos tipos de água. RESULTADOS: Os resultados identificaram que os animais que foram submetidos ao tratamento com água gaseificada (Grupo-II), apresentaram um aumento de transaminase glutâmica pirúvica (TGP) e fosfatase alcalina p<0,01), tendência de aumento da transaminase glutâmica oxalacética (TGO) (0,10>p>0,05) e aumento da área gástrica com alterações morfológicas macroscópicas como o desaparecimento do pregueamento mucoso característico. CONCLUSÃO: A água gaseificada favoreceu o aumento da área gástrica com conseqüente desaparecimento macroscópico do pregueamento mucoso do órgão, que ocasionou alterações metabólicas da função hepática.

The effect of gastric dilatation in rats submitted to gasified water ingestion under the hepatic metabolic function.

INTRODUCTION: The amounts of people that are overweight have been increasing within the population in significant ways during the last decades. In this view, gasified beverages have become an important environmental concern in relation to the eating habits of people, especially who lives in the USA, Mexico, and Brazil. In this order, these three countries constitute the major beverages producers and consumers of the whole world. PURPOSE: To investigate the effects of gastric dilatation in rats submitted to gasified water ingestion, uniform vehicle for all soft drinks, under metabolic patterns of the hepatic function. METHODS: Two groups of 15 rats were formed and observed during two weeks. The rats of the group I, were fed with 200g/day of rat food ad libitum and 100ml of non-gasified water during three daily periods. The rats composing the group II, were fed with 200g/day of rat food ad libitum and 100ml of gasified water within 3 daily periods. The media (x) and standard deviation (s) were calculated through the paired t-test for each group in order to compare the effects of the different types of water and its effect in each one of them. RESULTS: The results indicated that the animals which were submitted to the treatment with gasified water (G-II), presented an increase of glutamic-pyruvic transaminase (GPT) and alkaline phosphatase (ALP) (p<0,01), tendency to increase the glutamic-oxaloacetic transaminase (GOT) (0,10>p>0,05) and increase of the gastric area with macroscopic morphologic alterations, such as the loss of the characteristic linear depressions on the surface of the mucous membrane. CONCLUSION: The gasified water favored the expansion of the gastric area and contributed to the extinction of the linear depressions of the mucous organ, which caused metabolic alterations of the hepatic function.

Gastric distention enhances FOS and calcitonin gene-related peptide expression in the spinal cord and brain of rats.

OBJECTIVE: The purpose of this study was to determine the pathway and mode of transmission of visceral stimuli by investigating the distribution of the FOS and calcitonin gene-related peptide (CGRP) proteins in the central nervous system. METHODS: Twenty-four Sprague-Dawley rats were divided into three groups: study group (n = 12), sham control group (n = 6), and normal control group (n = 6). A balloon was implanted into the stomach of the rats in the study and sham control groups. After 48 h, the rats in the study group had the stomach distended (80 mmHg) for 2 h, after which they were killed and the antrum, thoracic spinal cord and brain were isolated or dissected. The expression of Fos and CGRP in these tissues was detected immunohistochemically. RESULTS: FOS expression in the dorsal horn of the spinal cord, dorsal nucleus of the vagal nerve, nucleus of the solitary tract in the study rats was significantly higher than in the sham and normal controls. However, no difference was found between the three groups in FOS expression in the myenteric plexus. Similarly, gastric distention enhanced CGRP expression significantly in the spinal cord and medulla oblongata and correlated closely with FOS expression in these two areas. CONCLUSIONS: Gastric distention can activate the limbic system, and CGRP plays an important role in the input of visceral stimuli.

The effect of experimental gastric dilatation-volvulus on adenosine triphosphate content and conductance of the canine gastric and jejunal mucosa.

The objective of this study was to determine if experimental gastric dilatation volvulus (GDV) would decrease adenosine triphosphate (ATP) concentration and increase membrane conductance of the canine gastric and jejunal mucosa. Male dogs (n = 15) weighing between 20 and 30 kg were used. Dogs were randomly assigned to 1 of 3 equal groups: Group 1 was control, group 2 was GDV, and group 3 was ischemia. All dogs were anesthetized for 210 min. Group 1 had no manipulation. Group 2 had GDV experimentally induced for 120 min followed by decompression, derotation, and reperfusion for 90 min. Group 3 had GDV experimentally induced for 210 min. Gastric (fundus and pylorus) and jejunal tissue was taken at 0, 120, and 210 min from all of the dogs. Tissue was analyzed for ATP concentration, mucosal conductance, and microscopic changes. The ATP concentration in the fundus did not change significantly from baseline in group 2, but decreased significantly below baseline at 210 min in group 3. The ATP concentration in the jejunum decreased significantly below baseline in groups 2 and 3 at 120 min, remaining significantly decreased in group 3 but returning to baseline at 210 min in group 2. Mucosal conductance of the fundus did not change significantly in any dog. Mucosal conductance of the jejunum increased at 120 min in groups 2 and 3, and became significantly increased above baseline at 210 min. The jejunal mucosa showed more profound cellular changes than the gastric mucosa. The jejunum showed substantial decreases in ATP concentration with an increase in mucosal conductance, suggesting cell membrane dysfunction. Dogs sustaining a GDV are likely to have a change in the activity of mucosal cells in the jejunum, which may be important in the pathophysiology of GDV.

Gastric distension induces c-Fos in medullary GLP-1/2-containing neurons.

A group of neurons in the caudal nucleus of the solitary tract (NTS) processes preproglucagon to glucagon-like peptides (GLP)-1 and -2, peptides that inhibit food intake when administered intracerebroventricularly. The GLP-1/2-containing neural pathways have been suggested to play a role in taste aversion and nausea because LiCl activates these neurons, and LiCl-induced suppression of food intake can be blocked by the GLP-1 receptor antagonist exendin-9. As many gastrointestinal signals related to both satiety and nausea/illness travel via the vagus nerve to the caudal medulla, the present study assessed the capacity of different types of gastric distension (a purely mechanical stimulus) to activate GLP-1 neurons in the caudal NTS. Gastric balloon distension (1.4 ml/min first 5 min, 0.4 ml/min next 5 min, 9 ml total, held for 60 min) in nonanesthetized, freely moving rats produced 12- and 17-fold increases in c-Fos-expressing NTS neurons when distension was mainly in the fundus or corpus, respectively. Fundus and corpus distension increased the percentage of c-Fos-activated GLP-1 neurons to 21 +/- 9% and 32 +/- 5% compared with 1 +/- 1% with sham distension (P < 0.01). Thus gastric distension that may be considered within the physiological range activates GLP-1/2-containing neurons, suggesting some role in normal satiety. The results support the view that the medullary GLP system is involved in appetite control and is activated by stimuli within the behavioral continuum, ranging from satiety to nausea.

Mechanisms for regulation of gastrin and somatostatin release from isolated rat stomach during gastric distention.

AIM: To investigate the intragastric mechanisms for regulation of gastric neuroendocrine functions during gastric distention in isolated vascularly perfused rat stomach. METHODS: Isolated vascularly perfused rat stomach was prepared, then the gastric lumen was distended with either 5,10 or 15 ml pH7 isotonic saline during a period of 20 min. During the distention, the axonal blocker tetrodotoxin (TTX), the cholinergic antagonist atropine, or the putative somatostatin-antagonist cyclo (7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl)) were applied by vascular perfusion. The releases of gastrin and somatostatin were then examined by radioimmunoassay. RESULTS: The graded gastric distention caused a significant volume-dependent decrease in gastrin secretion (-183+/-75 (5 ml), -385+/-86 (10 ml) and -440+/-85 (15 ml) pg/20 min) and a significant increase of somatostatin secretion (260+/-102 (5 ml), 608+/-148 (10 ml) and 943+/-316 (15 ml) pg/20 min). In response to 10 ml distention, the infusion of either axonal blocker TTX (10(-6) M) or cholinergic blocker atropine (10(-7) M) had a similar affect. They both attenuated the decrease of gastrin release by approximately 50 %, and attenuated the increase of somatostatin release by approximately 40 %. The infusion of somatostatin-antagonist cyclo (7-aminoheptanoyl-Phe-D-Trp-Lys-Thr (Bzl)) (10(-6)M) attenuated the decrease of gastrin release by about 60 %. Furthermore, combined infusion of the somatostatin-antagonist and atropine completely abolished distention-induced inhibition of gastrin release. CONCLUSION: The present data suggest that distention of isolated rat stomach stimulates somatostatin release via cholinergic and non-cholinergic TTX-insensitive pathways. Both somatostatin and intrinsic cholinergic pathways are responsible for distention-induced inhibition of gastrin release.

[Capsaicin-sensitive afferent fibers and endogenous NO mediate the gastric acid secretion and gastric mucosal blood flow in intragastric distention in rats].

AIM AND METHODS: By hydrogen gas clearance technique to measure gastric mucosal blood flow (GMBF) and a high dose of capsaicin to ablate the capsaicin-sensitive afferent fibers, the roles of capsaicin-sensitive afferent fibers and endogenous NO in the gastric acid secretion and hyperemic response to intragastric distention were studied in rats. RESULTS: (1) There was an increase in acid secretion associated with the increase in GMBF to intragastric distention. (2) Pretreatment with a high dose of capsaicin to ablate afferent fibers completely abolished the GMBF and partially inhibited the acid secretion during the intragastric distention. (3) The increase in GMBF to intragastric distention was completely blocked by pretreatment with L-NAME, whereas the acid secretion was significantly attenuated. CONCLUSION: Capsaicin-sensitive afferent fibers and endogenous NO are involved in the increases of gastric acid secretion and GMBF.

Intracellular magnesium concentrations in dogs with gastric dilatation-volvulus.

OBJECTIVE: To quantify and compare intracellular magnesium concentrations (Mgi) in clinically normal dogs (control dogs) and dogs that have gastric dilatation-volvulus (GDV dogs) and to determine whether there is a difference in Mgi and serum magnesium concentrations (Mgs) between GDV dogs with and without cardiac arrhythmias. ANIMALS: 41 control dogs and 21 GDV dogs. PROCEDURE: Rectus abdominis muscle specimens were obtained from control and GDV dogs for determination of Mgi. Blood samples were obtained from GDV dogs for determination of Mgs, and dogs were monitored for 48 hours for cardiac arrhythmias. Muscle specimens were frozen at -40 C, oven dried at 95 C, and digested with concentrated nitric acid. Multielemental analyses were performed by simultaneous/sequential inductively coupled plasma-atomic emission spectroscopy with fixed-cross flow nebulization. The Mg, was standardized to sulfur content to correct for the amount of fat and fascia in the muscle specimen. Mean (+/- SEM) values were recorded in parts per million (ppm). Results-There were no significant differences in Mgi between control (627 +/- 11.1 ppm) and GDV (597 +/- 20.5 ppm) dogs, in Mgi between GDV dogs with (590 +/- 34 ppm) and without (584 +/- 29 ppm) cardiac arrhythmias, and in Mgs between GDV dogs with (1.77 +/- 0.26 ppm) and without (1.51 +/- 0.09 ppm) cardiac arrhythmias. There was no correlation between Mgs and Mgi (R2 = 0.0001). CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that Mg depletion is not pathophysiologically important in dogs with GDV and does not play a role in the cardiac arrhythmias detected in these patients.

Modulation by endogenous nitric oxide of acid secretion induced by gastric distention in rats: enhancement by nitric oxide synthase inhibitor.

The mechanism underlying acid hypersecretion induced by gastric distention was investigated in rats, especially in relation to endogenous nitric oxide (NO). Under urethane anesthesia, rat stomach was distended by instillation of saline (1-10 ml) through the acute fistula that was provided through a pylorus. Gastric samples were collected every 1 h, and the acid secretion was measured by titration with 100 mM NaOH. Gastric acid secretion was increased by distention, and the degree of stimulation was dependent on the volume of saline instillation; a maximal response occurred with 6-ml instillation, which maintained the intraluminal pressure of about 20 cm H(2)O. The increased acid secretory response induced by distention was completely blocked by omeprazole and significantly mitigated by vagotomy, sensory deafferentation, atropine, or famotidine but markedly enhanced by the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). On the other hand, the enhanced acid response in the presence of L-NAME occurred in an L-arginine-sensitive manner and was almost totally abolished by vagotomy and sensory deafferentation as well as by atropine. Gastric distention increased the release of NO metabolites and histamine into the gastric lumen. The NO metabolite release in the distended stomach was significantly decreased by vagotomy or L-NAME, whereas the histamine output was decreased by vagotomy but increased by L-NAME in an L-arginine-sensitive manner, respectively. These results suggest that 1) gastric distention increases acid secretion, initially through the perception by sensory neurons of the mechanical stimulation and mainly through the efferent vagocholinergic pathway, with the process being modified by endogenous NO, and 2) this molecule, released in a vagal-dependent manner, exerts a negative influence on acid secretion, at least in part by suppressing histamine release from the histamine-containing cells.

Role of central oxytocin in the inhibition by endotoxin of distension-stimulated gastric acid secretion.

The gastric acid hyposecretory state associated with endotoxemia is mediated by a nervous reflex involving the central nervous system. The aim of the present study was to analyse the central effects of different peptides on distension-stimulated gastric acid secretion and the endogenous role of such peptides on the hyposecretory effects of endotoxin. The effect of an intracisternal (i.c.) administration of oxytocin, vasopressin, corticotropin releasing factor (CRF), bombesin, somatostatin and the opioid receptor agonist BW443C or an intravenous (i.v.) injection of a small dose of endotoxin on distension-stimulated gastric acid secretion was studied in the continuously perfused stomach of anaesthetised rats. In some animals, specific receptor antagonists for oxytocin (Compound VI [d(CH2)5, Tyr(Me)2, Thr4, Tyr-NH2(9)]-OVT, 0.01-1 microg/rat), vasopressin (des-Gly9-[beta-Mercapto-beta,beta-cyclopentamethylene-propiony l1, O-Et-Tyr2, Val4, Arg8]-VP, 20 microg/rat), CRF (alpha-helical CRF [9-41], 50 microg/rat) or bombesin (D-Phe12-Bombesin, 20 microg/rat) were administered i.c. before endotoxin. Distension-stimulated acid secretion was significantly inhibited by central oxytocin (0.2, 2 or 4 nmol/rat, 45+/-16%, 69+/-10% and 79+/-5% reduction, respectively), CRF (0.5, 1 or 2 nmol/rat, 52.2+/-15.6%, 74.3+/-9.1% and 93.2+/-1.6% reduction, respectively) and bombesin (2 nmol/rat, 79.1+/-5.8% reduction). The hyposecretory effect induced by endotoxin (5 microg/kg, 60.2+/-2.3% reduction) was reversed in a dose-dependent manner by pretreatment with the oxytocin receptor antagonist (0.01, 0.1 and 1 microg/rat, 65.2+/-14.4%, 88.0+/-22.5% and 112.4+/-25.2% of control response, respectively) while the vasopressin (20 microg/rat), CRF (50 microg/rat) or bombesin (20 microg/rat) receptor antagonists had no effect. The present results support a role for the endogenous release and action in the central nervous system of oxytocin in the inhibitory effect of endotoxin on gastric acid secretion.

Cholecystokinin-A receptors modulate gastric sensory and motor responses to gastric distension and duodenal lipid.

BACKGROUND & AIMS: The combination of duodenal lipid and gastric distention induces meal-like fullness followed by nausea in healthy subjects. The aim of this study was to assess the role of cholecystokinin (CCK) A receptors in these changes using a CCK-A antagonist loxiglumide. METHODS: Twelve healthy subjects were studied on four occasions, during which either 0.9% saline or 20% Intralipid was infused intraduodenally on two occasions each (1 mL/min) while the proximal stomach was distended with air (100 mL/min). During each duodenal infusion, subjects received intravenous loxiglumide (10 mg.kg-1.h-1) on 1 day and placebo on the other. Intragastric pressure changes were recorded, and the subjects reported gastric sensations (fullness, nausea). RESULTS: Loxiglumide did not influence gastric motility or sensitivity during duodenal saline infusion. Duodenal lipid reduced gastric tonic and phasic pressure activity during distensions and induced meal-like fullness and nausea; sensations were reported at similar volumes but lower intragastric pressures (P < 0.001 vs. saline). Loxiglumide partially restored gastric tonic and phasic activity during lipid infusion, reduced the occurrence of meal-like fullness and nausea, and increased the pressures at which sensations were reported (P < 0.001 vs. placebo). CONCLUSIONS: CCK-A receptors are involved in the induction of meal-like fullness and nausea associated with intraduodenal lipid and gastric distention.

Gross and histologic evaluation of hepatogastric ligaments in clinically normal dogs and dogs with gastric dilatation-volvulus.

OBJECTIVE--To investigate any potential structural differences in hepatogastric ligaments between clinically normal dogs and dogs with gastric dilatation-volvulus (GDV). DESIGN--Case-control study. ANIMALS--Hepatogastric ligaments were examined in 13 large-breed control dogs and in 13 large-breed dogs referred for surgical treatment of GDV. PROCEDURE--Measurements and biopsies of hepatogastric ligaments were performed at the time of surgery, circumcostal gastropexy, for correction of GDV. Serial sections from each ligament were stained with H&E, Masson's trichrome, and elastin stains to assess morphology, including smooth muscle, collagen, and elastic fiber contents. RESULTS--There were no differences observed by light microscopy in incidence or degree of histopathologic alterations between the 2 groups of dogs. The lengths of hepatogastric ligaments in GDV-affected dogs, however, were significantly longer than those of control dogs (GDV-affected dogs, 7.0 [5.0 to 9.5] cm median [range]; control dogs, 5.0 [3.0 to 7.5] cm median [range]; P = 0.01). CONCLUSIONS--Causality can not be inferred from this study. It is not known whether the ligaments were lengthened as a result of GDV or whether the lengthened ligaments predisposed dogs to GDV. CLINICAL RELEVANCE--This finding may reflect increased laxity of the supporting hepatogastric ligament in the right quadrant of the abdomen. An elongated ligament may permit increased stomach mobility and predispose dogs to partial or complete gastric volvulus.