Increase In Gastric Acid Secretion Research Articles

A Reappraisal of the Pathophysiology of Cushing Ulcer: A Narrative Review.

In 1932, Harvey Cushing described peptic ulceration secondary to raised intracranial pressure and attributed this to vagal overactivity, causing excess gastric acid secretion. Cushing ulcer remains a cause of morbidity in patients, albeit one that is preventable. This narrative review evaluates the evidence pertaining to the pathophysiology of neurogenic peptic ulceration. Review of the literature suggests that the pathophysiology of Cushing ulcer may extend beyond vagal mechanisms for several reasons: (1) clinical and experimental studies have shown only a modest increase in gastric acid secretion in head-injured patients; (2) increased vagal tone is found in only a minority of cases of intracranial hypertension, most of which are related to catastrophic, nonsurvivable brain injury; (3) direct stimulation of the vagus nerve does not cause peptic ulceration, and; (4) Cushing ulcer can occur after acute ischemic stroke, but only a minority of strokes are associated with raised intracranial pressure and/or increased vagal tone. The 2005 Nobel Prize in Medicine honored the discovery that bacteria play key roles in the pathogenesis of peptic ulcer disease. Brain injury results in widespread changes in the gut microbiome in addition to gastrointestinal inflammation, including systemic upregulation of proinflammatory cytokines. Alternations in the gut microbiome in patients with severe traumatic brain injury include colonization with commensal flora associated with peptic ulceration. The brain-gut-microbiome axis integrates the central nervous system, the enteric nervous system, and the immune system. Following the review of the literature, we propose a novel hypothesis that neurogenic peptic ulcer may be associated with alterations in the gut microbiome, resulting in gastrointestinal inflammation leading to ulceration.

The role of Cola nitida on gastric acid secretion and its mechanism of action in male Wistar rats

This study investigated the effect of an aqueous extract of Cola nitida (AECN) and decaffeinated (DECAF) extract of kolanut on gastric acid secretion and its mechanism of action in rats. Previous reporters only speculated that the biological effect of kolanut in causing gastric acid secretion could be ascribed to its caffeine content, also the mechanism is not fully elucidated. In addition, none of the previous reporters has investigated the effect of decaffeinated kolanut extract on gastric acid secretion. Sixty (60) male adult Wistar rats divided into twelve groups of five rats each were used for this study. Groups 1 and 2 received normal saline orally and intravenously respectively at a dose of (1 ml/kg), 3 and 4 received 25 mg/kg of (AECN) orally and intravenously respectively, group 5 received (100mg/kg) AECN orally, groups 6 and 7 received 25mg/kg of (DECAF) both orally and intravenously respectively, group 8 received 100mg/kg of DECAF orally, groups 9 and 10 were pre-treated with cimetidine 12 μmoles/kg intravenously followed by 25 mg/kg AECN and DECAF respectively, groups 11 and 12 were pre-treated with i.v atropine (0.2 mg/kg) followed by 25 mg/kg of AECN and DECAF respectively. Gastric acid secretion was determined by continuous perfusion of rats' stomachs under urethane anesthesia. Data collected were expressed as mean ± SEM. Statistical significance at P≤0.05 was determined using Student’s t-test analysis. The oral administration of AECN (25mg/kg and 100mg/kg) and i.v AECN (25mg/kg) caused a significant increase (P≤0.05) in gastric acid secretion (GAS) with pronounced effect than DECAF group. The oral administration of 25mg/kg and 100mg/kg of DECAF and intravenous administration of (25mg/kg) DECAF caused a significant increase in gastric acid secretion. The administration of cimetidine and atropine significantly reduced gastric acid secretion. In conclusion, aqueous extract of Cola nitida and decaffeinated kolanut extract exert significant gastric acid secretion in this study. Also, the mechanisms exhibited by kolanut in stimulating gastric acid secretion in this study could be attributed to stimulating both the histaminergic H2 and cholinergic (Muscarinic M3) receptors since cimetidine and atropine blocked/reduced its effect. This research work was self-funded. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

De Novo Gastric Acid Secretion Mediated by Dietary Acrylamide Induced Oxidative Stress in Stomach Tissue of Experimental Rats

Background: Acrylamide input on gastric mucosa lesion is known but not fully elucidated. In this study the impact of dietary acrylamide on gastric acid secretion; an aggressive factor capable of causing erosion of the stomach tissue was evaluated to explain possible reason why acrylamide could induce gastric mucosa lesion. Thus, the study focuses on the impact of dietary acrylamide on gastric acid secretion and its association with mucosa lesion.
 Materials and Methods: Fifteen (15) male Sprague-Dawley rats were grouped into three groups (n = 5). Group 1 (control) was fed with standard rat diet, Group 2 and 3 were fed with standard rat diet contaminated with acrylamide doses (7.5mg/kg and 15mg/kg respectively) reported to compromise gastric mucosa integrity. The experimental animals were allowed free access to their various feed and drinking water ad libitum for 4 weeks. Impact of the dietary acrylamide on gastric acid secretion, gastric acidity and stomach tissue oxidative stress biomarkers (lipid peroxidation (MDA), superoxide dismutase (SOD), Glutathione peroxidase (GPx), and Catalase, CAT) were determined.
 Results: Average dietary consumption across the groups was 90.88% per week. Acrylamide contaminated diet significantly increased gastric acid secretion and gastric acidity in a dose dependent manner when compared to control, P<0.01. Dietary acrylamide also induced oxidative stress on stomach tissues by significantly increasing MDA as well as decreasing SOD, GPx, and CAT of the stomach in a dose dependent manner when compared to control, P<0.01.
 Conclusion: Findings from the study suggests that oxidative stress induced on stomach tissue by dietary acrylamide could be as a result of the increase in gastric acid secretion and gastric acidity observed.

Recent Advances in the Gastric Mucosal Protection Against Stress-induced Gastric Lesions. Importance of Renin-angiotensin Vasoactive Metabolites, Gaseous Mediators and Appetite Peptides.

Stress is known to cause severe adverse effects in the human gastrointestinal tract including mucosal microbleedings and erosions or even gastric ulceration but the mechanism of these complications has not been fully elucidated. The pathogenesis of stress-induced gastric damage involves the fall in Gastric Blood Flow (GBF), an increase in gastric acid secretion and gastric motility, enhanced adrenergic and cholinergic nerve activity and the rise in gastric mucosal generation of reactive oxygen species. The gastric mucosal defense mechanisms against the deleterious effect of stress include the activation of the hypothalamic-pituitary-adrenal axis which has been linked with glucocorticoids release capable of counteracting of stress-induced gastric lesions. Here we summarize the novel gastroprotective mechanisms against stress damage exhibited by angiotensin-(1-7), the newly discovered metabolite of Renin-Angiotensin System (RAS), the gaseous mediators such as nitric oxide (NO), hydrogen sulfide (H2S) or Carbon Monoxide (CO), and the food intake controlling peptides ghrelin, nesfatin- 1 and apelin possibly acting via brain-gut axis. These bioactive molecules such as RAS vasoactive metabolite angiotensin-(1-7) and appetite peptides have been shown to afford gastroprotective effect against stressinduced gastric lesions mainly mediated by an increase in gastric microcirculation. Gaseous mediators protect the gastric mucosa against stress lesions by mechanism involving the activation of PG/COX and CO/HO-1 biosynthetic pathways, and their anti-inflammatory and anti-oxidizing properties. Thus, these new components add new mechanistic aspects to the common cooperation of NO/NO-synthase, PG/COX systems and vasoactive sensory neuropeptides including CGRP but their gastroprotective efficacy against experimental stress ulcerogenesis requires the confirmation in human clinical trials.

Evaluation of Long Term Alcohol Consumption on Gastric Acid Secretion and the Histomorphometry of the Stomach in Adult Male Wistar Rats

This study was aimed at investigating to check the effects of long term consumption of varying concentrations of alcohol on gastric acid secretions and the histomorphometry of the stomach of adult male Wistar rats, and the possible ameliorative effect of omega-3 fish oil. Eighty (80) adult male Wistar rats weighing 180-230 gm were used. The rats were divided into eight groups containing ten (10) rats each group. Group I served as the control; Groups II, III and IV were given 5%, 20% and 40% alcohol respectively; Groups V, VI and VII were given 5% alcohol+Omega-3 fish oil; 20% alcohol+Omega-3 fish oil and 40% alcohol+Omega-3 fish oil, respectively. The Group VIII was administered Omega-3 fish oil alone. The alcohol was given at a dose of 0.005 ml/g body weight once daily using an orogastric canular. The Omega-3 fish oil was given at a dose of 0.2 ml/g body weight. Alcohol administration lasted for twelve weeks, at the end of which the rats were sacrificed by cervical dislocation. Gastric secretions were estimated, and tissues samples from the stomach collected for histomorphometric studies. The results showed that 20% alcohol caused a significant increase in gastric acid secretion when compared with the control and omega-3 only group. 40% and omega-3 group caused a decrease in gastric acid secretion when compared with the control. The histomorphometry of the stomach revealed a decrease in parietal cell and mucous cell count with increasing alcohol concentrations. Omega-3 administration showed only mild amelioration to these digestive alterations.

A Chronological Increase in Gastric Acid Secretion from 1995 to 2014 in Young Japanese Healthy Volunteers under the Age of 40 Years Old.

Gastric acid secretion levels are an important determinant of the manifestation of acid-related upper GI diseases such as gastroesophageal reflux disease. We recently reported that gastric acid secretion levels did not change from the 1990s to 2010s in H. pylori-negative asymptomatic Japanese outpatients with a mean age of 63 years old. However, because young people have a quite different lifestyle, including dietary pattern, from elderly people in Japan, it is worth investigating any chronologic changes in gastric acid secretion in younger generations. The aim of this analysis is to investigate the potential changes in gastric acid secretion from 1995 to 2014 in young Japanese healthy volunteers. Eighty-eight young Japanese healthy volunteers under the age of 40 with a mean age of 26 were extracted from a database accumulated from 1995 to 2014 for the present analysis. Their gastrin-stimulated gastric acid level was determined with the endoscopic gastrin test. In 76 H. pylori-negative subjects, gastric acid secretion levels showed a significant positive correlation with the calendar year when the test was performed (r = 0.27, p < 0.01). A similar trend was observed in 12 H. pylori-positive subjects. A chronological 5-year time period showed a significant positive association with gastric acid secretion in univariate and multivariate analyses (p < 0.01 and p = 0.01, respectively). Gastric acid secretion levels have been increasing in young Japanese healthy volunteers during the last 20 years. We need to monitor future trends in the prevalence of acid-related diseases such as gastro-esophageal reflux disease in Japan.

No increase in gastric acid secretion in healthy Japanese over the past two decades.

The prevalence of gastroesophageal reflux disease (GERD) has been increasing worldwide over recent decades. A previous study demonstrated that gastric acid secretion, thought to be an important factor in the increase in the rate of GERD, in Japanese individuals increased in the era from the 1970s to the 1990s. The aim of this study was to evaluate whether gastric acid secretion has altered over the past two decades with and without the influence of Helicobacter pylori infection in nonelderly and elderly Japanese. Gastric acid secretion, the concentrations of serum gastrin, pepsinogen I, and pepsinogen II, and H. pylori infection were determined in 78 healthy Japanese subjects. The findings were compared with data obtained in the 1990s. Basal acid output (BAO) and maximal acid output (MAO) gradually decreased with age in H. pylori-negative subjects. In addition, those with H. pylori infection tended to show decreased gastric acid secretion as compared with those without infection, particularly in the elderly group. MAO decreased gradually with age in males, whereas it remained unchanged with age in females. MAO in H. pylori-negative subjects has not changed over the past two decades (17.7 mEq/h vs 17.6 mEq/h in nonelderly subjects, and 15.2 mEq/h vs 12.7 mEq/h in elderly subjects). In contrast to the increased prevalence of GERD, gastric acid secretion has not increased over the past two decades in Japanese. However, secretion has decreased with age in males but not in females, which may partly explain the sex difference in the age-related GERD prevalence.

EFFECT OF APELIN-13 ADMINISTRATION ON GASTRIC SECRETION IN NORMAL AND DIABETIC RATS

Background: Apelin is a recently discovered peptide, identified as an endogenous ligand of receptor APJ, apelin has beneficial effect in diabetic conditions as it increase glucose uptake and improve insulin sensitivity, diabetic patients have impaired gastric secretion and apelin is expressed in parietal, chief and mucous cells and this raise the possibility of involvement of apelin in gastric physiology. Objective: The present study was carried out to demonstrate the effect of acute and chronic administration of apelin 13 on gastric secretion in normal and diabetic rats. Design: 98 adult wistar male albino rats were used, animals were divided into three main groups group A (normal rats), group B (high fat diet induced diabetic rats) and group C (streptozotocin induced diabetic rats), each group is subdivided into control subgroup (1), acute apelin-13 injected subgroup (2), chronic apelin-13 injected subgroup for 21 days (3): In all studied groups, different parameters of gastric secretion, gastric mucosal pH and mucin content were measured. Results: acute administration of apelin-13 decreased gastric acid secretion in all groups proved by significant increase in pH accompanied by significant decrease in total and free acidity, the percentage in decrease of gastric acid secretion in normal rats is more than that of high fat diet induced diabetic rats and streptozotocin induced diabetic rats. Ghrelin level, volume of gastric secretion, blood glucose and HOMA- IR significantly decreased in all groups. pepsin, mucin content of gastric mucosa and insulin level had no significant change in all groups, while, pH of gastric mucosal surface significantly increased .In addition, there was negative correlation between ghrelin level and pH, positive correlation between ghrelin and both total and free acidity in normal rats, positive correlation between ghrelin and volume of gastric secretion in all studied groups. Chronic administration of apelin-13 caused no change in gastric acidity in normal rats. and increase gastric acidity in high fat diet induced diabetic rats and streptozotocin induced diabetic rats, proved by significant decrease in pH accompanied by significant increase in total and free acidity, the percentage of increase in gastric acid secretion in high fat diet induced diabetic rats is more than that of streptozotocin induced diabetic rats, moreover, chronic administration of apelin-13decreased ghrelin level, pepsin level, volume of gastric secretion, blood glucose, insulin level and HOMA- IR and increase pH of gastric mucosal surface and mucin level in all studied groups. In addition, there is positive correlation between ghrelin and volume of gastric secretion in all studied groups. Conclusion: While apelin-13 injection on chronic run caused no change in gastric acidity in normal rats, it improved gastric acidity in diabetic rats and can act as a promising target for type 2 diabetes treatment. In addition apelin-13 can be considered as gastro protective agent as it increased pH of gastric mucosal surface and mucin level in normal and diabetic rats. Key words: Apelin, gastric secretion, diabetes.

Gastric secretagogue action of Cryptolepis sanguinolenta in the perfused stomach of anesthetized rats

Background : Cryptolepis sanguinolenta has been reported to have antimalarial and antidiabetic effects. Aim : The gastric secretagogue action of ethanolic extract of Cryptolepis sanguinolenta stem was studied in rat model to evaluate its possible role in gastric acid secretion. Food intake and weight gain were also observed. Materials and Methods : The animals used were divided into four groups. The control received 2 ml of distilled water, while treated groups received 50, 150, and 250 mg/kgbw of Cryptolepis sanguinolenta extract per oral respectively daily for 21 days. Results : Cryptolepis sanguinolenta caused dose-dependent increase in gastric acid secretion. This secretagogue effect was augmented by histamine. Cryptolepis sanguinolenta also significantly increased food intake, body weight gain, and the sizes and number of gastric parietal cells. Conclusion : The results suggest that Cryptolepis sanguinolenta is ulcerogenic, and the gastric secretagogue action is histamine-mediated. This effect could be attributed to the presence of cryptolepine, the major bioactive agent, and other alkaloids present in the botanical. Keywords : Cryptolepis sanguinolenta , body weight, food intake, gastric acid, ulcer

Therapeutic effect of paroxetine on stress-induced gastric lesions in mice

Compared to the well-known anti-ulcerogenic properties of tricyclic antidepressants, the impact of selective serotonin reuptake inhibitors (SSRIs) on gastric mucosa is less clear. Human clinical trials have shown that SSRIs and non-steroidal anti-inflammatory drugs (NSAIDs) act synergistically and promote stomach ulcer formation and upper gastrointestinal tract bleeding. Acute SSRI treatment confers an additional risk for the formation of NSAID-induced gastric ulcers through increase in gastric acid secretion. Stress, which is often experienced by depressed patients, also deteriorates the gastric environment. Thus the potential for exacerbating stress-induced gastric lesions must be considered before prescribing SSRIs. Therefore, we evaluated the effects of paroxetine by using a water-immersion stress-induced stomach ulcer model of mice, by examining single vs. repeated paroxetine treatments for 8 and 22 days before stress induction. Repeated administration of paroxetine significantly decreased the area of stress-induced stomach lesions. Although stress significantly increased the serum corticosterone concentrations, the levels were not affected by the 8-day paroxetine treatment. We confirmed the anxiolytic and antidepressive effects of 8-day paroxetine treatment at 1 and 5 days after stress induction by using the elevated plus-maze and tail-suspension tests. We concluded that repeated paroxetine treatment significantly attenuates the stress-induced ulcerogenic process in the stomach.

Serotonin Reuptake Inhibitor Antidepressants and Abnormal Bleeding

It is generally believed that selective serotonin reuptake inhibitor (SSRI) drugs increase the risk of abnormal bleeding and decrease the risk of ischemic heart disease events by blocking the uptake of serotonin into platelets, leading to an impairment in the platelet hemostatic response. To perform a detailed qualitative review of existing literature on the association of abnormal bleeding with the use of SSRIs. We conducted a PubMed search during June 2009 using the search terms antidepressants and SSRIs (including the names of individual SSRIs: fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, and escitalopram) in association with bleeding, platelets, hemostasis, nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, antiplatelet drugs, proton pump inhibitors, peptic ulcer, premenstrual dysphoric disorder, menstruation, pregnancy, postpartum hemorrhage, surgery, tooth extraction, dental bleeding, stroke, ischemic heart disease, and other terms related to the field. We then searched the reference lists of identified studies. We provide a qualitative discussion of all studies that would inform clinicians about the mechanisms of bleeding and bleeding risks associated with these drugs in different clinical contexts. Epidemiologic studies show that SSRI use is associated with roughly doubled odds of upper gastrointestinal (GI) bleeding; bleeding at other sites has been less commonly described, as has a possibly increased risk of bleeding associated with surgical procedures. The risk of SSRI-associated GI bleeding is increased with the concurrent use of NSAIDs, anticoagulants, and antiplatelet agents and is decreased by concurrent proton pump inhibitors. The risk of bleeding is increased in patients with cirrhosis of the liver or liver failure. There is, curiously, little literature on use of SSRIs and menstrual or postpartum blood loss. Selective serotonin reuptake inhibitors appear protective against ischemic heart disease events. The data are too limited to allow interpretations about influences on ischemic and hemorrhagic stroke. On the basis of the findings of our literature search, we suggest that SSRI-induced increase in gastric acid secretion may explain the GI bleeding risk and that SSRI-related effects on platelet reactivity, endothelial reactivity, and inflammatory markers may explain the ischemic heart disease protective effect. Because the absolute risk of GI bleeds with SSRIs is low, precautions are probably necessary only in high-risk patients, such as those with acid-peptic disease and those with a history of bleeds. We discuss management issues and areas for future research.

The role of cAMP and prostaglandins in gastric acid secretion after pentagastrin administration.

The role of cAMP and prostaglandins as specific intracellular effectors of gastrin action at the level of the parietal cells has not been sufficiently clarified. For this reason we studied the responses of the parietal cells to stimulation with pentagastrin (6 micrograms/kg i.m.) during theophylline infusion (which causes an increase in the intracellular cAMP) and during acetylsalicylic acid infusion (which inhibits the prostaglandin synthesis) in 28 healthy volunteers. Both theophylline and acetylsalicylic acid provoked a significant increase of gastric acid secretion after pentagastrin. Our results suggest that: 1. an increase in intracellular cAMP may be the basis of the stimulatory effect of gastrin on gastric acid secretion 2. a decrease in the synthesis of prostaglandins may lead to a greater gastric acid response after pentagastrin.

Role of gastric acid secretion in the pathogenesis of Barrett's esophageal cancer in a Japanese population.

The acidity of the refluxate into the esophagus is an important factor not only for reflux esophagitis, but also for Barrett's esophagus and the development of Barrett's esophageal cancer. On the other hand, H. pylori infection is thought to prevent reflux esophagitis and Barrett's esophagus by causing atrophic gastritis, which in turn decreases gastric acid secretion. Moreover, the preservation of gastric acid secretion may be important for the development of gastroesophageal junction cancer, including Barrett's esophageal cancer, irrespective of the H. pylori infection status. An increase in gastric acid secretion in Japanese populations has been predicted based on a decreasing rate of H. pylori infection and the westernization of eating habits in Japan; this, in turn, may lead to an increase in the prevalence of Barrett's esophageal cancer in Japan in the future.

Epidemiology and clinical characteristics of GERD in the Japanese population

We reviewed articles on the epidemiology and clinical characteristics of gastroesophageal reflux disease (GERD) in Japan to clarify these features of GERD in this country. Although the definition of GERD depends on the individual study, the prevalence of GERD has been increasing since the end of the 1990s. The reasons for the increase in the prevalence of GERD may be due to increases in gastric acid secretion, a decrease in the Helicobacter pylori infection rate, more attention being paid to GERD, and advances in the concept of GERD. More than half of GERD patients had non-erosive reflux disease, and the majority (87%) of erosive esophagitis was mild type, such as Los Angeles classification grade A and grade B. There were several identified risk factors, such as older age, obesity, and hiatal hernia. In particular, mild gastric atrophy and absence of H. pylori infection influence the characteristics of GERD in the Japanese population. We also discuss GERD in the elderly; asymptomatic GERD; the natural history of GERD; and associations between GERD and peptic ulcer disease and H. pylori eradication. We examined the prevalence of GERD in patients with specific diseases, and found a higher prevalence of GERD, compared with that in the general population, in patients with diabetes mellitus, those with obstructive sleep apnea syndrome, and those with bronchial asthma. We provide a comprehensive review of GERD in the Japanese population and raise several clinical issues.

Gastric secretion elicited by conditioning in rats

Objective. To investigate whether interdigestive gastric acid secretion can be controlled by a possible memory-related cortical mechanism. Material and methods. To evaluate gastric secretion in rats, we used a methodology that allows gastric juice collection in rats in their habitual conditions (without any restraining) by pairing sound as the conditioning stimulus (CS) and food as the unconditioning stimulus (US). The levels of gastric acid secretion under basal conditions and under sound stimulation were recorded and the circulating gastrin levels determined. Results. When the gastric juice was collected in the course of the conditioning procedure, the results showed that under noise stimulation a significant increase in gastric acid secretion occurred after 10 days of conditioning (p<0.01). The significance was definitively demonstrated after 13 days of conditioning (p<0.001). Basal secretions of the conditioned rats reached a significant level after 16 days of conditioning. The levels of noise-stimulated gastric acid secretion were the highest so far described in physiological experiments carried out in rats and there were no significant increases in the circulating gastrin levels. Conclusions. The results point to the important role played by cortical structures in the control of interdigestive gastric acid secretion in rats. If this mechanism is also present in humans, it may be involved in diseases caused by inappropriate gastric acid secretion during the interprandial periods.

Synergistic action of gastrin and ghrelin on gastric acid secretion in rats

Gastrin and ghrelin are secreted from G cells and X/A-like cells in the stomach, respectively, and respective hormones stimulate gastric acid secretion by acting through histamine and the vagus nerve. In this study, we examined the relationship between gastrin, ghrelin and gastric acid secretion in rats. Intravenous (iv) administration of 3 and 10nmol of gastrin induced transient increases of ghrelin levels within 10min in a dose-dependent manner. Double immunostaining for ghrelin and gastrin receptor revealed that a proportion of ghrelin cells possess gastrin receptors. Although (iv) administration of gastrin or ghrelin induced significant gastric acid secretion, simultaneous treatment with both hormones resulted in a synergistic, rather than additive, increase of gastric acid secretion. This synergistic increase was not observed in vagotomized rats.These results suggest that gastrin may directly stimulate ghrelin release from the stomach, and that both hormones may increase gastric acid secretion synergistically.

Gastroprotective action of orexin-A against stress-induced gastric damage is mediated by endogenous prostaglandins, sensory afferent neuropeptides and nitric oxide

Orexin-A, identified in the neurons and endocrine cells in the gut, has been implicated in control of food intake and sleep behavior but little is known about its influence on gastric secretion and mucosal integrity. The effects of orexin-A on gastric secretion and gastric lesions induced in rats by 3.5 h of water immersion and restraint stress (WRS) or 75% ethanol were determined. Orexin-A (5–80 μg/kg i.p.) increased gastric acid secretion and attenuated gastric lesions induced by WRS and this was accompanied by the significant rise in plasma orexin-A, CGRP and gastrin levels, the gastric mucosal blood flow (GBF), luminal NO concentration and an increase in mRNA for CGRP and overexpression of COX-2 protein and the generation of PGE 2 in the gastric mucosa. Orexin-A-induced protection was abolished by selective OX-1 receptor antagonist, vagotomy and attenuated by suppression of COX-1 and COX-2, deactivation of afferent nerves with neurotoxic dose of capsaicin, pretreatment with CCK 2/gastrin antagonist, CGRP 8–37 or capsazepine and by inhibition of NOS with l-NNA. This study shows for the first time that orexin-A exerts a potent protective action on the stomach of rats exposed to non-topical ulcerogens such as WRS or topical noxious agents such as ethanol and these effects depend upon hyperemia mediated by COX-PG and NOS-NO systems, activation of vagal nerves and sensory neuropeptides such as CGRP released from sensory nerves probably triggered by an increase in gastric acid secretion induced by this peptide.

Gastric secretion, proinflammatory cytokines and epidermal growth factor (EGF) in the delayed healing of lingual and gastric ulcerations by testosterone

Hormonal fluctuations are known to predispose ulceration of the upper gastrointestinal tract, but to date no comparative study of their effects on the healing of pre-existing ulcers in the oral cavity and stomach has been made. We studied the effects of depletion of testosterone and of EGF on the healing of acetic acid-induced ulcers using rats having undergone bilateral orchidectomy and/or salivectomy respectively. We measured alterations in gastric acid secretion and blood flow at ulcer margins, as well as plasma levels of testosterone, gastrin and the proinflammatory cytokines IL-1 beta and TNF-alpha. Testosterone (0.01-10 mg/kg/day i. m.) dose-dependently delayed oral and gastric ulcer healing. When applied in an optimal dose of 1 mg/kg/day, this hormone significantly raised gastric acid secretion and plasma IL-1 beta and TNF-alpha levels. Attenuation of plasma testosterone levels via bilateral orchidectomy inhibited gastric acid secretion and accelerated the healing of oral and gastric ulcers, while increasing plasma gastrin levels and these effects were reversed by testosterone. Salivectomy raised plasma testosterone levels, and delayed oral and gastric ulcer healing. Treatment of salivectomised animals with testosterone further inhibited ulcer healing, and this effect was counteracted by EGF. We propose that testosterone delays ulcer healing via a fall in blood flow at the ulcer margin, a rise in plasma levels of IL-1 beta and TNF-alpha and, in the case of gastric ulcers, an increase in gastric acid secretion. EGF released from the salivary glands plays an important role in limitation of the deleterious effects of testosterone on ulcer healing.

Helicobacter pylori

Helicobacter pylori is a common gastric infection that causes serious complications in a minority of individuals. A great deal is known about the disease, but many unanswered questions remain. Among these, perhaps the most enigmatic is that we do not know how the organism is transmitted. We are uncertain why the prevalence of the disease is falling within the developed population. There is still debate as to its relationship with gastroesophageal reflux disease. It is unclear why there are differences in the international incidence of gastric cancer. Similar uncertainties relate to the reasons why the complications of H. pylori infection have changed over time. In this article, I have hypothesized that a number of these unanswered questions may be related to a putative increase in gastric acid secretion that may have taken place during the past 200 years. To date, there is little confirmatory evidence for this, and it remains a fascinating area that merits more scientific research.

Ranitidine reversed the hyperaemic response in the stomach of rats exposed to immobilization stress

The immobilization stress has been recently recognized to produce marked increase of gastric acid secretion and cause hyperaemia in the stomach . Since ranitidine reduced corpus mucosal blood flow in the stomach to basal levels, it may cause suppression of hyperaemia induced by immobilization stress. In this study, 5 groups of 5 rats each were used. The extent of hyperaemia in the glandular mucosa of the stomach of control rats (pretreated with saline) exposed to stress was compared with ranitidine treatment 30 minutes before onset of stress. Gastric hyperaemia elicited in the control rats, while treatment with ranitidine (20 and 40 mg/kg i.m.) 30 minutes before onset of stress, caused a dose – dependent reduction in the gastric hyperaemia response to stress. Furthermore, pretreatment with ranitidine in different doses did not suppress the increase in alanine amino transferase (ALT) activity induced by stress as well as there was no significant difference between plasma cholesterol level in all investigated groups. In conclusion, the present study demonstrates that gastric damage produced by immobilization stress can be protected by ranitidine.