The role of the vagus nerve in the protective action of acid inhibitors on ethanol-induced gastric mucosal damage in rats

The role of vagus in the actions of different acid inhibitors on ethanol-induced gastric damage and mucosal blood flow (GMBF) changes was studied in anaesthetized rats, using an ex vivo stomach chamber preparation. Subdiaphragmatic bilateral vagotomy decreased the basal gastric acid secretion and GMBF; it also intensified ethanol-evoked lesions in the glandular mucosa. Misoprostol, omeprazole and cimetidine produced a similar degree of reduction in acid output. Misoprostol given subcutaneously (s.c.) (50 micrograms/kg), or added to the incubation solution (12.5 micrograms) for 15 min, markedly prevented ethanol-induced lesion formation and reduction in GMBF. The reversing effect of s.c. injection of misoprostol on either lesion formation or on GMBF reduction was attenuated by vagotomy. Omeprazole protected against lesion formation only when present in the incubation solution (12.5 mg) of ex vivo chamber preparations of both vagus-intact and vagotomized animals, but the effect was significantly less in the latter group. The drug also prevented the depressive action of ethanol in vagus-intact animals. Cimetidine pretreatment (50 mg s.c. or 12.5 mg in incubation solution), however, did not modify the effects of ethanol on lesion formation and the GMBF. The findings indicate that the three different types of acid inhibitors exert different actions on ethanol-induced gastric mucosal damage, although they produced similar inhibition of acid output. Vagotomy lowers the GMBF and attenuates the antiulcer action of misoprostol and omeprazole, especially when the drugs are given by the parenteral route.     

The influence of acute or chronic nicotine treatment on ethanol-induced gastric mucosal damage in rats

The influences of acute or chronic nicotine pretreatment on ethanol-induced changes on gastric secretion, mucosal blood flow (GMBF), and glandular mucosal damage were studied in anesthetized rats. Ethanol administration decreased gastric acid secretion and GMBF, which were accompanied by a marked increase in gastric mucosal damage. Acute nicotine incubation 2 or 4 mg dose-dependently elevated both the titratable acid in the luminal solution and the gastric secretory volume; it also prevented the depressive action on GMBF and gastric mucosal damage in ethanol-treated animals. Chronic nicotine treatment for 10 days reduced the inhibitory action of ethanol on gastric acid secretion; the higher dose (25 micrograms/ml drinking water) potentiated the decrease of GMBF and the ulcerogenic property of ethanol. However, chronic treatment with the lower dose (5 micrograms/ml drinking water) had the opposite effects; it also markedly increased the gastric secretory volume. It is concluded that acute nicotine pretreatment elevates, whereas chronic nicotine pretreatment differentially affects GMBF. These effects could account for their protective or preventive actions on ethanol ulceration. The increase in nonacid gastric secretory volume by nicotine could partially explain its antiulcer effect. Furthermore, the acid secretory state of the stomach appears unrelated to the ulcerogenic property of ethanol.     

Time course study on the action of 5-hydroxytryptamine on gastric secretion and mucosal blood flow and on ethanol-induced gastric mucosal damage in rats.

The effects of 5-hydroxytryptamine (5-HT; given i.p. in doses of 1 or 10 mg/kg) on gastric secretion and mucosal blood flow (GMBF) and on ethanol-induced gastric mucosal damage were studied in rats over a period of 30-450 min. The blood pressure was also examined, in relation to the changes in GMBF. 5-HT, 10 mg/kg, given 30 min before ethanol administration markedly worsened lesion formation and this potentiating action was present for a further 90 min; a significant protective effect was seen only at 450 min after 5-HT injection. The lower dose of 5-HT, 1 mg/kg, did not affect the severity of gastric damage. 5-HT (10 mg/kg) also decreased GMBF at 30 min after injection and this lasted up to the end of 120 min, but the depressive action of ethanol on GMBF was reversed at 450 min. The basal gastric secretory volume was depressed from 30 to 120 min but acid output fell from 75 to 120 min after the higher dose of 5-HT; this reduction of acid secretion was followed by an increase from 360 to 450 min. 5-HT decreased the mean blood pressure in a dose- and time-dependent manner. The heart rate was unaffected by either dose level of 5-HT. The present study not only demonstrates the ulcerogenic action of 5-HT but also the protective nature of the amine. The reduction in secretory volume and lesion formation, but not acid secretion, seems to be related to GMBF depression, whereas the protective action depends on the maintenance of GMBF.     

Monochloramine impairs mucosal blood flow response and healing of gastric lesions in rats: relation to capsaicin-sensitive sensory neurons

AIMS:We examined the effects of monochloramine (NH2Cl) on the gastric mucosal blood flow (GMBF) response and the healing of ethanol-induced gastric lesions in rats. METHODS: Rats fasted for 18 h were given the 99% ethanol p.o. for induction of gastric lesions, and were fed normally from 1 h later onwards. Monochloramine, at non-ulcerogenic doses (5 to approximately 20 mmol/L), was given p.o. twice daily for 7 days, starting 2 h after ethanol treatment. RESULTS: Gastric lesions caused by ethanol healed almost completely within 7 days with re-epithelialization. The repeated administration of NH2Cl significantly delayed the healing of ethanol-induced gastric lesions in a dose-dependent manner. The damaged mucosa showed a marked rise in H+ permeability, resulting in luminal acid loss, but this process was accompanied by an increase of mucosal blood flow. Monochloramine did not affect the increased mucosal H+ permeability observed in the stomach after damage by ethanol, but significantly inhibited the mucosal hyperemic response associated with luminal acid loss. Prior exposure of the mucosa to NH2Cl (20 mmol/L) did not affect the gastric hyperemic response caused by mucosal application of misoprostol (a prostaglandin E1 derivative) or NOR-3 (a nitric oxide donor), but totally attenuated the increase of GMBF in response to intragastric capsaicin. Impaired healing and GMBF responses were also observed in rats following chemical ablation of capsaicin-sensitive sensory neurons. CONCLUSIONS: These results suggest that NH2Cl impaired the healing of acute gastric mucosal lesions at low concentrations, and this action may be attributable, at least partly, to the impairment of gastric hyperemic response caused by the dysfunction of capsaicin-sensitive sensory neurons.     

Portal hypertension

The time-course effects of portal hypertension on gastric secretory function, mucosal blood flow, vascular permeability, and ethanol-induced gastric mucosal damage were examined in anesthetized rats. Partial ligation of the portal vein effectively produced portal hypertension one to three days later but the raised pressure returned to normal on the sixth day after ligation. This time-course effect coincided with reduced pepsin secretion and mucosal blood flow and also with potentiated ethanol-induced mucosal damage during the first to third days. These effects started to tail off on the sixth day. However, gastric acid output was significantly reduced on the third day, and this was strongest on the sixth day after operation. Portal vein ligation also reduced basal vascular permeability, which was markedly potentiated after ethanol treatment. It is concluded that: (1) portal vein blood pressure changes are a time-dependent process following ligation; (2) changes in gastric mucosal blood flow (GMBF) and lesion formation are closely related to portal hypertension; (3) gastric mucosal injury is associated with vascular damage, as evidenced by increased in vascular permeability; and (4) pepsin but not acid secretion is closely related to the state of the GMBF.     

Modulatory action of adenosine on gastric function and ethanol-induced mucosal damage in rats

This study examines the gastric effects of adenosine and its antagonist, theophylline, on secretory function, mucosal blood flow, and on ethanol-induced glandular mucosal damage in rats that were fasted for 24 hr before experimentation. The animals were anesthetized with sodium pentobarbitone (50 mg/kg intraperitoneal) and their tracheae cannulated. An ex vivo stomach chamber then was prepared. The luminal bathing solution was collected every 15 min and the concentrations of H⁺ and Na⁺ were determined by a pH autotitrator and an ionmeter, respectively. The glandular mucosal blood flow was measured by a laser Doppler flowmeter and the severity of lesions was determined by measuring the hemorrhagic areas. Adenosine administration (2.5 or 7.5 mg/kg, subcutaneous) markedly lowered the H⁺ and Na⁺ output but increased the secretory volume and mucosal blood flow in a dose-dependent manner. The same doses of the nucleoside also prevented ethanol-induced mucosal damage. These effects were prevented by pretreatment with theophylline (30 or 60 mg/kg, subcutaneous). Ethanol given alone significantly depressed the H⁺ and Na⁺ secretion. Both effects were not modified by adenosine treatment. However, the depressive action of ethanol on mucosal blood flow was prevented by adenosine. These findings indicate that adenosine modulates the physiological function of the stomach. It also directly activates the defensive mechanism of the stomach, which is partially mediated by the improvement of the gastric mucosal blood flow and an increase in the nonacid component of gastric secretion.     

Nitric oxide-mediated gastric hyperemia decreases ethanol-induced gastric mucosal injury in uremic rats

We investigated whether the recently described endothelium-derived nitric oxide-mediated gastric hyperemia in the uremic rat protects the gastric mucosa against ethanol injury. Uremia was induced by subtotal nephrectomy. Basal gastric mucosal blood flow, measured by a hydrogen gas clearance technique, was significantly higher in uremic than control rats. Continuous intragastric perfusion with 40% ethanol produced significantly less gross and histological lesions in uremic than in control rats. The administration of 3 mg/kg ofN ^W-nitro-l-arginine methyl ester, a specific inhibitor of nitric oxide biosynthesis, decreased resting gastric mucosal blood flow to control levels in uremic rats, but had no effect on basal gastric blood flow in control rats. This pretreatment with the inhibitor of nitric oxide biosynthesis increased 40% ethanol-induced gastric mucosal lesions in uremic rats to the same level as that observed in control rats, but had no effect on lesions in control rats. In conclusion, this study suggests that in the uremic rat, gastric hyperemia, mediated by increased endothelium-derived nitric oxide, attenuates ethanol-induced gastric mucosal injury.Dr. Enrique Quintero is the recipient of a Fogarty International Fellowship Award (N.I.H.) (1 FO5 TW04443-01) and a Grant from Consejería de Educación, Cultura y Deportes of the Canary Islands Autonomous Government. This work was also supported by Veterans Administration Research Funds.     

The role of serotonin in ethanol-induced gastric glandular damage in rats

The effects of serotonin (5-HT) or methysergide (a 5-HT antagonist), given intraperitoneally 30 min beforehand, on ethanol-induced mucosal injury and mucosal blood flow were studied in rats. 5-HT itself dose dependently decreased the gastric mucosal mucus content and induced gastric damage in conscious animals. It also worsened ethanol-induced lesion formation but not mucus depletion. Methysergide pretreatment only prevented the former action. In the ex vivo chamber preparation, 5-HT lowered the gastric mucosal blood flow and produced mucosal damage in unconscious animals. It also potentiated ethanol-induced gastric injury and 5-HT release. Methysergide significantly prevented lesion formation and 5-HT release in ethanol-treated rats. Ethanol decreased the gastric mucosal blood flow in the mucosa which had been preincubated with HCl. This depression of gastric mucosal blood flow was further reduced by 5-HT, but was reversed by methysergide. The lesion-potentiating or -protecting actions of 5-HT or methysergide, respectively, suggest that the amine is involved in gastric mucosal damage by ethanol in rats.     

Role of mucosal microcirculation in gastric lesions induced by lateral hypothalamic lesions in rats

To evaluate the pathophysiology underlying gastric mucosal lesions induced by lateral hypothalamic (LH) lesions, we investigated the changes in acid secretion, gastric mucosal blood flow, gastric mucus and mucosal integrity in the corpus during the 4 h period and 48 h after the production of bilateral electrolytic LH lesions in male Sprague-Dawley rats. Gastric mucosal lesions were macroscopically produced 24 h (63%) and 48 h (83%) after LH lesions, although there were no visible lesions at 7 h. Gastric acid secretion was significantly increased 48 h after LH lesions, compared with that in the control group. Gastric mucosal blood flow and transmucosal potential difference (PD) in the LH lesion group immediately decreased after LH lesions and did not recover during 4 h and at 48 h. On the contrary, in the control group, gastric mucosal blood flow decreased after the brain surgery but soon recovered, and there was no significant change in PD. LH lesions resulted in the reduction of intramucosal mucus to 50% 3 h after LH lesions. Moreover, we exposed the stomach to 10 mmol/L taurocholic acid (TCA) 3 h after LH lesions to examine the disruption in gastric mucosal defensive function in rats with LH lesions. The recovery of the reduced PD by TCA was slow and gastric mucosal lesions were easily formed in the LH lesion group. These results suggest that gastric mucosal ischaemia after lesioning of LH immediately results in the disruption of mucosal defensive function before the formation of visible gastric lesions, and predisposes to the formation of gastric mucosal lesions by a delayed increase in acid secretion.     

Role of endogenous endothelin-1 in ethanol-induced gastric mucosal damage in humans

Gastric microcirculatory disturbances are involved in the ethanol-induced gastric mucosal damage. In this study in humans we evaluated the time course of plasma and gastric mucosal endothelin-1 (ET-1) concentrations after intragastric ethanol administration; furthermore we determined the correlation among changes in gastric tissue endothelin-1 and microscopic and gross gastric hemorrhagic damage. ET-1 concentrations in plasma and gastric mucosa were measured by radioimmunoassay. The endoscopic appearance of the gastric mucosa was evaluated and scored on a scale of 0–5, and gastric biopsies for histological evaluation were obtained from the antral and the corpus mucosa just before and 30 min after 40% ethanol administration in seven healthy volunteers. Plasma ET-1 concentration increased as soon as 20 min after ethanol administration, reached a significant peak at 30 min (P < 0.01), and returned to near basal level within 120 min. Gastric mucosal ET-1 concentration significantly increased 30 min after ethanol administration in both the body (P < 0.05) and the antrum (P < 0.05) of the stomach; however the ET-1 increase was significantly higher in the body. Moreover, data obtained 30 min after ethanol administration showed a significant correlation between gastric mucosal ET-1 levels and gross hemorrhagic damage (r = 0.84). A significant correlation was also observed between antral gastric mucosal ET-1 and microscopic lesions (r = 0.70). We conclude that 40% ethanol, given orally, stimulates the release of gastric mucosalendothelin-1 and causes a rapid and time-dependent increase of ET-1 plasma level in humans. The increased plasma and gastric tissue endothelin-1 concentration may play a role in ethanol-induced gastric hemorrhagic injury in humans.     

Effects of chronic normovolemic anemia on gastric microcirculation and ethanol-induced gastric damage in rats

The effects of chronic normovolemic anemia on gastric microcirculation and gastric mucosal susceptibility to ethanol-induced gastric damage were investigated in anesthetized rats. Blood exchange by a plasma expander during four consecutive days rendered the animals anemic with a 34% decrease in the baseline hematocrit but without affecting blood volume. Chronic anemia induced a decrease in whole blood viscosity, an increase in gastric mucosal blood flow measured by hydrogen gas clearance, a decrease in gastric vascular resistance, and a decrease in gastric hemoglobin content without changes in the gastric oxygen content, the latter two parameters being measured by reflectance spectrophotometry. Gastric mucosal blood flow was lowered by intragastric administration of 100% ethanol in both anemic and control rats, but the final blood flow was significantly higher in anemic than in control animals. Macroscopic gastric damage induced by ethanol administration was significantly lower in anemic than in control rats. We conclude that chronic normovolemic anemia increases gastric mucosal blood flow and leads a protecting mechanism against gastric mucosal damage induced by absolute ethanol.     

血管活性肠肽参与电针对大鼠胃粘膜损伤的保护作用

目的：探讨血管活性肠肽(VIP)参与电针对胃粘膜损伤大鼠保护作用的机制。方法：采用束缚冷应激胃粘膜损伤大鼠模型，通过放射免疫测定法和中枢迷走背核复合体(DVC)微量注射，观察电针对各组外周血、胃粘膜和脑组织的VIP含量的变化，胃粘膜血流量(GMBF)、损伤指数(LI)和跨壁电位差(PD)的影响。结果：电针模型组外周血、胃粘膜和脑组织VIP含量均增加，GMBF、PD也明显增加，LI下降；中枢DVC微量注射VIP后，外周血和胃粘膜中VIP含量增加。结论：VIP作为信号分子，通过神经内分泌免疫网络系统对胃粘膜损伤具有整体调控作用。     

Intracisternal thyrotropin-releasing hormone-induced vagally mediated gastric protection against ethanol lesions: Central and peripheral mechanisms

Abstract The vagus is involved in mediating gastric cytoprotection and adaptive cytoprotection. However, the central and peripheral mechanisms through which the vagus expresses its action are still poorly known. Medullary thyrotropin-releasing hormone (TRH) plays an important role in the vagal regulation of gastric function. The stable TRH analogue, RX 77368, micro-injected into the cisterna magna or the dorsal motor nucleus (DMN) of the vagus at a dose that did not influence gastric acid secretion prevented gastric injury induced by intragastric administration of 60% ethanol in conscious or urethane-anaesthetized rats. The cytoprotective action of TRH is mediated through vagal cholinergic release of prostaglandin E₂ (PGE₂). Prostaglandin E₂ action is unrelated to changes in gastric mucosal blood flow (GMBF). In addition, other peripheral mechanisms involve calcitonin gene-related peptide (CGRP) contained in capsaicin sensitive afferent fibres and nitric oxide, both of which mediate the associated increase in GMBF induced by intracisternal injection of RX 77368. These data indicate that medullary TRH induces vagally mediated gastric protection against ethanol lesions. Its action is expressed through the muscarinic dependent release of PGE₂ and nitric oxide, and efferent function of capsaicin-sensitive afferent fibres releasing CGRP.     

Mechanism of intragastric nicotine protection against ethanol-induced gastric injury

To elucidate the mechanism of intragastric nicotine protection against ethanol-induced gastric mucosal injury seen in a previous report and in our preliminary study, the following studies were performed. Rats were pretreated with naloxone (8 mg/kg intraperitoneal, 0.5 hr prior to study) to block opiate receptors; or capsaicin (125 mg/kg subcutaneous 10 days prior to study) to denervate the afferent sensory fibers; or indomethacin (2.5 mg/kg intragastric or 5 mg/kg subcutaneous, 1 hr prior to study) to inhibit endogenous prostaglandin synthesis. At 1-hr intervals, nicotine (4 mg/kg) or vehicle and 40% ethanol were then given intragastrically. Total gastric corpus mucosal lesion length was measured unbiasedly. In separate studies, gastric mucosal blood flow (GMBF) was assessed by hydrogen gas clearance before and after intragastric nicotine or vehicle; luminal mucus volume, gastric juice volume, and acid output were measured 1 hr after either intragastric nicotine or vehicle administration. The results showed that the acute protective effect of intragastric nicotine was associated with a significantly larger luminal mucus volume. It was not blocked by naloxone, capsaicin, or indomethacin. There was no increase in GMBF. The larger gastric residual volume did not account for the protection. We conclude that the mechanism mediating nicotine protection is unique and is independent of opiate receptors, capsaicin-sensitife afferent sensory nerve fibers, endogenous prostaglandin generation, or dilution of the injurious agent. The increase in luminal gastric mucus volume may contribute to the protective effect of intragastric nicotine against gastric mucosal injury produced by 40% ethanol.     

Reversal of the gastric effects of nicotine by nitric oxide donor treatment

Nicotine intensifies experimental gastric ulceration by reducing gastric mucosal blood flow (GMBF) and mucus. As both these parameters can be improved by nitric oxide (NO), we evaluated the impact of a NO donor in ethanol-induced gastric mucosal injury in rats administered nicotine. A nicotine solution or water was administered for 20 days to Sprague-Dawley rats. NO donor (isosorbide dinitrate) was given 60 and 10 min before preparation of ex vivo gastric chambers and exposure to ethanol. Chronic nicotine intake significantly reduced GMBF and gastric mucus content. Nicotine intensifies ethanol-induced gastric injury and short-term administration of NO donor failed to antagonize the ulcerogenic action from either nicotine or alcohol. In another study, rats drank nicotine solution for 20 days, after which the nicotine was withdrawn and replaced by water for 10 additional days. NO donor was provided during these last 10 days. The gastric effects of nicotine persisted for at least 10 days after nicotine was withdrawn but then these effects could be abolished by prolonged NO treatment. Nicotine reduces plasma nitrite level, but gastric mucosal MPO activity remained unchanged. Our data suggest that nicotine cessation plus a longer period of NO donor administration can completely abolish the gastric effects of nicotine.     

Probable role of both sulfhydryls and prostaglandins in gastric mucosal protection induced by S-adenosylmethionine

The role of both sulfhydryl groups and endogenous prostaglandins in the protective effect of S-adenosylmethionine against ethanol-induced gastric mucosal damage was studied in rats. Drugs were administered subcutaneously or intragastrically to fasted rats 30 or 60 min before 100% ethanol (1 ml/rat), and mucosal lesions were measured planimetrically 1 h later. The gastric mucosal protection given by S-adenosylmethionine or by 20% ethanol (adaptive protection) was significantly diminished by pretreatment of rats with the sulfhydryl blocker iodoacetamide or with the cyclooxygenase inhibitor indomethacin. The protective effect of S-adenosylmethionine could be totally abolished only by pretreatment with the combination of iodoacetamide and indomethacin. Our present data suggest that endogenous release of prostaglandins and sulfhydryl groups may play a role in the protective actions of both S-adenosylmethionine and 20% ethanol (adaptive protection) against ethanol-induced gastric mucosal damage.     

Influence of NG‐nitro‐L‐arginine methyl ester and L‐arginine on gastric mucosal tolerant cytoprotection under stress

OBJECTIVE : To determine the role of endogenous nitric oxide (NO) in gastric mucosal tolerant cytoprotection under stress and its possible mechanism. METHODS : Sprague–Dawley rats were exposed to repeated water immersion and restraint stress (WRS), during which N^G‐nitro‐L ‐arginine methyl ester (L ‐NAME), a non‐selective NO synthase inhibitor, and L ‐arginine (L ‐Arg), a substrate for NO synthesis, were administered to inhibit or promote the synthesis of endogenous NO, respectively. Gastric mucosal blood flow (GMBF) was measured with an LDF‐3 Flowmeter (Electronic Instrument Factory of Nankai University, Tianjin, China), the NO level in the gastric mucosa was monitored by the Griess reaction and gastric mucosal lesions were evaluated using the ulcer index (UI). The relationships between changes in GMBF, UI and NO content in the gastric mucosa were analyzed by linear correlation analysis. RESULTS : Repeated WRS induced gastric mucosal tolerant cytoprotection and this was accompanied by increased GMBF and NO levels in the gastric mucosa. Inhibition of endogenous NO synthesis by L ‐NAME worsened mucosal lesions induced by single WRS and, after repeated WRS, the adaptive incremence in GMBF was abolished and the NO content in the gastric mucosa was significantly reduced. In contrast, enhancement of endogenous NO synthesis by L ‐Arg attenuated mucosal erosions caused by single WRS. After repeated WRS, GMBF and the NO content in the mucosa increased gradually. Mucosal lesions were negligible after rats were exposed to the fourth WRS. CONCLUSIONS : During the tolerant cytoprotection, GMBF, UI and the NO content showed regular changes and there were good relationships between them. L ‐NAME and L ‐Arg changed the levels of endogenous NO, which, accordingly, affected GMBF and the gastric tolerance. By regulating GMBF, endogenous NO may play an important role in the gastric mucosal tolerant cytoprotection under stress. Inhibition of the synthesis of NO delayed the induction of tolerant cytoprotection, whereas increased NO synthesis promoted cytoprotection.     

Gastric mucosal blood flow in rats after administration of 16,16-dimethyl prostaglandin E2 at a cytoprotective dose

The purpose of the present study was to determine whether the gastric cytoprotective effect of a prostaglandin such as 16,16-dimethyl prostaglandin (dmPGE2) is mediated by an increase in mucosal blood flow. Gastric mucosal blood flow was measured in urethane-anesthetized rats by the hydrogen gas clearance technique. In control rats given no ethanol, intragastric administration of dmPGE2 (10 micrograms/kg body wt) produced a significant reduction (15.3%) in gastric mucosal blood flow 30 min after treatment. This dose of dmPGE2 significantly reduced the formation of the gross gastric lesions produced by absolute ethanol in anesthetized rats. In vehicle-pretreated animals, blood flow was invariably absent in the ethanol-induced mucosal lesion areas. In the nonlesion areas, gastric mucosal blood flow was the same in prostaglandin-pretreated and vehicle-pretreated animals as in control (no ethanol) rats. Thus, although dmPGE2 pretreatment protected against ethanol-induced gastric mucosal injury and prevented the accompanying blood flow stasis, it did not do this by an increase in gastric mucosal blood flow. The protection also is not due to a decrease in flow because, in separate groups of anesthetized rats, a 15% reduction in gastric mucosal blood flow induced by either hemorrhage or intravenous vasopressin did not protect the gastric mucosa against absolute ethanol-induced injury. Whether the maintenance of gastric mucosal blood flow is a primary or secondary effect of prostaglandin cytoprotection remains to be determined.     

The role of gastric mucosal histamine in acid secretion and experimentally induced lesions in the rat

The role played by histamine from enterochromaffin-like (ECL) cells and mast cells in gastric acid secretion and in the development of ethanol-induced gastric lesions was studied in the rat. This was done by examining the effects of inhibition of the histamine-producing enzyme histidine decarboxylase (HDC) with alpha-fluoromethylhistidine (alpha-FMH) and the effects of degranulation of the mucosal mast cells with dexamethasone. A single dose of alpha-FMH (50 mg/kg p.o.) inhibited the HDC activity by 94% but did not affect histamine levels in the gastric mucosa 2 h after dose. Repeated treatment resulted in an almost complete inhibition of HDC activity and in a reduction of histamine levels by 75%. Pentagastrin failed to stimulate acid secretion after 4 days treatment with alpha-FMH, whereas the acid response to histamine was unaffected in chronic gastric fistula rats. Ethanol failed to induce gastric lesions in rats pretreated for 4 days with dexamethasone whereas 4 days pretreatment with alpha-FMH did not influence ethanol-induced lesion formation. The present results show that histamine synthesis is required for pentagastrin-stimulated gastric acid secretion and that mucosal mast-cell histamine plays a role in the development of ethanol-induced gastric lesions.     

Effect of glutathione on gastric mucosal lesion induced by restraint water-immersion in rats

AIM To determine the effect of glutathione (GSH) on stress gastric mucosal lesion.METHODS The stress gastric mucosal lesion as produced by restraint water-immersion in rats and gastricmucosal lesion, gastric mucosal GSH content, gastric acid secretion and gastric barrier mucus secretion wereexamined. We also observed the effect of GSH on gastric mucosal lesion and the effect of N-ethylmaleimine(NEM) and indomethacin on GSH protection. Comparisons between two groups were made using the Students t test.RESULTS GSH (100 and 200 mg/kg) intraperitoneally protected against stress gastric mucosal lesion(P<0.001 and P<0.001). Restraint water-immersion stress significantly reduced gastric mucosal GSHcontent (P < 0.001), but pretreatment with GSH (100 mg/kg) had no effect on gastric mucosal GSH content(P>0.05). The preinjection of NEM (10 mg/kg, sc.), a sulfhydryl-blocking reagent, or indomethacin(5 mg/kg, im.), a cyclooxygenase inhibitor, had no effect on protection of GSH (P>0.05). GSH(100mg/kg) significantly increased secretion of gastric barrier mucus (P<0.05), but had no effect onsecretion of gastric acid in restraint water-immersed rats (P >0.05).CONCLUSION GSH can inhibit the formation of gastric mucosal lesions induced by restraint water-immersion. The protective effect of GSH was due, in part, to promoting the secretion of gastric barriermucus, but not to suppress the gastric acid secretion. The protection effect of GSH has no relation withgastric mucosal GSH and PGs.