16, 16 dimethyl prostaglandin E2 reduces histamine release from the stomach and protects the gastric mucosal barrier altered by ethanol in neutral solution.

Damage to the gastric mucosal barrier results in histamine release from intramucosal stores. Previous reports have shown that 16, 16 dimethyl prostaglandin E2 (dm PGE2) protects the stomach from injury by various damaging agents in either acidic or neutral solution. Furthermore histamine released in response to a damaging drug in an acidic medium was reduced by dm PGE2. Using the Heidenhain pouch dog preparation, the present study examined the action of dm PGE2 on ethanol-induced barrier breaking and histamine release in neutral solution. Topical ethanol treatment (15% w/v) damaged the gastric mucosal barrier as evidenced by increased net fluxes of Na+ and K+ and an increase in the histamine content of the fluid irrigating the histamine content of the fluid irrigating the Heidenhain pouch. Intravenous injection of dm PGE2 in the doses of 0.01, 0.10 and 1.00 microgram/kg one-half hour before ethanol administration significantly reduced the appearance of Na+, K+ and histamine. It is concluded that dm PGE2 effectively protects the canine gastric mucosa from damaging agents in neutral solution as evidenced by a reduction in the luminal appearance of Na+, K+ and histamine.     

16, 16 Dimethyl prostaglandin E2 reduces histamine release from the stomach and protects the gastric mucosal barrier altered by ethanol in neutral solution

Damage to the gastric mucosal barrier results in histamine release from intramucosal stores. Previous reports have shown that 16, 16 dimethyl prostaglandin E₂ (dm PGE₂) protects the stomach from injury by various damaging agents in either acidic or neutral solution. Furthermore histamine released in response to a damaging drug in an acidic medium was reduced by dm PGE₂. Using the Heidenhain pouch dog preparation, the present study examined the action of dm PGE₂ on ethanol-induced barrier breaking and histamine release in neutral solution. Topical ethanol treatment (15% w/v) damaged the gastric mucosal barrier as evidenced by increased net fluxes of Na+ and K+ and an increase in the histamine content of the fluid irrigating the Heidenhain pouch. Intravenous injection of dm PGE₂ in the doses of 0.01, 0.10 and 1.00 μg/kg one-half hour before ethanol administration significantly reduced the appearance of Na+, K+ and histamine. It is concluded that dm PGE₂ effectively protects the canine gastric mucosa from damaging agents in neutral solution as evidenced by a reduction in the luminal appearance of Na+, K+ and histamine.     

Effect of sialoadenectomy on ethanol-induced gastric mucosal damage in the rat: role of neutrophils

We have observed that removal of the salivary glands is associated with an increase in the susceptibility to gastric mucosal damage in the rat. In the present study, we have examined the effect of sialoadenectomy on ethanol-induced mucosal hemorrhagic damage and myeloperoxidase (MPO) activity. Hemorrhagic damage and MPO activity in response to intragastric 50% w/v ethanol were greater in sialoadenectomized rats when compared with sham-operated animals. Pretreatment with 16,16-dimethylprostaglandin E2 (0.3 micrograms/kg s.c.) reduced damage and MPO activity in both sialoadenectomized and sham control rats receiving 50% ethanol. The reduction in these parameters was greater in control than in sialoadenectomized rats. Pretreatment with epidermal growth factor (5 micrograms/kg s.c.) significantly reduced MPO activity but did not significantly affect the extent of damage. These data suggest that sialoadenectomy is associated with an increase in mucosal inflammation in animals given ethanol. However, in some situations tissue inflammation (as indicated by MPO activity) was reduced, while the proportion of gastric mucosa exhibiting hemorrhagic damage was not changed.     

Mast cell stabilizator and antioxidant effects of epidermal growth factor (EGF) on gastric mucosal injury induced by ethanol in rats

The role of epidermal growth factor (EGF), a polypeptide containing 53 amino acids, on protection and repair of ethanol-induced gastric mucosal injury was investigated in rats. In addition, the effects of EGF on the gastric damage were evaluated histopathologically. We used 48 Spraque-Dawley rats which were divided into [corrected] three groups as control rats, ethanol treated rats and ethanol+EGF treated rats. The ethanol group was given a gastric gavage containing 1 ml of 80% ethanol (v/v) prepared in distilled water. EGF (100 microg/kg) was given by intragastric gavage 30 min before the administration of ethanol. We studied histopathological evaluation and the histochemical heterogeneity of mast cells and its degree of degranulation. Besides, gastric tissue malondialdehyde (MDA), protein sulfhydryl groups (SH), and protein carbonyl levels were measured. EGF treatment stabilized mast cells degranulation and had lower polymorphonuclear leukocytes (PMNL) infiltration, ulcer index, histamine, and MDA; protein carbonyl levels were also lower, compared to the non-treated animals. EGF exerts a protective effect on gastric mucosa to ethanol-induced gastric injury probably through antioxidant and mast cell stabilizing mechanism.     

The effect of sialoadenectomy on gastric mucosal integrity in the rat: roles of epidermal growth factor and prostaglandin E2

Removal of the salivary glands (SALX) in rats has been shown to increase the susceptibility of gastric mucosa to ulcerogens. In the present study, we have investigated the role of specific salivary glands in this response. In addition, we have examined whether a functional link exists between the salivary glands, epidermal growth factor (EGF), and prostaglandin E2 (PGE2) by determining whether SALX decreases the responsiveness of the mucosa to the protective actions of either of both of these agents. Removal of the parotid salivary glands did not significantly increase ulceration in response to intragastric administration of 100% w/v ethanol. Animals were examined 60 min after ethanol administration. Removal of the submandibular-sublingual gland complexes was associated with a significant increase in the area of mucosal damage and a decrease in gastric pit depth in ethanol-treated animals when compared with sham-operated control rats. Furthermore, in both SALX and control animals, exogenous PGE2 and EGF resulted in a dose-dependent reduction in both groups of animals, although the protective effects of PGE2 and EGF were attenuated in SALX rats. PGE2 and EGF administered in combination resulted in the same degree of protection in both SALX and control rats. Sialoadenectomy resulted in a reduction in mucosal PGE2 synthesis. EGF administration did not consistently increase mucosal PGE2 synthesis. Conversely, sialoadenectomy did not reduce mucosal levels of EGF nor did exogenous PGE2 consistently increase salivary or mucosal content of EGF.(ABSTRACT TRUNCATED AT 250 WORDS)     

State of the Na+, K+-ATPase system of the female rat brain cerebral cortex in the postnatal period during ethanol consumption in pregnancy and lactation

The ontogenetic development of the rat brain cortex Na+, K(+)-ATPase and Mg(2+)-ATPase activities under female ethanol (20% v/v) consumption in the third trimester of gestation or in postpartum period was studied. The weight characteristics (body, whole brain and cortex weight) of viable rats on the first day after birth were not affected critically by prenatal alcohol exposure. It is revealed that the delay of postnatal rat growth 10 days after birth under translactational ethanol consumption is accompanied by reliable decrease of plasma membrane Na+, K(+)-ATPase activity in comparison with control animals. The comparable decrease in activities was observed for the ouabain-sensitive and ouabain-resistant Na+, K(+)-ATPase components (isoform species). From the 20th day the differences in enzyme activity were not revealed. Mg(2+)-ATPase increases in postnatal period independent of Na+, K(+)-ATPase activity and it remains insensitive to postnatal maternal alcohol intake. It is suggested, the first ten day period of lactation is critical for ethanol effect on the developmental control of the brain Na+, K(+)-ATPase functional expression and the course of adaptive processes in the rat organism.     

Direct detection of nitric oxide and its roles in maintaining gastric mucosal integrity following ethanol-induced injury in rats

In gastric mucosal injury, nitric oxide (NO) plays both cytoprotective and cytotoxic roles, and the NO level is one determinant of these dual roles. We employed electron paramagnetic resonance (EPR)-spectrometry combined with an NO-trapping technique to directly evaluate NO production in ethanol-induced gastric injury in rats. The rat stomach, mounted on an ex vivo chamber, was perfused with ethanol (12.5 and 43%), and NO levels in mucosal tissues were measured during perfusion. Luminal nitrite/nitrate (NO_x) content, mucosal blood flow, area of mucosal injury, transmucosal potential difference (PD), and luminal pH were simultaneously monitored with/without preadministration of the NO synthase inhibitor, N^G-nitro-L-arginine methyl ester (L-NAME). NO levels in the gastric tissue increased during ethanol perfusion, and luminal NO_x levels increased after the perfusion, accompanying an increase in the area of mucosal injury and changes in physiological parameters. Preadministration of L-NAME aggravated the gastric mucosal damage and suppressed increases in mucosal blood flow in a dose-dependent manner. These results demonstrate that endogenous NO produced in ethanol-induced gastric injury contributes to maintenance of mucosal integrity via regulation of mucosal blood flow.     

Anti-inflammatory agents and substance P depletion in experimental ileitis

To understand the interactions between substance P and gut inflammation, changes in substance P levels were evaluated in a chronic model of ileitis in response to three anti-inflammatory agents with distinct mechanisms of action. The agents were the prostaglandin E(1) analogue misoprostol (30 mug/kg, s.c., b.i.d.), the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mug/ml in drinking water) and the leumedin, N-(fluorenyl-9-methoxycarbonyl)-L-leucine (NPC 15199, 10 mg/kg, s.c.). Ileitis was induced by a transmural injection of trinitrobenzene sulphonic acid (TNBS 30 mg/kg in 50% ethanol) into the distal ileum of guinea-pigs. All anti-inflammatory therapies were introduced after TNBS administration and continued until day 7, when guinea-pigs were killed. Ileal substance P levels were measured by radioimmunoassay, and granulocyte infiltration was quantified by myeloperoxidase (MPO) activity. Protein and nitrite (an index of nitric oxide formation) levels in a luminal saline lavage were quantified in all groups. TNBS ileitis caused a marked reduction in ileal substance P content and increased MPO activity, protein and nitrite secretion. The nitric oxide synthase inhibitor, L-NAME, completely restored all parameters to baseline. Misoprostol attenuated the granulocyte infiltration and exacerbated protein leak but had no effect on substance P levels. In contrast, NPC 15199 had no effect on granulocyte infiltration but normalized substance P levels and protein leak. Only L-NAME and NPC 15199 blocked the TNBS induced increase in nitrite levels. These results suggest that the regulation of granulocyte infiltration in this model is unrelated to changes in substance P levels. Inhibition of nitric oxide synthase was the most effective therapeutic strategy in TNBS ileitis but the precise interactions between nitric oxide and the enteric nervous system during inflammatory states remain to be defined.     

The effect of antimembrane testicular antibodies on Na+, K(+)-ATPase activity in the testicles of rats of different ages]

The effect of large and small doses of rabbit antibodies specific to plasma membranes of the rat testicle cells has been studied in the experiments on Wistar rats of three age groups (preadolescent--aged 20 days, puberal--aged 5-7 months and old--aged 24-26 months). It is stated that incubation of plasma membranes by IgG fraction isolated from antimembrane testicular serum (IgG-ATCSm) in a large dose (43 g of protein G per 125 g of protein of membrane fraction) caused statistically reliable inhibition of Na+, K(+)-ATPase activity in the membranes of testicle cells of puberal and old rats. Preadolescent rats exhibit only a tendency to decrease the activity of this enzyme. Incubation of plasma membranes of testicle cells in rats of different age by small doses of IgG-ATCSm (0.43 g of protein G per 125 g of membrane protein) induced a statistically reliable increase of Na+, K(+)-ATPase activity in puberal and old animals and its slight increase in preadolescent rats. The IgG fraction isolated from normal rabbit serum (IgG-NRS) exerted a less pronounced effect on Na+, K(+)-ATPase activity parallel with retention of a tendency to a decrease of activity under the influence of large doses of the drug and to an increase with introduction of small doses.     

N-acetyl-cysteine: protective agent or promoter of gastric damage?

N-acetyl-cysteine (NAC), when given orally, has been shown to prevent gastric damage induced by ethanol, but when administered intraperitoneally, it appears to potentiate such damage. In an effort to resolve these seemingly discordant findings, fasted rats (six per group) received 1 ml of saline or 20% NAC orally or intraperitoneally (ip). Two hours or 15 min later, they received 1 ml of 100% ethanol orally. At sacrifice 5 min later, rats receiving oral pretreatment with 20% NAC at both 15 and 120 min prior to ethanol exposure demonstrated a significant reduction in the magnitude of gastric injury when compared with saline controls. In contrast, actual promotion of ethanol damage was noted when NAC was given intraperitoneally, but was more pronounced when NAC was administered 15 min prior to exposing the mucosa to 100% ethanol. In all animals receiving intraperitoneal NAC, large amounts of peritoneal fluid (4-6 ml/rat) were recovered at the time of sacrifice, most of which occurred within 15 min of NAC administration; these more pronounced peritoneal effects at 15 min after NAC correlated with the more severe injury from ethanol at this time period compared to 120 min after intraperitoneal NAC. Saline controls had no peritoneal fluid. Mucosal glutathione (GSH) levels generally paralleled these results in that a significant decrease in tissue GSH occurred at 15 min following intraperitoneal NAC when compared with controls; at 120 min after intraperitoneal NAC, GSH levels were similar to control values. Additional experiments demonstrated that within 15 min following NAC administration, systemic blood pressure dropped by approximately 20% and basically remained unchanged over the next 2 hr; intraperitoneal saline had no sustained adverse effects on blood pressure. It was concluded that the inability of NAC to prevent ethanol injury when given intraperitoneally in contrast to orally is related to the drop in blood pressure secondary to NAC's peritoneal irritant effects, which presumably altered gastric mucosal blood flow, thus obivating its ability to prevent ethanol damage under these conditions. Furthermore, the decreased levels in mucosal GSH following the hypotension induced by intraperitoneal NAC suggest that perturbations in GSH metabolism may also have contributed to the decreased resistance to ethanol injury.     

A novel potent inhibitor of inducible nitric oxide inhibitor, ONO-1714, reduces intestinal ischemia-reperfusion injury in rats.

The overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) may contribute to the pathophysiology of intestinal injury induced by ischemia-reperfusion. The aim of the present study was to examine the effect of selective iNOS inhibition by a cyclic amidine analogue, ONO-1714, on reperfusion-induced small intestinal injury and inflammation in rats. Intestinal damage was induced in male Sprague-Dawley rats by clamping both the superior mesenteric artery and the celiac trunk for 30 min, followed by reperfusion. The luminal nitrite concentration in the small intestine was measured by Griess reaction and the iNOS mRNA expression by RT-PCR. The severity of the intestinal mucosal injury and inflammation were evaluated by several biochemical markers and by the histological findings. The rats which were killed after ischemia-reperfusion had increased luminal concentrations of nitrite and iNOS mRNA expression, in addition to severe intestinal inflammation characterized by significant increases in myeloperoxidase activity, a marker of neutrophil infiltration, and by the mucosal content of CINC-1 cytokine, a neutrophil chemotactic cytokine. Administration with ONO-1714 significantly inhibited the luminal NO production. Reperfusion after 30-min ischemia resulted in an increase in luminal protein and hemoglobin concentrations, with levels reaching a maximum after 60 min of reperfusion. In contrast, pre-treatment with ONO-1714 2h before the ischemia inhibited the increases in luminal protein and hemoglobin concentration in a dose-dependent manner (0.001-0.1mg/kg). The contents of the thiobarbituric acid-reactive substances (a marker of oxidative lipid peroxidation) were significantly increased by ischemia-reperfusion, and this increase was reduced by ONO-1714. After reperfusion, the increase in tissue-associated myeloperoxidase activity, an index of neutrophil infiltration, was significantly inhibited by pre-treatment with ONO-1714. ONO-1714 also inhibited increases in intestinal CINC-1 protein and mRNA expression, as determined by ELISA and RT-PCR, respectively. In conclusion, the improvement of reperfusion-induced intestinal injury by ONO-1714 suggested that an excess of NO, produced by iNOS, may have contributed to the initiation/amplification of intestinal inflammatory injury by various mechanisms, including nitrosative and oxidative damage as well as the enhancement of inflammatory cytokine release.     

细胞更新对慢性饮酒大鼠胃黏膜适应性细胞保护的影响

目的: 以低浓度酒精作为弱刺激,通过慢性饮酒的大鼠动物模型,探讨慢性饮酒和大鼠胃粘膜适应性细胞保护作用之间的关系,以及胃粘膜细胞更新的作用.方法: 分别在饮酒不同时程的大鼠胃内灌注2 ml 100%酒精,分析胃粘膜的损伤情况.以流式细胞术、免疫组化和计算机图像处理技术观察大鼠胃粘膜的细胞增殖和凋亡,探讨胃粘膜的细胞更新情况.结果: ①纯酒精可使大鼠的胃体和胃窦出现溃疡和出血,饮用6%(v/v)酒精3～14 d的大鼠这种现象明显减轻,饮用6%(v/v)酒精1 d和28 d的大鼠则无改变.②饮用6%(v/v)酒精3～14 d的大鼠胃粘膜细胞更新加快,而饮酒28 d大鼠胃粘膜细胞凋亡增加,细胞增殖减少.结论: 细胞更新加快是适度低浓度酒精刺激引起的胃粘膜适应性细胞保护作用的重要原因,低浓度酒精刺激超过一定时限可引起胃粘膜萎缩性病变的趋势,使胃粘膜抵抗能力降低.     

Effects of ethanol on gastric acid secretion and gastric mucosal cyclic AMP in the rat.

The effect of ethanol on the secretion of gastric acid and the content of cyclic AMP of the gastric mucosa was studied in rats. Intravenously, ethanol (10 to 800 mg/kg) had no effect on the output of acid. Upon local application into the stomach, ethanol (1 to 10%) caused a concentration-dependent inhibition of the output of gastric acid. The effect was evident within 5 min. At the concentration of 1 %,ethanol decreased the rate of acid secretion maximally by about 30%. At the concentration of 3 %, the maximal inhibition was about 70 %. At the concentration of 10 %, ethanol caused a total cessation of the output of acid within 20 to 60 min.Five and 25 min after the administration of 10 % ethanol into the stomach, the gastric mucosal content of cyclic AMP was decreased by approximately 50 %. Also in vitro, the mucosal content of cyclic AMP was decreased by ethanol within 5 min. The decrease was about 30 % with 2.5 % ethanol, approximately 60 % with 10 % ethanol, and approximately 45 % with 20 % ethanol. Alcohol inhibited the activity of the cyclic AMP phosphodiesterase of the gastric mucosa in a competitive manner. The K_i-value was 0.16 M which would correspond to an alcohol concentration of 9.1 % (v/v). Ethanol caused a concentration-dependent inhibition of the activity of the gastric mucosal adenyl cyclase. By 0.166 M (9.4 %) alcohol the inhibition was nearly 100 %.It is concluded that the ethanol-induced decrease of cyclic AMP in the gastric mucosa is due to a decreased formation of the nucleotide. The accompanying inhibition of the output of acid by ethanol is consistent with the view that cyclic AMP is an intracellular regulator of the gastric acid secretion. In view of the role of cyclic AMP in the control of the integrity of the cells, it is suggested that the ethanol-induced damage of gastric mucosa might also be, at least partly, due to the decreased mucosal content of cyclic AMP.     

Changes in rat gastric proteases with age: effect of hydrocortisone.

Gel filtration on Sephadex G-75 of rat gastric mucosal preparation shows two peaks of proteolytic activity. These peaks differ at different ages of animals. The proteolytic activity of the gastric mucosa is spread over a wider range of pH in younger animals than older ones with a shift from higher pH towards lower pH values with increasing age. Hydrocortisone injection to nine day-old rats results in qualitative changes of gastric mucosal proteases, the proteolytic activity pattern of young treated animals being similar to that of untreated adult rat.     

Effects of Centella asiatica on ethanol induced gastric mucosal lesions in rats

Centella asiatica is a herbal medicine widely used in China and India for wound healing. The aim of this study was to examine its effects on the prevention of ethanol induced gastric lesions in rats. Gastric transmucosal potential difference (PD) was reduced by the application of 50% ethanol in the gastric ex-vivo chamber model and Centella extract (CE) accelerated its recovery. Oral administration of CE (0.05 g/kg, 0.25 g/kg and 0.50 g/kg) before ethanol administration significantly inhibited gastric lesions formation (58% to 82% reduction) and decreased mucosal myeloperoxidase (MPO) activity in a dose dependent manner. These results suggested that CE prevented ethanol induced gastric mucosal lesions by strengthening the mucosal barrier and reducing the damaging effects of free radicals.     

Capsaicin protects against ethanol-induced oxidative injury in the gastric mucosa of rats

In this study, we investigated the protective effects of capsaicin on gastric mucosal oxidative damage induced by ethanol. Sprague Dawley rats intragastrically received 0.5-10 mg/kg, BW capsaicin or vehicle; 30 min later gastric lesions were induced by intragastric administration of absolute ethanol. Lipid peroxidation was estimated by measuring thiobarbituric acid reactive substances in gastric mucosa. Myeloperoxidase activity, a marker enzyme of polymorphonuclear leukocytes for tissue inflammation, was also measured in the gastric mucosa. The expression level of cyclooxygenase-2, which increases in inflammatory region, was determined by Western blot analysis. Capsaicin significantly suppressed gastric haemorrhagic erosions induced by ethanol. Capsaicin inhibited lipid peroxidation and myeloperoxidase activity in ethanol-induced gastric mucosal lesion in a dose-dependent manner. Capsaicin also inhibited the expression of cyclooxygenase-2 in the gastric mucosal lesion. The gastroprotective activity of capsaicin on the ethanol-induced oxidative damage may be important for chemoprevention.     

Capsaicin-sensitive vagal afferents contribute to gastric acid and vascular responses to intracisternal TRH analog

Central injection of TRH or its stable analog, RX77368, produces a vagal cholinergic stimulation of gastric acid secretion, mucosal blood flow and motor function. In the present study, we have investigated the contribution of capsaicin-sensitive vagal afferent fibers to the gastric responses to intracisternal injection of RX77368. Gastric acid secretion, measured in acute gastric fistula rats anesthetized with urethane, in response to intracisternal injection of RX77368 (3-30 ng) was reduced by 21-65% by perineural pretreatment of the vagus nerves with capsaicin 10-20 days before experiments. The increase in gastric mucosal blood flow measured by hydrogen gas clearance induced by intracisternal injection of RX77368 (30 ng) was also reduced by 65% in capsaicin-pretreated rats. In contrast, increases in gastric motor function measured manometrically or release of gastric luminal serotonin in response to intracisternal injection of RX77368 (3-30 ng) were unaltered by capsaicin pretreatment. The mechanism by which vagal afferent fibers contribute to the secretory and blood flow responses to the stable TRH analog is unclear at present, but it is possible that the decrease in gastric mucosal blood flow by lesion of capsaicin-sensitive vagal afferents limits the secretory response.     

Exogenous and endogenous ghrelin in gastroprotection against stress-induced gastric damage

Ghrelin, identified in the gastric mucosa has been involved in control of food intake and growth hormone (GH) release but little is known about its influence on gastric secretion and mucosal integrity. The effects of ghrelin on gastric secretion, plasma gastrin and gastric lesions induced in rats by 75% ethanol or 3.5 h of water immersion and restraint stress (WRS) were determined. Exogenous ghrelin (5, 10, 20, 40 and 80 microg/kg i.p.) increased gastric acid secretion and attenuated gastric lesions induced by ethanol and WRS and this was accompanied by the significant rise in plasma ghrelin level, gastric mucosal blood flow (GBF) and luminal NO concentrations. Ghrelin-induced protection was abolished by vagotomy and attenuated by suppression of COX, deactivation of afferent nerves with neurotoxic dose of capsaicin or CGRP(8-37) and by inhibition of NOS with L-NNA but not influenced by medullectomy and administration of 6-hydroxydopamine. We conclude that ghrelin exerts a potent protective action on the stomach of rats exposed to ethanol and WRS, and these effects depend upon vagal activity, sensory nerves and hyperemia mediated by NOS-NO and COX-PG systems.     

Protective effect of verapamil on gastric hemorrhagic ulcers in severe atherosclerotic rats

Studies concerning with pathogenesis of gastric hemorrhage and mucosal ulceration produced in atherosclerotic rats are lacking. The aim of this study is to examine the role of gastric acid back-diffusion, mast cell histamine release, lipid peroxide (LPO) generation and mucosal microvascular permeability in modulating gastric hemorrhage and ulcer in rats with atherosclerosis induced by coadministration of vitamin D2 and cholesterol. Additionally, the protective effect of verapamil on this ulcer model was evaluated. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vitamin D2 and cholesterol to induce atherosclerosis. Control rats received corn oil only. After gastric surgery, rat stomachs were irrigated for 3 h with either simulated gastric juice or normal saline. Gastric acid back-diffusion, mucosal LPO generation, histamine concentration, microvascular permeability, luminal hemoglobin content and ulcer areas were determined. Elevated atherosclerotic parameters, such as serum calcium, total cholesterol and low-density lipoprotein concentration were obtained in atherosclerotic rats. Severe gastric ulcers accompanied with increased ulcerogenic factors, including gastric acid back-diffusion, histamine release, LPO generation and luminal hemoglobin content were also observed in these rats. Moreover, a positive correlation of histamine to gastric hemorrhage and to ulcer was found in those atherosclerotic rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently ameliorated by daily intragastric verapamil. Atherosclerosis could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine release and microvascular permeability that could be ameliorated by verapamil in rats.     

Effect of acute surgical vagotomy on the mucosal content of 6-keto-PGF1 alpha, PGE2 and glutathione after intragastric 96% ethanol treatment in rats.

It has been observed earlier that gastric cytoprotection produced by PGI2, beta-carotene, small doses of atropine or cimetidine has failed in surgically vagotomized rats. This phenomenon may be in connection with endogenous prostaglandins (PGs) and glutathione (GSH) level of the gastric mucosa. The aims of the study were to evaluate the effect of vagus nerve on the gastric mucosal 6-keto-PGF1 alpha, PGE2 and glutathione after intragastric 96% ethanol (ETOH) treatment. The observations were carried out on CFY rats. The gastric mucosal damage was produced by intragastric administration of 1 ml 96% ETOH. Acute bilateral surgical vagotomy (ASV) was carried out 30 min prior to ETOH application. The animals were sacrificed 1, 5, 15 or 60 min after ETOH installation. The number and the severity of gastric mucosal lesions were noted and 6-keto-PGF1 alpha, PGE2 an GSH contents of gastric mucosa were measured. It has been found that: 1. the number and the severity of gastric mucosal lesions were increased after ASV compared to those with intact vagal nerve, 2. 96% ETOH treatment increased both the gastric mucosal PGs and GSH levels, 3. 6-keto-PGF1 alpha peaked at 5 min PGE2 and GSH peaked at 15 min after ETOH treatment, 4. ASV decreased the gastric mucosal PGs content and delayed the peaks of PGE2 and GSH. It has been concluded that the decreased content of PGs and the delayed GSH increase may play a pathological role in the failure of gastric cytoprotection of rats after ASV.