The effect of prostacyclin on gastric mucosal protein, DNA and RNA content, with special reference to different ulcer models

The effect of prostacyclin on gastric mucosal protein, DNA and RNA content has been investigated, either administered alone or in the course of indomethacin and stress-induced experimental ulcer models. It seems that: The oral administration of 100 micrograms/kg prostacyclin caused a prevailing DNA increase (decrease of the RNA/DNA ratio) in the rat gastric mucosa. Indomethacin and stress (restraint) ulcer formation were also followed by a predominant mucosal DNA increase which was maintained even during PGI2 treatment. The observed changes in RNA/DNA ratios were interpreted as a sign of accelerated cell renewal.     

Circadian Reactivity Rhythm of Rat Gastric Mucosa to Restraint-Cold Stress and Indomethacin: Temporal Variation in the Protective Effect of Iloprost

In this study, the time-dependent ulcerogenic effects of restraint-cold stress and indomethacin on the gastric mucosa and the temporal variation in the protective effect of iloprost, a synthetic stable analog of prostacyclin, were investigated in rats synchronized to 12h light and 12h darkness, lights on at 08:00. The severity of gastric ulceration produced by either stress or indomethacin showed marked circadian variation; it was greatest at 11 HALO (hours after lights on) for restraint-cold stress and at 23 HALO for indomethacin. The severity of the induced ulcerogenesis was least at 7 HALO for both stimuli. The protective effect of iloprost against restraint-cold stress was most prominent at 15 HALO and 19 HALO with an approximately 80% protection score. On the other hand, pretreatment with iloprost reduced the indomethacin-induced mucosal injury only at 23 HALO. The circadian variation in the effect of iloprost and in the rhythmic modalities of these two experimental ulcer models are indicative of differences in their underlying mechanisms. In experimental models of ulceration, the circadian time of application of the ulcerogenic stimulus must be considered as an important experimental factor. Moreover, the protective effectiveness of antiulcer drugs can express time-dependent differences and must also be taken into account in investigative research. (Chronobiology International, 14(6), 575–583, 1997)     

Effect of indomethacin, tiaprofenic acid and dicrofenac on rat gastric mucosal damage and content of prostacyclin and prostaglandin E2

Gastric ulcerogenicity and depletion of endogenous prostaglandins (PGs) content induced by tiaprofenic acid, dicrofenac and indomethacin were examined using the same antiinflammatory effective doses. Male Wistar rats were given each of these drugs intragastrically 24, 18, and 3 hrs before sacrifice in the following doses (mg/kg): indomethacin (0.8, 4 and 20); tiaprofenic acid (1.2, 6 and 30); dicrofenac (0.8, 4 and 20). Endogenous prostacyclin (PGI2) and PGE2 in fundic mucosa were determined by radioimmunoassay. The three compounds produced fundic mucosal lesions in a dose-dependent manner. However, tiaprofenic acid and dicrofenac were both less potent than indomethacin in producing gastric mucosal lesions at similar antiinflammatory doses. Mucosal PGE2 content was abolished by the three compounds in the following doses (mg/kg): indomethacin (4 and 20); tiaprofenic acid (6 and 30); dicrofenac (20). Mucosal PGI2 was maintained around 50% of the control value in rats given tiaprofenic acid in a dose of 6 mg/kg or dicrofenac in a dose of 4 mg/kg, while indomethacin in a dose of 4 mg/kg markedly reduced mucosal PGI2 to 17% of the control value. In larger doses, tiaprofenic acid and dicrofenac were also significantly less potent in reducing mucosal PGI2 than indomethacin. These results suggest that the difference in ulcerogenicity between indomethacin and the other two compounds was closely related to their potency in decreasing PGI2 in the gastric (fundic) mucosa.     

Vagal nerve and the gastric mucosal defense

An essential role for an intact vagal nerve has been proven in the development of gastric mucosal cyto- and general protection. On the other hand, chemically-induced (ethanol, HCl, indomethacin) gastric mucosal damage is enhanced after acute surgical vagotomy. The aims of this paper were to study the possible mechanisms of the vagal nerve in the development of gastric mucosal defense. The following questions were addressed: 1) effect of surgical vagotomy on the development of ethanol- (ETOH), HCl-, and indomethacin (IND)-induced gastric mucosal damage; 2) changes in the gastric mucosal defense by scavengers, prostacyclin and other compounds (small doses of atropine and cimetidine: 3) changes in the gastric mucosal vascular permeability due to chemicals; 4) effect of indomethacin in the ETOH and HCl models with and without surgical vagotomy; 5) changes in the gastric mucosal content of prostacyclin and PGE₂ in the ETOH and HCl models after surgical vagotomy; and 6) changes in the role of SH-groups in gastric mucosal defense after surgical vagotomy. It was found that: 1) the gastric mucosal damage produced by chemicals (ETOH, HCl, and indomethacin) was enhanced after surgical vagotomy; 2) the cyto- and general gastric protective effects of β-carotene, prostacyclin, and small doses of atropine and cimetidine disappeared after surgical vagotomy; 3) the vascular permeability due to chemicals (ETOH, HCl, indomethacin) significantly increased after surgical vagotomy in association with an increase in both number and severity of gastric mucosal lesions; 4) IND alone (in animals with an intact vagus) did not produce gastric mucosal lesions (in 1-h experiments), but it aggravated ETOH-induced gastric mucosal damage (both its number and severity); 5) the gastric mucosal levels of prostacyclin and PGE₂ decreased after surgical vagotomy; 6) IND application (after surgical vagotomy) decreased further the tissue levels of prostacyclin and PGE₂ in association with an increase of gastric mucosal damage; and 7) the gastric mucosal protective effects of SH-groups were abolished by surgical vagotomy.     

Effect of indomethacin, tiaprofenic acid and dicrofenac on rat gastric mucosal damage and content of prostacyclin and prostaglandin E2

Gastric ulcerogenicity and depletion of endogenous prostaglandins (PGs) content induced by tiaprofenic acid, dicrofenac and indomethacin were examined using the same antiinflammatory effective doses. Male Wistar rats were given each of these drugs intragasrically 24, 18, and 3 hrs before sacrifice in the following doses (mg/kg): indomethacin (0.8, 4 and 20); tiaprofenic acid (1.2, 6 and 30); dicrofenac (0.8, 4 and 20). Endogenous prostacyclin (PGI₂) and PGE₂ in fundic mucosa were determined by radioimmunoassay. The three compounds produced fundic mucosal lesions in a dose-dependent manner. However, tiaprofenic acid and dicrofenac were both less potent than indomethacin in producing gastric mucosal lesions at similar antiinflammatory doses. Mucosal PGE₂ content was abolished by the three compounds in the following doses (mg/kg): indomethacin (4 and 20); tiaprofenic acid (6 and 30); dicrofenac (20). Mucosal PGI₂ was maintained around 50% of the control value in rats given tiaprofenic acid in a dose of 6 mg/kg or dicrofenac in a dose of 4 mg/kg, while indomethacin in a dose of 4 mg/kg markedly reduced mucosal PGI₂ to 17% of the control value. In larger doses, tiaprofenic acid and dicrofenac were also significantly less potent in reducing mucosal PGI₂ than idomethacin. These results suggest that the difference in ulcerogenicity between idomethacin and the other two compounds was closely related to their potency in decreasing PGI₂ in the gastric (fundic) mucosa.     

Protective Effects of Quercetin and Melatonin on Indomethacin Induced Gastric Ulcers in Rats

Background: Medications to prevent the development of NSAID-induced gastric ulcers have a large range of unpleasant side effects. Recent efforts have been focused on determining safer alternative nontoxic and natural forms of anti-ulcer treatments. Methods:Twenty-four male rats were divided into 4 groups: 1: control group that received no treatment; 2: the ndomethacin-treated group that received 20 mg/kg of indomethacin for 2 days to induce the development of gastric ulcers; 3: quercetin-treated group that in addition to the indomethacin treatment, received 50 mg/kg of quercetin 6 hours after and then daily for 14 days and; 4: the melatonin-treated group which received 20 mg/kg of melatonin 6 hours after each indomethacin treatment and then daily for 14 days. All drugs were administered orally. The following parameters were assessed in each group: mean ulcer index of gastric tissue, gastric acid volume and pH, oxidative stress markers: malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH), inflammatory markers: PGE-2, TNF-α, and IL-10, nitric oxide (NO) levels and the relative gene expression of BAX, BCL-2 and COX-2 by real time PCR.Results:Our findings revealed that the indomethacin-treated group had a significantly increased (p< 0.05) ulcer index, gastric acid volume, and elevated levels of stress, inflammatory, and apoptotic markers compared to controls. In the groups that received quercetin or melatonin, these factors were all significantly decreased (p< 0.05). Between quercetin and melatonin, there was no significant difference in their gastroprotective effect. Conclusion:Both quercetin and melatonin had protective antioxidant, anti-inflammatory and antiapoptotic activity against indomethacin-induced gastric ulcers.Key Words: Gastric ulcer, Indomethacin, Melatonin, Quercetin     

The effect of graded single oral doses of prostacyclin on the nucleic acid content of rat gastric mucosa.

Graded single oral doses of prostacyclin significantly enhance in dose-dependent manner the DNA and RNA content of rat gastric fundic mucosa, - resulting in a decreased RNA/DNA ratio. This latter phenomenon is convincing sign of new cell formation. In the antral region no significant changes could be encountered but the RNA content showed a tendency-like elevation, evoking an elevated RNA/DNA ratio, which corresponds to de novo protein synthesis. The diversity of the noted changes gives further evidence to the tenet the antral and the fundic gastric mucosa of the rat reacts differently toward external stimuli.     

Further analysis of prostacyclin's effect on rat gastric mucosal nucleic acid content.

Graded single and multiple oral doses of prostacyclin enhance, in a direct dose-dependent manner, the DNA and RNA content of rat gastric (antral and fundic) mucosa, resulting in a decreased RNA/DNA ratio. This latter phenomenon is a convincing sign of new cell formation. The arithmetical (theory of functions) analysis of the data resulted in equations, defined mathematically, of prostacyclin's dose-dependent effect.     

Gastric anti-ulcerogenic drug effect. A possible mechanism of its molecular basis.

During experimental gastric ulceration in rats an elevation in the mucosal cAMP/cGMP ratio can be encountered. The cause of this significant elevation is mainly (but not entirely) the dramatic fall of the cGMP level. Similar observations were obtained with prostacyclin application (100 micrograms/kg, p.o.), too. This prostaglandin derivative is well known, among others, because of its pronounced anti-ulcerogenic (cytoprotective) effect, too. Other substances of different molecular structure and properties may also exert such effect. The exact mechanism of action of this above-mentioned cytoprotection is still not completely understood. H2-receptor blocker drug cimetidine, given in such small dose (5 mg/kg, p.o.) which does not interfere with gastric acid secretion, also exerts very significant cytoprotective effect in stress (restraint)- and drug (indomethacin)-induced gastric ulcer models. Under cimetidine effect--together with a noticeable endogenous prostacyclin mobilization--the gastric mucosal cAMP/cGMP ratio was also strongly elevated. We conclude that this elevation in the mucosal cAMP/cGMP ratio might be a possible molecular basis of the gastric cytoprotective (anti-ulcerogenic) drugs but it needs further investigations whether all substances exerting cytoprotective effect, e.g. atropine, somatostatin, sulfhydryl drugs, etc., have the same "shifting" property or not? Moreover the phenomenon of the so-called "adaptive cytoprotection" can not be ruled out completely either, therefore this problem needs attention, too.     

Possible prostaglandin-dopamine interactions during experimental gastric ulcer formation

The effects of dopamine (DA) agonists and antagonists were investigated on indomethacin--and restraint stress (6 hr at RT)--induced gastric ulcer formation in rats. The DA-agonists, apomorphine and bromocryptine (both at 5 mg/kg) significantly attenuated the frequency and severity of gastric mucosal lesions in both experimental models. The DA-antagonist, haloperidol (0.05 and 1.0 mg/kg) aggravated the gastric ulcerogenesis of both indomethacin and stress, the effects with the lower dose being statistically significant. Haloperidol (0.05 mg/kg) also prevented the cytoprotective effects of apomorphine on indomethacin-ulcers. The atypical DA-antagonist, sulpiride (10 and 50 mg/kg), however, showed differential dose- and model-specific effects. Whereas, the lower dose attenuated indomethacin-ulcers, the higher dose (50 mg/kg) tended to aggravate this phenomenon. The trend of results were reversed in the restraint stress model. Indomethacin (1 mg/kg) aggravated stress-ulcers, an effect which was also appreciably neutralised by apomorphine (5 mg/kg) pretreatment. These results are discussed in light of possible prostaglandin-DA interactions during such experimental gastric pathology.     

前列环素参与低氧,高二氧化碳脑血管张力调节

本工作是在初生小牛基底动脉血管条上,用前列环素合成酶抑制剂—消炎痛（Ｉｎｄｏｍｅｔｈａｃｉｎ）研究前列环素及内皮细胞在低氧高二氧化碳脑血管扩张机制中的作用。实验结果表明,消炎痛对常氧下脑血管张力没有影响,但可抑制低氧高二氧化碳引起的脑血管扩张反应。去除内皮细胞后低氧、高二氧化碳扩张脑血管的作用显著减小,此时再给予消炎痛对血管张力无明显作用。由此提示,前列环素和内皮细胞参与低氧,高二氧化碳的脑血管扩张作用,而前列环素是来源于内皮细胞。     

Gastroprotective effect of leptin in indomethacin-induced gastric injury

This study investigated the involvement of neutrophil infiltration, disturbances in nitric oxide (NO) generation and oxidative stress in indomethacin-induced gastric ulcer, and the possible gastroprotective potentials of leptin, known for its angiogenic effect. Male Wistar albino rats (180–220 g) were allocated into a normal control group, ulcer control group (received a single dose of indomethacin 40 mg/kg p.o.) and an ulcer group pretreated with leptin (10 μg/kg i.p. 30 min before ulcer induction). The animals were killed 6 h after indomethacin administration and their gastric juice, serum and mucosal tissue were used for gastric injury evaluation. Indomethacin produced multiple lesions in glandular mucosa, evidenced by marked increase in gastric ulcer index (GUI) accompanied by significant increases in gastric juice acidity, tissue myeloperoxidase (MPO) activity, serum NO and tissue conjugated diene (CD), and marked decreases in tissue NO and glutathione (GSH) as well as glutathione reductase (GR) and superoxide dismutase (SOD) activities, while gastric juice mucin and tissue glutathione peroxidase (GPx) were not affected. Leptin exerted significant gastroprotection as evidenced by significantly decreased GUI and attenuated neutrophil infiltration. Leptin significantly increased mucin and tissue NO, restored GR and SOD activities and up-regulated GPx activity. It failed to affect acidity, serum NO, GSH and CD. These results suggest that leptin confers significant gastroprotection against indomethacin-induced injury through interfering with neutrophil infiltration, NO production and oxidative stress.     

The effect of different prostaglandins on gastric mucosal intracellular second messenger system in the rat.

After an oral administration of 100 micrograms/kg dose, the investigated prostaglandins: PGF2 alpha, PGE2 and a synthetic PGE2 derivative: FCE-20700, exerted a significant effect on cAMP and cGMP content of both parts (antral and fundic) of gastric mucosa, resulting in an elevated cAMP/cGMP ratio, while 6-keto-PGF1 alpha, the stable break-down product of prostacyclin, was inactive. Since the above-mentioned phenomenon seems to be proportionate to the cytoprotective (anti-ulcerogenic) property of the investigated prostaglandins, this cAMP/cGMP ratio "shift" is interpreted as a probable (molecular) sign of the reparative, (anti-ulcerogenic) processes.     

The anti-gastric ulcer effect of Gynostemma pentaphyllum Makino.

Gynostemma pentaphyllum is an oriental medicinal herb reputed to have broad-spectrum activities. The plant's principal saponin components are structurally similar to those found in ginseng plants and this similarity is assumed to be responsible for the claimed activities. The present study was undertaken to evaluate a G. pentaphyllum butanol fraction (GPB) for its anti-gastric ulcer activity using experimental models. Oral administration of the GPB at 200 and 400 mg/kg body wt. significantly inhibited gastric ulcer formation induced by indomethacin, HCl/EtOH and water-immersion restraint stress in rats. In pylorus-ligated rats, pretreatment with the GPB had no effect on gastric volume, pH or acidity output, thus indicating a lack of anti-secretory effect. In ethanol-induced ulcerated rats, gastric wall mucus and hexosamine content were markedly preserved by GPB pretreatment. The findings indicate that the butanol fraction of G. pentaphyllum possesses gastroprotective potential related to the preservation of gastric mucus synthesis and secretion.     

Implication of gastrin in cyclooxygenase-2 expression in Helicobacter pylori infected gastric ulceration

Gastroduodenal ulcerations have worldwide distribution and the infection with Helicobacter pylori (HP) has been implicated in pathogenesis of this disease. The HP infection is usually accompanied by hypergastrinemia and enhanced generation of prostaglandins (PG), both implicated in the pathogenesis of peptic ulcerations but no study has been undertaken to assess the relationship between the HP infection and coexpression of gastrin and cyclooxygenases (COX), the rate limiting enzymes in the PG production. Since HP infection, usually accompanying peptic ulcerations, results in increased release of gastrin, a potent gastric mitogen that might be capable to induce COX-2 and to generate PG, we decided 1) to compare the seroprevalence of HP and its cytotoxic protein, CagA, in gastric ulcer patients with those in age- and gender-matched controls; 2) to determine the gene expression of gastrin and its receptors (CCK(B)-R) at the margin of gastric ulcer and in the mucosa of antrum and corpus before and after successful eradication of HP, 3) to assess the plasma levels and gastric luminal contents of gastrin before and after HP eradication and 4) to examine the mRNA and enzyme protein expression of COX-1 and COX-2 as well as the PGE2 generation in ulcer margin tissue and gastric antral and fundic mucosa before and after the HP eradication. The trial material included 20 patients with gastric ulcer and 40 age- and gender-matched controls. Anti-HP and anti-CagA IgG seroprevalence was estimated by specific antisera using ELISA tests. Gene expressions of gastrin, CCK(B)-R, COX-1 and COX-2 were examined using RT-PCR with beta-actin as a reference and employing Western blotting for COX-2 expression, while gastrin and PGE2 were measured by RIA. All gastric ulcers were located at smaller curvature within the antral mucosal area. The seroprevalence of HP, especially that expressing CagA, was significantly higher in gastric ulcers (85%) than in controls (62.5%). Both gastrin and CCK(B)-R mRNA were detected by RT-PCR in ulcer margin and gastrin mRNA was overexpressed in remaining antral mucosa, while CCK(B)-R mRNA was overexpressed in fundic mucosa of HP infected patients. Similarly, COX-2 mRNA and protein were found in margin of gastric ulcer and in the HP infected antral and fundic mucosa but not in the mucosa of HP eradicated patients in whom ulcers completely healed and gastrin was expressed only in antrum, CCK(B)-R only in corpus, while COX-1 was detected both in antrum and corpus. HP positive gastric ulcer patients showed about three times higher levels of plasma immunoreactive gastrin and about 50% higher luminal gastrin contents than the HP negative controls and this increased plasma and luminal gastrin was normalized following the HP eradication. A significant fall in gastrin and CCK(B)-R mRNA expression was noticed six weeks after HP eradication in gastric antral and fundic mucosa, while COX-2 mRNA completely disappeared after this treatment. We conclude that 1) HP infected gastric ulcer margin coexpresses gastrin, its receptors (CCK(B)-R), and COX-2; 2) HP infection may be implicated in gastric ulceration via increased release of gastrin that could be responsible for the overexpression of COX-2 that in turn could help ulcer healing through the stimulation of mucosal cell growth, restoration of the glandular structure and angiogenesis in the ulcer area and 3) gastrin produced in HP infected antral mucosa seems to be involved in the induction of COX-2 and PG production by this enzyme and this may contribute to the ulcer healing.     

Prostacyclin-mediated compensatory mechanism in the coronary circulation during acute NO synthase blockade

Nitric oxide (NO) in contrast to most prostanoids, plays a major role in the maintenance of coronary arterial tone under physiological conditions. However, in case of endothelial damage or other NO-depleting situations the importance of other vasodilating mechanisms may be increased. The aim of the present study was to investigate the crosstalk between the L-arginine - NO and the prostanoid systems in isolated rat hearts. Coronary flow and cardiac dynamics were measured in a standard Langendorff perfusion system. Application of indomethacin in the perfusion media failed to change coronary flow. Administration of L-NA, however, significantly decreased coronary flow by 24.8 +/- 2.3% (p < 0.01 vs. untreated control). In the presence of indomethacin, L-NA decreased coronary flow to an even greater extent by 35.8 +/- 5.2% (p < 0.05 vs. L-NA alone). Treatment of the preparations with L-NA or indomethacin failed to change cardiac work, coapplication of both drugs together, however, decreased cardiac work by 45 +/- 11% (p < 0.05 vs. untreated control). Heart rate remained constant throughout the experimental period and did not differ significantly between the treatment groups. The prostacyclin content of the effluent from the L-NA treated hearts was significantly higher than that of controls. We conclude that in case of decreased NO levels in the coronary circulation, arterial tone is maintained by prostacyclin production.     

Prostacyclin-induced activation of 3'-5'-cyclic adenosine monophosphate-dependent protein kinase in rat antral and fundic gastric mucosa.

The present investigations showed that after oral prostacyclin administration (100 micrograms/kg) as soon as the intracellular level of cAMP is elevated the activation of cAMP-dependent protein kinase follows in both parts (antrum and fundus) of rat gastric mucosa. The enzyme activation seems to be more significant in the fundic region which is in a complete agreement with the previously published results, i.e. the fundic mucosa reacts with de novo protein synthesis toward noxious agents (resulting finally in new cell formation), while the antral mucosa is more durable against damaging noxae. Taking into consideration all available data in the literature it seems that the intracellular effect of the exogenously administered prostacyclin in the gastric mucosa is a polyphasic effect, which contains the following consecutive steps: 1. Binding to the cell surface; 2. Effect on the intracellular second messenger system, (cAMP, cGMP); 3. Activation of the calmodulin system; 4. cAMP-dependent protein kinase activation; 5. DNA, RNA changes; 6. Influence on protein synthesis, and finally; 7. New cell formation.     

胃复春片联合西药治疗胃溃疡的临床疗效

目的：探讨胃复春片联合西药治疗胃溃疡的临床疗效。方法：选取本院收治的胃溃疡患者80 例,随机分为观察组和对照组, 每组40 例。对照组给予奥美拉唑和阿莫西林治疗,观察组在对照组基础上加用胃复春治疗。观察并比较两组治疗前后血清TNF- 琢及IL-8 水平变化、临床疗效、幽门螺杆菌根除率、不良反应发生率,并采用采用视觉模拟评分法（Visual Analogue Scale/Score,V AS）评定治疗前后的腹部疼痛程度。结果：观察组治疗总有效率为92.50 %,对照组治疗总有效率为80.00 %,两组差异有统计学意 义（P＜0.05）;两组治疗后的VAS评分较治疗前均有明显下降（P＜0.05）,但观察组优于对照组（P＜0.05）;观察组幽门螺旋杆菌清 除率为97.50 %,显著高于对照组的77.50 %（P＜0.05）;观察组不良反应发生率为12.50 %,明显低于对照组的30.00 %（P＜0.05）。 两组治疗后的TNF-alpha、IL-8 浓度均有所下降,且观察组下降程度明显高于对照组,差异具有统计学意义（P＜0.05）。结论：对于胃溃 疡患者,在西药治疗的基础上加以胃复春片治疗,可以显著提高治疗效果,缓解临床症状,且不良反应少。     

Bidirectional Crosstalk between Stress-Induced Gastric Ulcer and Depression under Chronic Stress

Stress contributes to a variety of diseases and disorders such as depression and peptic ulcer. The present study aimed to investigate the correlation between stress ulcer and depression in pathogenesis and treatment by using chronic stress depression (CSD), chronic psychological stress ulcer (CPSU) and water immersion restrain stress models in rats. Our data showed that the ulcer index of the animals after CSD exposure was significantly higher than that of controls. Depression-like behaviors were observed in rat after CPSU exposure. Fluoxetine hydrochloride significantly reduced the ulcer index of rats exposed to CPSU stress, while ranitidine inhibited depression-like behavior of the animals in CSD group. The ulcer index of rats administered with mifepristone after CPSU stress was markedly reduced compared to CPSU group, although there was no significant difference in the depression-like behavior between mifepristone-treated CSD group and naive controls. We also found that the rats exposed to CPSU or CSD stress displayed a lower level of corticosterone than naive controls, however, the acute stress (AS) group showed an opposite result. Additionally, in order to study the relevance of H₂ receptors and depression, we treated the CSD group with cimetidine and famotidine respectively. The data showed that cimetidine inhibited depression-like behavior in CSD rats, and famotidine had no impact on depression. Overall our data suggested that the hypothalamic-pituitary-adrenal (HPA) axis dysfunction may be the key role in triggering depression and stress ulcer. Acid-suppressing drugs and antidepressants could be used for treatment of depression and stress ulcer respectively. The occurrence of depression might be inhibited by blocking the central H₂ receptors.     

Cross talk of shear-induced production of prostacyclin and nitric oxide in endothelial cells

We tested the hypothesis that vessel homeostasis is maintained through the cross talk of shear-induced production of prostacyclin and nitric oxide (NO). Confluent human umbilical vein endothelial cells (HUVEC) were exposed to fluid shear stress at 15 dyn/cm(2) using a cone-plate device, and the concentrations of 6-keto-PGF(1alpha) and NO metabolites (nitrate and nitrite) in the medium were measured with radioimmunoassay and the Greiss method, respectively. Compared with static control, shear stress increased cumulative prostacyclin production by twofold after 90 min of exposure. Inhibition of NO synthase enhanced flow-induced prostacyclin production by twofold without affecting the baseline production. Guanylyl cyclase inhibitor enhanced flow-induced prostacyclin production to the same degree. In contrast, a stable agonist of cGMP attenuated the rapid early phase of flow-dependent prostacyclin production. Shear-induced NO metabolite production was unaffected even after indomethacin inhibited prostacyclin production. We conclude that NO shows an inhibitory effect on prostacyclin production under shear stress and that vessel homeostasis may be maintained through an increase in prostacyclin production when NO synthesis is impaired in endothelial cells.