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.     

Effect of nicotine on gastric mucosal blood flow and acid secretion.

The effects of an intravenous infusion of nicotine at a dose of 2 . 5, 5 . 0, 7 . 5, or 10 . 0 micrograms kg-1h-1 on pentagastrin-stimulated gastric mucosal blood flow and acid secretion were investigated in eight healthy male non-smokers. Each dose was tested in two males. Gastric neutral red clearance served as a measure of mucosal blood flow. Nicotine reduced volume secretion, acid secretion, and neutral red clearance in a dose dependent manner. In five healthy male smokers smoking of five cigarettes per two hours induced similar changes to the intravenous infusion of 5 micrograms kg-1h-1 nicotine. As volume secretion was inhibited more than neutral red clearance, it is concluded that nicotine increases blood supply to the gastric mucosa relatively to the reduced gastric secretion. Nicotine is either not associated with the development of peptic ulcers, or it exerts its ulcerogenic action via other mechanisms than change of acid secretion and gastric mucosal blood flow.     

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.     

褪黑激素对胃黏膜的保护作用及其机制

目的：探讨褪黑激素和血清素对鼠胃酒精性溃疡及黏膜血流的影响。方法：制备胃在体动物模型。分别皮下注入血清素及同容积生理盐水。用褪黑激素及同容积蒸馏水作为浸育液分别放入各组鼠的胃腔中。30min未毕毕胃黏膜血流后,采用40％的酒精作为浸育液分别放入各组鼠胃腔中,继续检测胃黏膜血流并测量胃黏膜损伤指数。结果：褪黑激素和血清素两者均不能损伤鼠胃黏膜,但血清素可降低胃黏膜血流,且与其剂理相关。褪黑激素可减轻由酒精引起的胃黏膜损伤和胃黏膜血流减少,而血清素可加重酒精引起的胃黏膜损伤和胃黏膜血流减少,但可被褪黑激素部分逆转。结论：胃黏膜的损伤与胃黏膜血流有关,但不是溃疡形成的唯一因素。因此,能拮抗血清的褪黑激素可作为在胃肠道作用的调节剂。     

Role of dorsal motor nucleus of vagus in gastric function and mucosal damage induced by ethanol in rats

Experimental evidence indicates that the autonomic nervous system, especially the cholinergic pathway, modulates the mucosal defensive mechanism and affects mucosal damage in the stomach. The present study investigated the role of the dorsal motor nucleus of vagus (DMV) in gastric function and its influences on ethanol-induced mucosal damage in pentobarbitone-anesthetized rats. Electrolytic lesion of the DMV as compared with sham operation and lesions of other brain areas, eg, nucleus reticular gigantocellularis and cuneate nucleus, reduced the basal gastric mucosal blood flow (GMBF) and also the blood flow after ethanol administration. The same operation did not affect the acid secretion either in the basal state or during the ethanol treatment period. Lesions at the caudal half of the DMV produced a bigger depression of GMBF when compared with lesion at the rostral half. In the sham-operated rats, ethanol induced severe hemorrhagic lesions in the gastric glandular mucosa, and this was significantly potentiated by lesions at the DMV, especially in the caudal half. The present findings indicate that acute DMV damage at the caudal half markedly affects the GMBF but not the acid secretion. The action on GMBF may contribute to the aggravation of ethanol-induced gastric damage in rats. These data reinforce the idea that the central vagal pathway, especially the caudal half of the DMV, plays a significant role in the modulation of GMBF, which in turn affects the integrity of gastric mucosal barrier.     

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.     

The contrasting influence of chronic nicotine intake on gastrin and gastric acid secretion

The effects of chronic nicotine treatment on gastric acid secretion stimulated by subcutaneous injection of pentagastrin, as well as on serum gastrin levels and the stomach parietal cell population, were examined. Rats drank a solution of nicotine 25 μg/mL tap water for periods of 10, 30 or 45 days. Pentagastrin increased the gastric secretory volume and acid output in pylorus-ligated control animals that drank tap water. Animals given nicotine in their drinking water for 10, 30 or 45 days showed increased basal gastric secretion and acid output. Pentagastrin produced maximum stimulatory effects at lower dose levels of 50 μg/kg in the 10-day treatment group and 25 μg/kg in the 30- or 45-day treatment groups; however, the maximum responses to pentagastrin in all nicotine-treated batches were comparable to those of their corresponding controls. Serum gastrin levels remained unchanged from the 10th day of nicotine treatment, whereas the levels in the control animals continued to rise with age. Nicotine 25 μg/mL drinking water given for 10, 30 or 45 days caused no significant changes in the parietal cell population, mucosal surface area or mucosal thickness. These findings are consistent with the idea that chronic nicotine administration, for at least 10 days, will lead to increased muscarinic receptor sensitivity; basal acid secretion is consequently elevated, and this in turn may depress gastrin secretion.     

Effect of Nicotine and Alcohol Pretreatment on the Gastric Mucosal Damage Induced by Aspirin, Phenylbutazone, and Reserpine in Rats

The effect of nicotine and alcohol pretreatment by feeding nicotine (2.5 mg/100 ml), alcohol (25%, v/v) and their combination (nicotine 2.5 mg/100 ml + alcohol 25%, v/v) in drinking water ad libitum for 21 days was studied on the gastric mucosal damage induced by aspirin, phenylbutazone, and reserpine in rats. When given alone, neither nicotine nor alcohol produced any visibly discernible gastric lesions. Their concurrent administration, however, produced minor injury to the gastric mucosa appearing as 5-7 circular ulcers of less than 1 mm in diameter. Pretreatment with nicotine, alcohol, and their combination resulted in the significant augmentation of gastric ulcers produced by aspirin, phenylbutazone, and reserpine. The augmentation of gastric lesions in the group pretreated with the combination of nicotine and alcohol was significantly greater than in the groups treated by either of them alone. The effect of nicotine on the mucus neck cell population of the gastric mucosa and pancreatic bicarbonate secretion, and the gastric mucosal damaging effect of chronic alcohol treatment may be responsible for the potentiation of ulcerogenic effects of aspirin, phenylbutazone, and reserpine.     

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.     

Modulating Action of Melatonin on Serotonin-Induced Aggravation of Ethanol Ulceration and Changes of Mucosal Blood Flow in Rat Stomachs

Effects of melatonin and serotonin on ethanol ulceration and mucosal blood flow in the rat stomach were investigated. Melatonin and serotonin (5-HT) administration did not produce observable gastric injury in the ex vivo stomach, but the 5-HT dose dependently reduced glandular mucosal blood flow (GMBF) in this organ. Ethanol depressed GMBF and induced visible glandular mucosal injury. The latter effect was prevented by melatonin preincubation. Serotonin pretreatment aggravated the gastric mucosal injury and GMBF changes induced by ethanol; these actions were partially reversed by melatonin. The findings indicate that the GMBF and gastric injury are related; the reduction in FMBF, however, may not be the sole factor responsible for ulceration. The antagonistic effects of melatonin on 5-HT action on the stomach suggest that melatonin may act as a modulator for 5-HT action on the gastrointestinal tract.     

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.     

Topical nicotine protects rat gastric mucosa against ASA-induced damage a role for mucosal fluid secretion in cytoprotection

Acute intragastric nicotine administration has previously been shown to protect against ethanol-induced gastric mucosal damage. The aim of this study was to examine the effects of acute nicotine exposure on ASA-induced gastric mucosal damage and to determine if nicotine's protective effect is secondary to an increase in mucosal blood flow or in mucosal fluid secretion, as reflected by changes in the juxtamucosal pH gradient and volume of intragastric fluid. Mucosal blood flow, using a laser Doppler flowmeter, juxtamucosal pH gradient (depth, magnitude, and surface pH), using antimony microelectrodes, and changes in volume of luminal bathing solutions were measured in ratex vivo gastric chamber preparations prior to and after a 10-min exposure to topical nicotine (1 mg in 8 ml of 0.2 M mannitol in 50 mM HCl), or to mannitol-HCl solution (vehicle). This was followed by application of acidified ASA (80 mM in 160 mM HCl) to the chambered mucosae for 10 min. Lesion area, expressed as the percentage of total glandular mucosa which was damaged, was significantly (P<0.05) reduced by nicotine pretreatment. Blood flow decreased with nicotine exposure by 18.4%, compared to 13.6% in the control group (NS). Both gradient depth and gastric fluid volume increased significantly in the nicotine group (P<0.05) compared to controls. Yohimbine pretreatment prevented both the increase in juxtamucosal pH gradient depth and the protective effect of nicotine. These results suggest that acute intragastric nicotine exposure protects against ASA-induced gastric damage in rats. This protection is not due to increased mucosal blood flow, but may be due to increased mucosal secretion, as reflected by an increase in the pH gradient depth, and an increase in the intragastric volume.This research was supported by a grant from the Natural Sciences and Engineering Research Council of Canada     

Effects of acid secretagogues on rat gastric mucus glycoprotein content and gastric mucosal resistance

In our previous reports, low dose acid secretagogues caused increase in corpus mucus glycoprotein content in rats. This increase was not due to the direct action of protons. The present study was conducted to determine whether this increase has a mucosal function or not Rats were given histamine (0.8 mg/kg) intraperitoneally or tetragastrin (12 micrograms/kg) subcutaneously. One hour following the acid secretagogues administration, the animals were given 1 ml of 30, 40 or 50% ethanol orally and then sacrificed after one hour. Gastric mucus glycoproteins were isolated from the corpus region of stomach. The following results were obtained: 1) Histamine prevented the gastric mucosal damage and the decrease of corpus mucus glycoprotein content induced by 40% ethanol ingestion. 2) Tetragastrin prevented the gastric mucosal damage induced by 30 approximately 50% ethanol ingestion and the decrease of corpus mucus glycoprotein content induced by 40 approximately 50% ethanol ingestion. Based on these results, the increase of corpus mucus glycoprotein content induced by acid secretagogues has a mucosal function. Moreover, tetragastrin strengthened the mucosal defence together with acid secretion.     

Effects of nitric oxide on gastric ulceration induced by nicotine and cold-restraint stress

AIM: Stress induces gastric ulceration in human and experimental animals. People tend to smoke more cigarettes when under stress. Nitric oxide (NO) and nicotine have opposing effects on gastric integrity. The present study examined the possible therapeutic benefit of NO in nicotine-treated rats with stress-induced gastric ulceration. METHODS: Rats drank a nicotine solution while control rats drank tap water for 20 days. The alkoloid was then replaced by water with or without supplementation of isosorbide dinitrate (NO donor) for an additional 10 days. Isosorbide dinitrate was given twice shortly before experiments (acute) or three times daily by oral gavages for 10 days after the rats stopped drinking nicotine solution. At the end of experiments, ulcer index, gastric adhesion mucus content and MPO activity were measured and analysed. RESULTS: Nicotine treatment decreased gastric mucus content and intensified stress-induced gastric ulcer. A higher ulcer index persisted even after the rats stopped drinking nicotine solution for 10 days. Acute NO donor showed no benefit on both mucus and ulcer index in nicotine treatment or/and stress condition. Chronic NO donor treatment reversed the worsening action of nicotine in stomach. Stress increased gastric mucosal myeloperoxidase (MPO) activity, which was antagonized by chronic NO treatment. However, nicotine was unlikely to change mucosal MPO activity. CONCLUSION: The intensifying action of nicotine on stress-induced gastric ulceration persists for 10 days after cessation. Nicotine treatment significantly decreases gastric mucus content that can be restored by chronic NO donor treatment. The present study suggests that NO antagonizes the ulcerogenic action of nicotine through a cytoprotective way.     

Pathways mediating pentagastrin-induced mucosal blood flow response in rat stomachs

The mechanisms of pentagastrin-induced gastric mucosal blood flow (GMBF) response were investigated in anesthetized rats. A rat stomach was mounted on anex vivo chamber, perfused with saline, and GMBF was measured by a laser Doppler flowmetry simultaneously with acid secretion. Pentagastrin infused intravenously produced a dose-dependent increase of GMBF as well as acid secretion, and its effect reached a maximum at 120 µg/kg/hr (maximal dose). Pretreatment with omeprazole (60 mg/kg, intraperitoneally) completely inhibited the acid secretory response and the enhancement of GMBF induced by both submaximal (60 µg/kg/hr) and maximal doses of pentagastrin. In contrast, the luminal perfusion with glycine (200 mM) to remove luminal H⁺ almost totally attenuated the increase of GMBF caused by the submaximal dose of pentagastrin, without any effect on acid secretion, but partially suppressed such GMBF responses caused by the maximal dose. Subcutaneous pretreatment with indomethacin, a cyclooxygenase inhibitor, significantly mitigated GMBF response caused by both submaximal and maximal doses of pentagastrin, whereas 8-phenyltheophylline (8-PT), an adenosine antagonist, showed a significant inhibition of GMBF response caused by only the maximal dose. However, the combined administration of 8-PT with glycine perfusion further attenuated GMBF response caused by the maximal dose of pentagastrin, and the additional treatment with indomethacin completely blocked this GMBF response. We conclude that pentagastrin-induced GMBF responses are mediated by at least two different pathways; one is related to luminal H⁺ and the other to the parietal cell activity, depending on the dose of pentagastrin. In addition, the latter pathway may be mediated by adenosine, while endogenous prostaglandins may be involved in both pathways.     

Chronic nicotine intake causes vascular dysregulation in the rat gastric mucosa.

Chronic cigarette smoking has adverse effects on peptic ulcer disease because the healing of ulcers is delayed and the incidence of relapses is enhanced. Short term intake of nicotine induces vascular damage in the rat gastric mucosa, but the pathophysiological mechanisms of nicotine's action in the stomach are largely unknown. In this study rats were treated with nicotine, added to their drinking water, for 50 days. They were then anaesthetised and their stomachs perfused with acidified acetylsalicylic acid (ASA). Chronic nicotine treatment failed to change the effects of acidified ASA to induce gastric mucosal acid back diffusion, haemorrhagic damage and bleeding. Basal blood flow in the gastric mucosa was also unchanged by chronic nicotine intake, whereas the mucosal hyperaemia evoked by ASA induced acid back diffusion was averted. The concentrations of sulfidoleukotrienes were significantly augmented in the gastric wall of nicotine treated rats. These data show that chronic nicotine intake causes dysregulation of the gastric microcirculation, an effect that is associated with biochemical changes in the stomach. This study thus substantiates the adverse effects of smoking on gastric mucosal pathophysiology. These data suggest that inappropriate regulation of gastric mucosal blood flow inhibits recovery from gastric mucosal injury in smokers.     

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.     

Intragastric pH in the gastroprotective and ulcer-healing activity of aluminum-containing antacids.

Antacids containing aluminum have been shown to stimulate the protective processes in the gastric mucosa and to enhance the healing of chronic gastroduodenal ulcerations, but the mechanisms of these effects are still unexplained. This study was designed to compare the protective effects of unmodified and acidified (pH 2.0) Maalox 70 and Al(OH)3 on the formation of acute gastric mucosal lesions induced by absolute ethanol, taurocholate, acidified aspirin and stress, and to determine the role of gastric acid in healing of chronic gastroduodenal ulcerations by these antacids in rats. Acidified Maalox 70 and Al(OH)3 were significantly more potent than unmodified agents against all four tested types of acute mucosal lesions, and this action was probably due to their 'mild irritant' effect as evidenced by extensive exfoliation of the surface epithelial cells observed microscopically after the exposure of the mucosa to these agents. Mucosal generation of prostaglandins does not appear to be involved in the gastroprotection by acidified Maalox because the pretreatment with indomethacin did not affect this protection. In contrast to the protective effect, the ulcer-healing capacity of Maalox or Al(OH)3 does not appear to be dependent upon the presence of gastric acid because the reduction or elimination of endogenous acid by the pretreatment with ranitidine or omeprazole did not affect the healing of gastroduodenal ulcerations. We conclude that aluminum-containing antacids induce the mucosal protection that is enhanced in the presence of luminal acid but exhibit an ulcer-healing property that appears to be unrelated to gastric acid secretion or mucosal generation of prostaglandins.     

Morphological and functional gastric cytoprotection by prostaglandin in rats receiving absolute ethanol orally.

Pretreatment with prostaglandins at non-antisecretory doses protects the gastric mucosa, including the parietal cells, from deep necrosis produced by intragastric administration of necrotising agents such as absolute ethanol. Whether the parietal cells also retained their ability to secrete acid when rats were pretreated with a prostaglandin, in spite of exposure to ethanol, was investigated. Gastric acid secretion was abolished 4 hours after ethanol, and secretion returned to control values only after 5-6 days. Pretreatment with a single, non-antisecretory dose of 16, 16-dimethyl prostaglandin E2 (dm PGE2) maintained acid secretion, in spite of exposure to absolute ethanol. Absolute ethanol caused histological changes - extensive gastric mucosal necrosis (through the muscularis mucosae), oedema, haemorrhages, polymorphonuclear infiltration, and formation of granulation tissue - that were maximal 24-48 hours after ethanol and persisted for 2 to 4 weeks. None of these changes were present in animals treated with the prostaglandin. It is concluded that a single oral pretreatment with dmPGE2 protects the gastric mucosa against not only the morphological damage of absolute ethanol (preventing necrosis, haemorrhages, and polymorphonuclear infiltration) but also the functional damage (maintaining the acid secretory function of parietal cells).     

Somatostatin increases the ratio between gastric mucosal blood flow and gastric acid and pepsin secretion in dogs

The effects of somatostatin on gastric mucosal blood flow (GMBF), acid secretion, and pepsin secretion were evaluated. Conscious gastric fistula dogs were used, with neutral red clearance as the method for estimating the mucosal blood flow. Somatostatin inhibited the pentagastrin- and bethanechol-stimulated gastric acid and pepsin secretion and resulted in an absolute decrease in mucosal blood flow. The ratios between GMBF and secretion (acid and pepsin) were increased during somatostatin infusion, which suggests a relative increase in mucosal blood flow and independent inhibition of gastric secretion. It may be concluded from this study that the acid- and pepsin-inhibitory effects of somatostatin are not mediated by changes in the GMBF.