Rat Gastric Acid Research Articles

The Effect of Avocado Leaf Ethanol Extract (Persea Americana Mill) on Aspirin-Induced Reduction of Gastric Acid in Rats

Gastritis is inflammation of the mucosal lining of the stomach. Gastritis can be caused by several things, one of which is the use of anti-inflammatory drugs which can damage the gastric mucosal lining which occurs in two ways, namely local and systemic. Local damage is caused by being lipophilic and acidic, while systemic damage is caused by a significant decrease in prostaglandin production. Avocado leaf ethanol extract contains flavonoids and saponins which have anti-inflammatory effects and inhibit histamine secretion. This study aims to analyze the activity of ethanol extract of avocado leaves in reducing gastritis in vivo in rats induced by apirin. Samples of 60 mice weighing 150-200 g were divided into 5 groups, namely negative control group (CMC Na), positive control (Simetidine), ethanol extract of avocado leaves 100, 200, 400 mg/Kg BW. Mice were fasted for 24 hours, induced by aspirin 400 mg/KgBW for 24 hours and mice remained fasted. then given treatment according to group division for 8 days. Every 2 days after treatment, 3 mice were taken from each group to be sacrificed by dislocation, the mice's stomachs were dissected, all gastric fluid was collected and the stomach contents were removed and then washed with 0.9% NaCl solution. Gastric fluid is used to check fluid concentration and pH. Then the rat's stomach was opened by stretching it to count the number of ulcers and the ulcer index that occurred. The results of the study showed that the 400 mg/KgBW avocado leaf ethanol extract group had an anti-inflammatory effect that was almost the same as Cimetidine, this was shown by the results of decreasing gastric fluid concentration, decreasing the number of ulcers, decreasing the ulcer index and increasing gastric pH. Based on the description above, it can be concluded that the ethanol extract of avocado leaves has an anti-inflammatory effect in reducing gastritis.

Transformation of patchouli alcohol to \u03b2-patchoulene by gastric juice: \u03b2-patchoulene is more effective in preventing ethanol-induced gastric injury

Pogostemonis Herba is a functional food approved in Asian countries. Its major constituent, patchouli alcohol (PA), possesses a gastroprotective effect and is reported to transform into β-patchoulene (β-PAE) under acidic conditions. To investigate whether β-PAE, the metabolite of PA, has a protective effect on the gastrointestinal tract, the formation of β-PAE by gastric juice and the anti-ulcerogenic potential of β-PAE against ethanol-induced gastric injury were evaluated. The Results indicated that PA was converted to β-PAE by rat gastric juice. Additionally, β-PAE was significantly better than PA at reducing the area of gastric ulcer. The overproduction of malondialdehyde, tumour necrosis factor-α, interleukin (IL)-1β, IL-6, Fas, FasL and caspase-3 was markedly inhibited by β-PAE while the underproduction of superoxide dismutase, glutathione and catalase was significantly improved. β-PAE also regulated the NF-κB and ERK1/2 signalling pathways. Our findings suggest that β-PAE has potential therapeutic efficacy for antiulcer treatment.

Study on stability of major pharmaceutical ingredients of Vladimiriae Radix before and after being roasted in artificial gastric juice, artificial intestinal juice and isolated rat gastric, intestinal or colonic incubation juice

To study the stability of costunolide (COS) and dehydrocostus lactone (DEH) of Vladimiriae Radix before and after being roasted in artificial gastric juice, artificial intestinal juice and isolated rat gastric, intestinal or colonic incubation juice. The HPLC method was used for the determination of the mass concentration of COS and DEH Vladimiriae Radix before and after being roasted artificial gastric juice, artificial intestinal juice and isolated rat gastric, intestinal or colonic incubation juice. The samples were incubated with isolated rat stomach, small intestine; colon was used to study physical adsorption, absorption or degradation parameters. COS of Vladimiriae Radix before or after being roasted was unstable in artificial gastric juice, with the average degradation constants as 0.758 0 and 0.531 1. Having been roasted, it showed an increasing stability with a significant difference (P < 0.01). Both of COS and DEH of Vladimiriae Radix before or after being roasted showed high adsorption, uptake or degradation (2 h), and it had significant difference between different parts. COS was unstable in artificial gastric juice (unprocessed Vladimiriae Radix has a higher degradation rate). Isolated rat stomach, small intestine, colon can adsorb, take, degrade COS and DEH of Vladimiriae Radix before or after roasting process obviously and differently. It provides basis for studies on the absorption mechanisms of effective ingredients of Vladimiriae Radix before and after being roasted.

Calcium [13C]carbonate breath test for quantitative measurement of total gastric acid in rats

Objective. A traditional measurement of gastric acid, involving nasogastric intubation of stomach and acid suction, has been suggested as a gold standard. However, this causes the patient discomfort and cost increase, and is ‘time-consuming’. Material and methods. A calcium [13C]carbonate (Ca13CO3) breath test was carried out in rats without or with concomitant drugs omeprazole (OMP) and pentagastrin (PG) known as an inhibitor and an inducer of acid, respectively. This test was aimed at evaluating a correlation between the breath response and the total amount of gastric acid. To search for an absorption pathway of 13CO2 gas produced by the reaction of Ca13CO3 with hydrochloric acid in the stomach of rats, we compared the breath responses after intra-gastric administration of 13CO2 gas and sodium [13C]bicarbonate (NaH13CO3). Results. A linear relationship of the breath parameter (breath-Cmax) with the dose of Ca13CO3 was obtained in the range of 4–200 µmol/kg. However, theses parameters were saturated at >200 µmol/kg. The direct correlation between the breath-Cmax and the total amount of gastric acid in rats with or without OMPs or PG (r = 0.994) demonstrated that the change in breath response is an accurate or sensitive indicator of the total amount of gastric acid. 13CO2 gas generated in the rat stomach was likely to diffuse across the stomach wall as 13CO2 gas directly into the blood plasma. Conclusions. The present study showed that Ca13CO3 breath test is a good tool to accurately predict the total amount of gastric acid.

α2-Adrenoceptor-mediated Inhibitory and Excitatory Effects of Detomidine on Rat Gastric Acid Secretion

The effects of the selective alpha 2-adrenoceptor agonist detomidine on gastric acid secretion from pylorus-ligated and stomach-perfused rats have been investigated. In pylorus-ligated rats i.p. injection of detomidine markedly inhibited acid secretion, this effect being prevented by yohimbine or idazoxan. Under the same conditions, idazoxan significantly increased secretion in a dose-independent fashion. In non-vagotomized and vagotomized stomach-perfused rats i.p. detomidine stimulated acid secretion: this excitatory effect was antagonized by idazoxan. The present results suggest that both inhibitory and excitatory gastric secretory effects of detomidine are mediated by alpha 2-adrenoceptors on cholinergic and adrenergic nerves, respectively. The stimulant activity of idazoxan on gastric secretion from pylorus-ligated rats may be interpreted in terms of increased excitatory vagal tone following the blockade of inhibitory alpha 2-adrenoceptors.

Transfer and distribution of amoxicillin in the rat gastric mucosa and gastric juice and the effects of rabeprazole

To investigate the distribution of amoxicillin in the gastric juice and gastric mucosa of rats and to investigate the effects of proton pump inhibitor rabeprazole on amoxicillin concentrations in various compartments. One hundred and sixty anesthetized rats were divided into five groups, and given intravenously different doses of amoxicillin or amoxicillin and rabeprazole. The pH value and volume of gastric juice was aspirated were measured and separated gastric mucosa was homogenized. The concentrations of amoxicillin in the plasma, gastric juice and gastric mucosa were measured by high performance liquid chromatography (HPLC). The maximum concentrations of amoxicillin in gastric juice and gastric mucosa were significantly lower than those in plasma (P<0.001). Concentrations in the glandular stomach mucosa were higher than those in the forestomach mucosa. Rabeprazole did not significantly change the pharmacokinetic parameters of amoxicillin in the plasma and did not alter gastric antibiotic clearance or the gastric transfer fraction of amoxicillin in gastric juice. However, rabeprazole did increase the amoxicillin concentration and pH value in gastric juice and reduced the volume of the gastric juice. Amoxicillin could penetrate the gastric mucosa and achieve therapeutic concentrations at the target site after transfer from the blood to the stomach. Rabeprazole increased the amoxicillin concentration in gastric juice by decreasing the gastric juice volume but did not affect its concentration in blood or gastric mucosa.

Effects of Achillea wilhelmsii on rat′s gastric acid output at basal, vagotomized, and vagal-stimulated conditions

Background:Achillea is a plant widely used in traditional medicine for gastrointestinal disorders. There are some reports on gastrointestinal effects of Achillea, such as antiulcer, antibacterial, hepatoprotective, choleretic, and antispasmodic. To investigate the effects of aqueous–ethanol extract of Achillea wilhelmsii on rat’s gastric acid output in basal, vagotomized (VX), and vagal-stimulated conditions.Materials and Methods:24 male Wistar rats were randomly divided into 2 groups: control and test. Gastroduodenostomy was performed for each rat. Gastric content was collected for 30 min by washout technique. One milliliter of 3 doses (0.5, 1, and 2 mg/kg) was introduced into the stomach of each rat in the test group and the same volume of saline was used in the control group. Total titratable acid was measured by a titrator.Results:The extract inhibited acid output significantly in basal condition by 1 and 2 mg/kg doses (P < 0.05) but in VX condition this inhibitory effect on acid output disappeared and the 1 and 2 mg/kg doses increased acid output significantly (P < 0.05 and P < 0.001, respectively). The extract showed a reduction in the acid output in vagal-stimulated condition by 1 and 2 mg/kg doses, which were not statistically significant.Conclusion:These results showed an inhibitory effect of A. wilhelmsii extract on acid output in basal condition. The inhibitory effect of the extract was exerted via gastric vagal parasympathetic nerve.

PERIPHERAL DOPAMINE D2‐LIKE RECEPTORS HAVE A REGULATORY EFFECT ON CARBACHOL‐, HISTAMINE‐ AND PENTAGASTRIN‐STIMULATED GASTRIC ACID SECRETION

It has been documented that dopamine, an important regulator of gastric function in the brain-gut axis, has an inhibitory effect on the gastric acid secretion. It has also been suggested that dopamine D1, D2 and D5 receptor proteins are present in the gastrointestinal tract from the stomach through to the distal colon. Therefore, we hypothesized that peripheral D2 receptors may be involved in the control of stimulated gastric acid secretion. To address this question, we examined the effect of quinpirole, a selective D2 receptor-like agonist, and domperidone, a peripheral D2 receptor antagonist, on rat gastric acid secretion. Quinpirole (0.0001-0.5 mg/kg, i.p.) was administered simultaneously with intravenous infusions of histamine, pentagastrin, and carbachol. In some experiments, domperidone (3 and 7 mg/kg) was administered 30 min before quinpirole injection. We found that intraperitoneal injection of quinpirole (0.0001-0.5 mg/kg) suppressed stimulated gastric acid secretion induced by histamine (0.08 mg/100 g per h), pentagastrin (1 microg/100 g per h) and carbachol (4 microg/100 g per h) in a dose-dependent manner. This inhibitory effect of quinpirole persisted until the end of the experiments (90-120 min) and was completely suppressed by domperidone (7 mg/kg). In conclusion, the results of the present study suggest that peripheral D2-like receptors have an inhibitory effect on histaminergic-, pentagastrin- and cholinergic-stimulated gastric acid secretion. This inhibitory effect may be mediated by enteric dopaminergic neurons and/or non-neuronal membranes.

Dose-independent pharmacokinetics of clindamycin after intravenous and oral administration to rats: Contribution of gastric first-pass effect to low bioavailability

The pharmacokinetic parameters of clindamycin were evaluated after intravenous (at doses of 50, 100, and 200 mg/kg) and oral (at doses of 75, 150, and 300 mg/kg) administration of the drug to rats. The first-pass effect of clindamycin was also evaluated after intraportal, intragastric, and intraduodenal administration of the drug at a dose of 150 mg/kg to rats. After both intravenous and oral administration of clindamycin, the pharmacokinetic parameters of the drug were dose-independent. Hence, the extent of absolute oral bioavailability ( F) was also independent of oral doses. After oral administration of clindamycin (150 mg/kg), 7.68% of oral dose was not absorbed up to 24 h and F value was 28.2%. The gastric first-pass effect of clindamycin was 60.7% of oral dose. The first-pass effects of clindamycin in the lung, heart, intestine, and liver were almost negligible, if any, in rats. The low F of clindamycin in rats was mainly due to considerable gastric first-pass effect. Clindamycin was stable in rat gastric juice and various buffer solutions having pHs ranging from 1 to 13. The plasma-to-blood cells partition ratio of clindmaycin was 7.59 in rat blood. The plasma protein binding of clindamycin in rats was 67.5%.

Expression of HSP72 in the gastric mucosa is regulated by gastric acid in rats—Correlation of HSP72 expression with mucosal protection

Background and aimThe real mechanism of adaptive cytoprotection in the gastric mucosa is not well established. In the present study, we investigated the effect of acid suppressing agents on a 72-kDa heat shock protein (HSP72) expression, which is known as endogenous cytoprotective factor, in the gastric mucosa. Also, the association of gastric mucosal protective function against HCl-challenge was compared between HSP72-induced and -reduced group. Materials and methodsExpression of HSP72 was measured by Western blotting in the gastric mucosa before and after administration of famotidine or omeprazole. The gastric mucosal protective function against 0.6N HCl was compared between control group and HSP72-reduced group. Also, the effect of increased expression of gastric HSP72 by additional administration of zinc sulfate or zinc l-carnosine, which is known as HSP72-inducer, on mucosal protective function was studied. ResultsHSP72 expression in the gastric mucosa was reduced by acid suppressing agents. The lowest expression level of HSP72 was observed 12h (famotidine, H2-receptor antagonist) or 48h (omeprazole, proton pump inhibitor) after administration. The gastric mucosal protective ability against 0.6N HCl was also reduced when HSP72 expression was decreased by famotidine or omeprazole. This phenomenon was reversed by HSP72 induction by additional administration of zinc derivatives. ConclusionOur results might indicate that the expression of HSP72 in the gastric mucosa is physiologically regulated by gastric acid, and that HSP72 induction could be important in view of mucosal protection especially when HSP72 expression is reduced by administration of acid suppressing agents such as proton pump inhibitor or H2 receptor antagonist.

Effects of Cannabinoid Receptor Agonists on Rat Gastric Acid Secretion: Discrepancy Between In Vitro and In Vivo Data

The effects of the cannabinoid (CB)-receptor agonists WIN55,212-2 and HU-210 and the selective CB(1)-receptor antagonist SR141716A were tested on in vitro and in vivo acid secretion assays from the rat. In the isolated gastric fundus from immature rats, WIN55,212-2 (0.001-30 microM), HU-210 (0.001-10 microM), or SR141716A (0.1-10 microM) did not change the basal acid output or acid responses to histamine, pentagastrin, or electrical field stimulation. HU-210 (0.3 micromol/kg, intravenously) inhibited the acid response to pentagastrin in anesthetized adult, young, or immature rats with lumen-perfused stomachs; moreover, HU-210 reduced vagally induced acid secretion in adult animals, its antisecretory effect being reversed by SR141716A (0.65 micromol/kg, intravenously). In vitro and in vivo data indicate that CB(1) receptors are not located on parietal cells but, rather, on vagal pathways (possibly at preganglionic sites) supplying the gastric mucosa. The lack of effect of CB-receptor ligands in vitro cannot be ascribed to the use of immature rats, since HU-210 inhibited stimulated acid secretion in vivo, irrespective of the animal age.

Quantification of clarithromycin, its 14-hydroxy and decladinose metabolites in rat plasma, gastric juice and gastric tissue using high-performance liquid chromatography with electrochemical detection

A rapid, selective and sensitive HPLC assay has been developed for the simultaneous analysis of clarithromycin, its 14-hydroxy-clarithromycin metabolite, and its decladinose acid degradation product, in small volumes of rat gastric juice aspirate, plasma and gastric tissue. Sample were extracted with n-hexane/2-butanol (4:1) and the internal standard was roxithromycin. A Kromasil ODS 5 μm (75×4.6 mm I.D.) column was used with a mobile phase consisting of acetonitrile/aqueous phosphate buffer (pH 7, 0.086 M) (45:55 v/v). The column temperature was 30 °C and coulometric detection was used at 850 mV using a screen voltage of 600 mV. The analysis time was less than 8 min. The limits of quantitation for clarithromycin, 14-OH clarithromycin and decladinose clarithromycin were 0.15 μg ml −1 or lower in plasma (0.05 ml); 0.16 μg ml −1 or lower in gastric juice (0.2 ml); and 0.51 μg g −1 or lower for gastric tissue (0.25 g). The method was linear up to at least 20.3, 15.4 and 12.5 μg ml −1 for clarithromycin, 14-OH-clarithromycin and decladinose, respectively, in gastric juice aspirate and plasma and up to 40.6, 30.9 and 25.0 μg g −1 in gastric tissue. The assay was applied to the measurement of clarithromycin, 14-OH-clarithromycin and, for the first time, decladinose clarithromycin in pharmacokinetic studies of gastric transfer of clarithromycin in individual rats.

Role for central ghrelin in food intake and secretion profile of stomach ghrelin in rats.

Ghrelin, a 28-amino-acid peptide, has recently been isolated from the rat stomach as an endogenous ligand for the GH secretagogue receptor. We have reported previously that central or peripheral administration of ghrelin stimulates food intake, and the secretion of GH and gastric acid in rats. In the present study, we investigated how much endogenous centrally released ghrelin is involved in the control of food intake and body weight gain. We also examined the profile of ghrelin secretion from the stomach by RIA using two kinds of anti-ghrelin antiserum, one raised against the N-terminal ([Cys(12)]-ghrelin[1-11]) region and one raised against the C-terminal ([Cys(0)]-ghrelin [13-28]) region of the peptide. The former antibody recognizes specifically ghrelin with n- octanoylated Ser 3 (acyl ghrelin), and does not recognize des-acyl ghrelin. The latter also recognizes des-acyl ghrelin (i.e. total ghrelin). Intracerebroventricular treatment with the anti-ghrelin antiserum against the N-terminal region twice a day for 5 days decreased significantly both daily food intake and body weight. Des-acyl ghrelin levels were significantly higher in the gastric vein than in the trunk. Either fasting for 12 h, administration of gastrin or cholecystokinin resulted in increase of both acyl and des-acyl ghrelin levels. The ghrelin levels exhibited a diurnal pattern, with the bimodal peaks occurring before dark and light periods. These two peaks were consistent with maximum and minimum volumes of gastric content respectively. These results suggest that (1) endogenous centrally released ghrelin participates in the regulation of food intake and body weight, (2) acyl ghrelin is secreted from the stomach, (3) intestinal hormones stimulate ghrelin release from the stomach, and (4) regulation of the diurnal rhythm of ghrelin is complex, since ghrelin secretion is augmented under conditions of both gastric emptying and filling.

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.

Evaluation of the pharmacological activity of extracts from Amomi Semen on the gastrointestinal tracts

We have investigated the effects of methanolic and alcoholic extracts from Amomi Semen on gastric secretion, as well as gastrointestinal propulsion or the prokinetic activities. The methanolic extract from Amomi Semen dose dependently decreased the volume output, acid output, and pepsin output in rat's gastric juice with increasing pH value, while the alcoholic extract had no influence on basal gastric acid secretion. Furthermore, the alcoholic extract improved the l-dopa to induce a delay of gastrointestinal transit in mice, while the methanolic extract did not improve it. However, both extracts had no influence on gastrointestinal transit in intact mice. These results suggest that Amomi Semen has an inhibitory effect on gastric acid secretion and that it has effects as the gastrointestinal prokinetics rather than propulsion. The present study pharmacologically elucidates a belief that Amomi Semen has been used in Chinese medicine for the treatment of gastrointestinal dyspepsia, which includes hyperchlorhydria, stomachache, abdominal distention, anorexia, gastric atony, etc.

Role of central glutamate receptors, nitric oxide and soluble guanylyl cyclase in the inhibition by endotoxin of rat gastric acid secretion.

1. This study examines the role of a central pathway involving glutamate receptors, nitric oxide (NO) and cyclic GMP in the acute inhibitory effects of low doses of peripheral endotoxin on pentagastrin-stimulated acid production. 2. Vagotomy or intracisternal (i.c.) microinjections of the NO-inhibitor, N(G)-nitro-L-arginine methyl esther (L-NAME; 200 microg rat(-1)) restored acid secretory responses in endotoxin (10 microg kg(-1), i.v.)-treated rats. 3. The acid-inhibitory effect of i.v. endotoxin (10 microg kg(-1), i.v.) was prevented by prior i.c. administration of the NMDA receptor antagonists, dizocilpine maleate (MK-801; 10 nmol rat(-1)) and D-2-amino-5-phosphono-valeric acid (AP-5; 20 nmol rat(-1)), or the AMPA/kainate antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX; 10 nmol rat(-1)). However, the competitive metabotropic glutamate receptor antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG; 20 - 1000 nmol rat(-1)) did not antagonize the effects of endotoxin. 4. I.c. administration of L-glutamate (0.1 nmol rat(-1)) inhibited pentagastrin-stimulated gastric acid secretion. Coadministration with L-NAME (200 microg rat(-1)) prevented the inhibition of gastric acid secretion by the aminoacid. 5. I.c. administration of 1H-[1,2, 4]Oxazodiolo[4,3-a]quinoxalin-1-one (ODQ; 100 nmol rat(-1)), a soluble guanylyl cyclase (sGC) blocker, reversed the hyposecretory effect of endotoxin. 6. I.c. administration of the cyclic GMP analogue 8-Bromoguanosine-3,5-cyclic monophosphate (8-Br-cGMP; 100 - 300 nmol rat(-1)) reduced gastric acid production in a dose-dependent manner. 7. We conclude that central NMDA and AMPA/kainate receptors are involved in the acid inhibitory effect of peripherally administered endotoxin. This central pathway involves synthesis of NO, which acts on the enzyme sGC.

Role of CB 1 cannabinoid receptors in the regulation of rat gastric acid secretion

Role of CB 1 cannabinoid receptors in the regulation of rat gastric acid secretion

Synthesis of nitric oxide in the dorsal motor nucleus of the vagus mediates the inhibition of gastric acid secretion by central bombesin.

1. Central administration of bombesin inhibits gastric acid production independently of the centrally or peripherally-acting stimuli employed. This study evaluates the role and location of the cerebral nitric oxide (NO) implicated in the inhibitory effect of central bombesin on in vivo rat gastric acid secretion, as induced by distension with 15 cm H2O, insulin (0.75 u.i. kg-1 i.p.) TRH (1.2 microg kg-1, i.c.) or pentagastrin (100 microg kg-1, i.p.). 2. The acid-inhibitory effect of i.c. bombesin (40 ng kg-1) was prevented by prior administration of L-NAME (80 microg kg-1) in the dorsal motor nucleus of the vagus (DMN). This dose of L-NAME when administered into the nucleus of the tractus solitarious (NTS) did not influence the effects of bombesin. Administration of L-arginine (400 microg kg-1) into the DMN restored the acid-inhibitory effect of i.c. bombesin in animals treated with L-NAME. 3. Microinjection of bombesin (12 ng kg-1) into the paraventricular nucleus of the hypothalamus (PvN) inhibits acid secretion stimulated by pentagastrin. This inhibitory effect was prevented by a previous injection of L-NAME (80 microg kg-1) into the DMN. 4. The release of NO in the DMN following i.c. administration of bombesin was confirmed by in vivo electrochemical detection. 5. Administration by microdialysis in the DMN of the NO-donor SNAP (25 mM in 1.5 microl min-1) into the DMN inhibits pentagastrin-stimulated gastric acid secretion. 6. The present study suggests that nNOS-containing neurons in the DMN have an inhibitory role in the control of gastric acid responses.

Centrally Applied Nitric Oxide Donors Inhibit Vagally Evoked Rat Gastric Acid Secretion: Involvement of Sympathetic Outflow

Centrally Applied Nitric Oxide Donors Inhibit Vagally Evoked Rat Gastric Acid Secretion: Involvement of Sympathetic Outflow

Centrally applied nitric oxide donors inhibit vagally evoked rat gastric acid secretion: involvement of sympathetic outflow.

ntracerebroventricularly (i.c.v.) administered nitric oxide (NO) donors, 3-morpholinosydnonimine (SIN-1) (100-500 microg/animal) and sodium nitroprusside (SNP) (100-250 microg/animal) dose-dependently inhibited the rat gastric acid secretion evoked by vagal stimulation at 3 Hz. Furthermore, the inhibitory effect of SIN-1 (250 microg/animal) was more marked and its onset was more rapid than that of SNP (250 microg/animal). The SIN-1 (250 microg/animal)-induced antisecretory effect was abolished by both splanchnicotomy and phentolamine (5 mg/kg, i.m.), and also by indomethacin (500 microg/animal, i.c.v.). These results suggest that i.c.v. administered NO donors inhibit vagally evoked gastric acid secretion by activation of central sympathetic outflow. Central prostaglandin is probably implicated in this NO-mediated antisecretory effect.