Detrusor hyperreflexia induced by intravesical instillation of xylene in conscious rats.

Intravesical instillation of xylene (30-50%) produced detrusor hyperreflexia characterized by a decrease in both the bladder capacity (time to micturition in the cystometrogram) and the urine volume in conscious rats placed in a restraining cage. At this time, the bladder tissue showed evidence of experimental cystitis with degradation of the epithelium and edema and hemorrhage in the submucosa, and a slight increase in the content of prostaglandin E2, which stimulated directly and/or indirectly capsaicin-sensitive sensory fibers. In addition, the bladder exhibited high amplitude spontaneous activity, but the bladder contractions induced by acetylcholine, substance P, prostaglandin E2 and capsaicin were not changed following intravesical instillation of xylene. In these hyperreflexic rats, atropine suppressed the amplitude of the micturition contraction and morphine increased the bladder capacity at similar doses as in sham-treated rats, while thiopental and indomethacin increased the bladder capacity at lower doses than in sham-treated rats. These findings indicated that intravesical instillation of xylene had produced detrusor hyperreflexia in conscious rats, and that the detrusor hyperreflexia is thought to be a useful model for evaluating the effect of a newly-developed agent on bladder function.     

A new method for producing urinary bladder hyperactivity using a non-invasive transient intravesical infusion of acetic acid in conscious rats

INTRODUCTION: Animal models that closely resemble the pathophysiology of human overactive bladder are important for evaluating novel therapeutics to treat the disorder. We established a non-invasive hyperactive bladder model that is sensitive to anti-muscarinic drugs and without bladder inflammation. METHODS: Acetic acid solution was infused into the bladder for 5 min via the urethral orifice without any surgical procedures under isoflurane anaesthesia. After washing the bladder with saline, voiding frequency (VF) and total urine volume were determined for 9 h under conscious conditions. RESULTS: Infusion of a 0.5% acetic acid solution caused a significant increase in VF, without influencing total urine volume or inducing significant histopathological inflammatory alterations in the bladder urothelium. Oral administration of oxybutynin (3 and 10 mg/kg) significantly ameliorated increases in VF induced by 0.5% acetic acid. Infusion of 0.75% acetic acid induced intensive urinary inflammation and a decrease in total urine volume as well as an increase in VF. Oral treatment with oxybutynin (10 mg/kg) did not significantly improve the increased VF due to 0.75% acetic acid. Acetic acid (0.5%) infusion evoked bladder hyper-responsiveness whether applied at night or during the day. However, VF was increased more by the nighttime application of acetic acid, while there were no significant differences in basal levels of VF between daytime and nighttime. DISCUSSION: In this study, the non-invasive rat urinary hyperactive bladder model indicated minimizes the secondary effects of experimental procedures such as surgical operations and anesthesia on bladder function and is sensitive to oxybutynin. Thus, the model may be useful for investigating novel therapeutics for OAB treatment.     

Effect of N-acetylcysteine on colitis induced by acetic acid in rats.

(1) To verify the proposed role of reactive oxygen species (ROS) in ulcerative colitis, the effect of an antioxidant N-acetylcysteine (NAC) was studied in acetic acid (AA)-induced colonic inflammation. (2) Depending on the dose used, NAC administered intracolonically was found to reduce the extent of colonic damage, along with a decrease in myeloperoxidase (MPO) activity, colonic wet weight and wet/dry weight ratio. (3) NAC attenuated the enhanced vascular permeability and prevented the depletion of colonic reduced glutathione (GSH) caused by AA administration. (4) The findings indicate that NAC may prove beneficial in the treatment of colitis.     

胃力康颗粒对实验性胃溃疡模型大鼠的影响

目的:观察胃力康颗粒对实验性胃溃疡大鼠的影响,探讨胃力康颗粒对实验性胃溃疡大鼠溃疡愈合的作用。方法:制备大鼠胃溃疡模型,大鼠随机分成正常组、模型组、法莫替丁对照组和胃力康治疗组,术后连续给药7d,测定大鼠血清中一氧化氮(NO)、超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果:与模型组比较,胃力康组能显著提高大鼠血清中NO和SOD含量,降低MDA的含量,差异均有统计学意义(P<0.05)。结论:胃力康对大鼠胃溃疡的保护性治疗作用,其机制可能与提高血清NO和SOD含量,降低MDA含量有关。     

Exacerbation of acetic acid ulcer induced by non-steroidal anti-inflammatory drugs in rats

The influences of non-steroidal anti-inflammatory drugs (NSAID) on acetic acid ulcer were examined in rats. NSAID used in this study were aspirin (ASP, 200 mg/kg), indomethacin (IND, 2 mg/kg) and phenylbutazone (PHE, 100 mg/kg). These NSAID were administered consecutively for 5 days once a day at the early stage of the ulcer. Eleven days after the ulceration, suppression of the healing was observed in rats treated with all of the NSAID. In the rats treated with either ASP or IND, a delay of healing was observed not only 11 days after ulceration, but also 16 days after ulceration. The ulcer index in rats treated with either ASP or IND 16 days after ulceration was greater than that at 11 days after ulceration. Further studies were performed regarding the progressive change of mucosal hexosamine content, gastric secretion and gastric emptying during the healing process of the ulcer. It was found that the increase of hexosamine plays an important role in the healing of the ulcer and that a durable fall in hexosamine content was related to the remarkable exacerbation of ulcer induced by either ASP or IND. Hypersecretion, back diffusion of hydrogen ion or a delay of gastric emptying cannot be regarded as a cause of the exacerbation of the ulcer.     

Involvement of capsaicin-sensitive neurones in the haemodynamic effects of exogenous vasoactive peptides: studies in conscious, adult Long Evans rats treated neonatally with capsaicin.

1. The regional haemodynamic effects of i.v. bolus injections of bradykinin (0.05 or 0.5 nmol), cholecystokinin (0.175 or 1.75 nmol), substance P (0.01 or 0.1 nmol) and calcitonin gene-related peptide (0.05 or 0.5 nmol) were assessed in conscious, adult Long Evans rats that had been treated neonatally with either capsaicin (50 mg kg-1, s.c.) or vehicle. 2. In vehicle-treated rats, both doses of bradykinin were without effect on blood pressure, but caused tachycardia and hindquarters vasodilatation. Moreover, after the higher dose there were dilatations in the renal and superior mesenteric vascular beds. In capsaicin-treated rats the hindquarters vasodilator effects elicited by both doses of bradykinin were significantly reduced, while the tachycardia and responses in the renal and superior mesenteric vascular beds were unchanged. 3. In vehicle-treated rats, cholecystokinin caused dose-dependent increases in blood pressure accompanied by renal, superior mesenteric and hindquarters vasoconstriction followed, after the higher dose, by a hindquarters vasodilatation. The lower dose produced a tachycardia, while there was a bradycardia followed by a tachycardia after the higher dose. In capsaicin-treated rats, the pressor response, as well as the renal vasoconstrictor effects of cholecystokinin, were greater than in vehicle-treated rats, while the heart rate, superior mesenteric or hindquarters responses were not different. 4. In vehicle-treated rats, substance P produced a dose-dependent depressor response and tachycardia accompanied by dilatations in the renal and hindquarters vascular beds and constriction in the superior mesenteric vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of solifenacin succinate (YM905) on detrusor overactivity in conscious cerebral infarcted rats

Solifenacin succinate [YM905, (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinate] is a novel muscarinic receptor antagonist. We examined the effects of solifenacin and two other muscarinic receptor antagonists, tolterodine and propiverine, on detrusor overactivity in cerebral infarcted rats. Evaluation was done under conscious conditions using cystometry 1 day after middle cerebral artery occlusion. The cerebral infarcted rats showed decreases in bladder capacity and voided volume and an increase in residual volume, but no change in micturition pressure. Solifenacin increased bladder capacity and voided volume at doses of 0.03 mg/kg i.v. or more. Tolterodine increased bladder capacity and voided volume at 0.03 and 0.1 mg/kg i.v., while propiverine increased bladder capacity and voided volume at 1 mg/kg i.v. and at 0.3 and 1 mg/kg i.v., respectively. In contrast, none of the three drugs affected residual volume or micturition pressure. These results suggest that solifenacin may improve detrusor overactivity without causing urinary retention and may be a promising drug in the treatment of patients with overactive bladder syndrome.     

Effects of tiropramide hydrochloride on the isolated detrusor and intravesical pressure of the bladder in situ in rats]

The effects of tiropramide on the isolated detrusor and intravesical pressure of the bladder in situ in rats were compared with those of flavoxate, oxybutynin and terodiline. The IC50 values (x 10(-5) M) of tiropramide for carbachol (CCh)-, K+ (60 mM)-, Ba2+ (10 mM)-, and electrical stimulation-induced contractions were 3.6, 4.2, 5.8, and 2.9, respectively. The four antispasmodics used (2 and 4 mg/kg, i.v., each) abolished the rhythmic bladder contractions in situ in anesthesized rats. Of the four compounds, oxybutynin was most potent and no significant differences were observed between the inhibitory effects of tiropramide, flavoxate and terodiline. The administration of flavoxate (30 and 60 mg/kg) into the duodenum little influenced the rhythmic bladder contractions. Tiropramide, flavoxate, oxybutynin and terodiline (8 and 12 mg/kg, i.v., each) dose-dependently prolonged the time to the volume-evoked micturition reflex, and the activity of tiropramide was not statistically different from those of the other three antispasmodics. Under unilateral pelvic and bilateral hypogastric nerve transection, both of the contractions induced by electrical stimulation of the peripheral and central cut ends of the pelvic nerve were dose-dependently inhibited to the same extent by tiropramide and terodiline. These results suggest that the effects of tiropramide on the function of urinary bladder in rats may be mainly due to direct actions on the smooth muscle, and that tiropramide is more potent than flavoxate and less potent than oxybutynin and terodiline.     

Preventive effect of TRPV1 agonists capsaicin and resiniferatoxin on ischemia/reperfusion-induced renal injury in rats

We evaluated the effect of capsaicin, one of the transient receptor potential vanilloid receptor 1 (TRPV1) agonists, on ischemic acute renal failure (ARF) in rats. Ischemic ARF was induced by occlusion of the left renal artery and vein for 45 minutes followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function in vehicle-treated ARF rats markedly decreased at 24 hours after reperfusion. Treatment with capsaicin (3, 10, and 30 mg/kg, orally) 30 minutes before ischemia dose-dependently attenuated ischemia/reperfusion-induced renal dysfunction. In renal tissues exposed to ischemia/reperfusion, neutrophil infiltration, renal superoxide production, and renal tumor necrosis factor (TNF)-alpha mRNA expression were augmented, but these alterations were attenuated by the treatment with capsaicin. On the other hand, ischemia/reperfusion-enhanced renal interleukin (IL)-10 mRNA expression and plasma concentrations of IL-10 were augmented by treatment with capsaicin in ARF rats. In addition, resiniferatoxin (20 microg/kg, subcutaneous), a more selective and potent TRPV1 agonist, showed a renoprotective effect on ischemia/reperfusion-induced renal injury, in a qualitatively similar way to cases seen with capsaicin. These results demonstrate that TRPV1 agonists prevent ischemia/reperfusion-induced renal dysfunction. These renoprotective effects seem to be closely related to the inhibition of inflammatory response via TRPV1.     

The contribution of capsaicin-sensitive sensory nerves to xylene-induced visceral pain in conscious,freely moving rats

1. Intravesical instillation of xylene (10-100%, dissolved in silicone oil) through a catheter implanted into the bladder of conscious, freely-moving rats produced behavioural effects (licking of lower abdomen or perineal region) suggestive of intense visceral pain, not mimicked by topical application of the irritant on the urethral outlet. 2. The xylene-induced visceral pain was prevented, to the same extent, by systemic desensitization to capsaicin (50 mg/kg s.c.) performed in either adult or newborn rats, as well as by extrinsic bladder denervation (pelvic ganglionectomy), thus indicating the involvement of primary afferents in the bladder wall. 3. Other behavioural responses induced by xylene instillation into the bladder (hind limb hyperextension, grooming) were not affected by systemic capsaicin desensitization in either adult or newborn rats, but were abolished by bladder denervation. 4. Systemic capsaicin desensitization produced an almost complete depletion of substance P-, neurokinin A-like and calcitonin gene-related peptide-like immunoreactivity in the rat urinary bladder. 5. These findings indicate that, in addition to their role in activating reflex micturition, the neuropeptides-containing capsaicin-sensitive sensory nerves of the rat bladder are involved in chemogenic visceral pain.     

The effects of selective cyclooxygenase-2 inhibitors, celecoxib and rofecoxib, on experimental colitis induced by acetic acid in rats

Several mediators may be involved in the pathogenesis of inflammatory bowel disease, as well as in experimental colitis. The present work was conducted to investigate the effects of the two selective cyclooxygenase-2 inhibitors, celecoxib and rofecoxib, on experimentally induced colitis in rats. Rectal instillation of acetic acid was used to induce the colitis. Acetic acid treatment caused haemorrhagic diarrhoea and weight loss in rats. Celecoxib (5 mg/kg) or rofecoxib (2.5 mg/kg), when given twice daily by the oral route, reduced the degree of haemorrhagic diarrhoea and the weight loss produced. In addition, they produced a significant reduction in the degree of colonic injury, the rise in myeloperoxidase (MPO) levels, total nitric oxide synthetase (NOS) activity, platelet-activating factor (PAF), histamine levels and prostaglandin E2 levels. In contrast, there was a significant increase in the levels of reduced glutathione (GSH). Thus, the findings of the present study provide evidence that selective cyclooxygenase-2 inhibitors may be beneficial in patients with inflammatory bowel disease.     

The new experimental ulcerative colitis model in rats induced by subserosal injection of acetic acid

Prostacyclin is an endogeneous eicosanoid synthesized by vascular endothelial cells, and has potent inhibitory effects on platelet adhesion/aggregation and vasoconstriction. However, its therapeutic use is restricted by its extremely short half-life. Beraprost sodium (beraprost) is the first orally active prostacyclin analogue developed by TORAY Industries, Inc. Beraprost possesses a phenol moiety instead of the exo-enol ether moiety, which is the cause of the instability of prostacyclin, and has a modified omega-side chain that contributes to dissociating antiplatelet action from adverse reactions. In 1992, beraprost was approved as a drug for chronic arterial occlusion. Beraprost is now widely used clinically as "Dorner" or "Procylin". The indication for "primary pulmonary hypertension" was also approved in 1999. Recently in Europe, a placebo controlled trial named "Beraprost et Claudication Intermittent-2 (BERCI-2)" was performed, and it was reported that beraprost improved the walking distances of the patients. Beraprost has a variety of biological activities such as antiplatelet effects, vasodilation effects, antiproliferative effects on vascular smooth muscle cells, cytoprotective effects on endothelial cells and inhibitory effects on the production of inflammatory cytokines. On the basis of basic and clinical research, it has been suggested that beraprost is also effective for many intractable diseases. We expect that the relationship between reduced prostacyclin level and these diseases would be clarified and the beneficial effects of beraprost would be demonstrated by controlled clinical trials in the future.     

Azithromycin and erythromycin ameliorate the extent of colonic damage induced by acetic acid in rats

Ulcerative colitis is a common inflammatory bowel disease (IBD) of unknown etiology. Recent studies have revealed the role of some microorganisms in the initiation and perpetuation of IBD. The role of antibiotics in the possible modulation of colon inflammation is still uncertain. In this study, we evaluated the effects of two macrolides, namely azithromycin and erythromycin, at different doses on the extent and severity of ulcerative colitis caused by intracolonic administration of 3% acetic acid in rats. The lesions and the inflammatory response were assessed by histology and measurement of myeloperoxidase (MPO) activity, nitric oxide synthetase (NOS) and tumor necrosis factor alpha (TNFα) in colonic tissues. Inflammation following acetic acid instillation was characterized by oedema, diffuse inflammatory cell infiltration and necrosis. Increase in MPO, NOS and TNFα was detected in the colonic tissues. Administration of either azithromycin or erythromycin at different dosage (10, 20 and 40 mg/kg orally, daily for 5 consecutive days) significantly (P < 0.05) reduced the colonic damage, MPO and NOS activities as well as TNFα level. This reduction was highly significant with azithromycin when given at a dose of 40 mg/kg. It is concluded that azithromycin and erythromycin may have a beneficial therapeutic role in ulcerative colitis.     

Protective effect of embelin against acetic acid induced ulcerative colitis in rats

The aim of the present study is to evaluate the effect of embelin isolated from Embelia ribes on acetic acid induced colitis in rats. Experimental animals received embelin (25 and 50 mg/kg, p.o.) and sulfasalazine (100 mg/kg, p.o.) for five consecutive days before induction of colitis by intra-rectal acetic acid (3% v/v) administration and the treatment continued up to 7 days. The colonic mucosal injury was assessed by clinical, macroscopic, biochemical and histopathological examinations. Embelin treatment significantly decreased clinical activity score, gross lesion score, percent affected area and wet colon weight when compared to acetic acid induced controls. The treatment also reduced significantly the colonic myeloperoxidase activity, lipid peroxides and serum lactate dehydrogenase and significantly increased the reduced glutathione. The histopathological studies also confirmed the foregoing findings. The protective effect may be due to its antioxidant and anti-inflammatory activities.     

The effect of intracerebroventricular injection of histamine in visceral nociception induced by acetic acid in rats

Objective:

This study was designed to investigate the role of brain histamine and H1 and H2 receptors in mediating the central perception of visceral pain in rats.

Materials and Methods:

In conscious rats implanted with a lateral brain ventricle cannula, the effect of intracerebroventricular (i.c.v.) injection of histamine (2.5, 10, and 40 μg), and chlorpheniramine and ranitidine at the same doses of 5, 20, and 80 μg were investigated on visceral pain. Visceral nociception induced by intraperitoneal (i.p.) injection of acetic acid (1 mL, 1%), and the number of complete abdominal wall muscle contractions accompanied with stretching of hind limbs (writhes) were counted for 1 h.

Results:

Histamine at doses of 10 and 40 μg and chlorpheniramine and ranitidine at the same doses of 20 and 80 μg, significantly decreased the numbers of writhes (P < 0.05). Pretreatment with chlorpheniramine and ranitidine at the same dose of 80 μg, significantly prevented histamine (40 μg)-induced antinociception (P < 0.05).

Conclusion:

The results of this study suggest that brain histamine may be involved in modulation of visceral antinociception through both central H₁and H₂receptors.     

Role of capsaicin-sensitive afferent neurons in receptive relaxation induced by gastric distension in rats

We investigated the role of capsaicin-sensitive afferent neurons in receptive relaxation of the rat stomach in response to distension. Under urethane anesthesia, a balloon with barostat was inserted through the pylorus and placed in the forestomach. Isobaric distension was performed in a stepwise increment of 2 mmHg, each lasting for 2 min, while the corresponding intragastric volume was recorded. Gastric distension produced the intraballoon volume in a progressive manner with saturation, suggesting the occurrence of receptive relaxation of the stomach during distension. Intragastric application of capsaicin significantly enhanced the degree of receptive relaxation. The capsaicin-induced enhancement of receptive relaxation was totally abolished by bilateral vagotomy as well as chemical ablation of capsaicin-sensitive afferent neurons. Likewise, the enhanced receptive relaxation in response to stomach distension was also significantly attenuated by pretreatment of the animals with N^G-nitro-L-arginine methyl ester (L-NAME, an inhibitor of nitric oxide (NO) synthase), calcitonin gene related peptide (CGRP)_8-37 (CGRP antagonist), indomethacin and ONO-8711 (EP1 receptor antagonist). These results suggest that capsaicin significantly enhanced the receptive relaxation induced by gastric distention through both vagal nerves and capsaicin-sensitive afferent neurons. This process is intervened by endogenous NO and CGRP in addition to prostaglandins (PGs), and the effect of PGs may be mediated by EP1 receptors. Received 9 October 2006; accepted 10 November 2006     

Protective effect of Periplaneta americana extract in ulcerative colitis rats induced by dinitrochlorobenzene and acetic acid

Context: Periplaneta americana L. (Dictyoptera; Blattaria) has been traditional used to treat ulcers, burns and heart disease in southwestern China. Recent reports indicate that P. americana can be used as an alternative medicine in therapy of ulcerative colitis, but the mechanism involved remains obscure.

Objective: This study investigated the therapeutic effect of P. americana extract (PAE) in rat colitis and elucidated its potential mechanism.

Materials and methods: Dinitrochlorobenzene and acetic acid-induced colitis rat model was applied. Colitis rats were treated with PAE for 10 d and estimated disease activity index daily. Rectal inflammation was assessed by myeloperoxidase activity and histological changes. Another colitis rats were treated with PAE for 4 d, meanwhile gavage with Escherichia coli labelled with green fluorescent protein. Mesenteric lymph nodes, colon, liver, spleen and kidney were harvested for bacteria culture. PAE was suspended in distilled water then partitioned with ethyl acetate and n-butanol to obtain ethyl acetate fraction, n-butanol fraction and water fraction, respectively. Fibroblasts proliferation and collagen accumulation of each fraction was determined.

Results: PAE treatment reduced the severity of colitis and tissue myeloperoxidase accumulation (p?<?0.001). Also, PAE at 80?mg/kg significantly inhibited labelled E. coli from translocating to distant organs, especially to MLN and liver. Additionally, PAE significantly stimulated fibroblasts proliferation (126.9%) and collagen accumulation (130.8%) for 48?h incubation. Among the partitions, ethyl acetate fraction generally had higher fibroblast viability enhanced-activity.

Conclusions: PAE can protect against ulcerative colitis and this protection is attributed to anti-inflammation and fibroblasts viability.     

Effects of phencyclidine on extracellular levels of dopamine, dihydroxyphenylacetic acid and homovanillic acid in conscious and anesthetized rats

Dose-dependent effects of phencyclidine on extracellular levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the neostriatum were studied in both urethane-anesthetized and conscious rats. In vivo microdialysis was used to collect 10 min samples that were analyzed for levels of DA, DOPAC and HVA, using high-performance liquid chromatography with electrochemical detection (HPLC-EC). In both the anesthetized and conscious preparations, 20 mg/kg of phencyclidine produced an increase in extracellular levels of DA, 10 mg/kg resulted in no change, while 1 mg/kg produced a slow decrease. In the anesthetized animals phencyclidine did not have a significant effect on levels of DOPAC or HVA, but in the conscious animals phencyclidine produced a dose-dependent decrease in levels of DOPAC and HVA. The increase in levels of DA could be the result of increased release of DA or inhibition of the uptake of DA. The decrease in levels of DOPAC and HVA, at the 1 mg/kg dose, could result from a decrease in the synthesis of DA that is offset at the 10 and 20 mg/kg doses by opposing mechanisms.     

Effects of capsaicin on intestinal cephalexin absorption in rats

The effects of capsaicin on intestinal cephalexin absorption were investigated by means of in situ single pass perfusion in rats to clarify whether this pungent compound present in spice is a potential factor altering the intestinal drug absorption processes. Under the control condition, cephalexin was absorbed at a rate of 1.16+/-0.08 and 0.90+/-0.06 nmol/min/cm in the jejunum and ileum, respectively. The intestinal cephalexin absorption rate was decreased when capsaicin was dissolved in the perfusate at a concentration of 400 microM, being 0.54+/-0.07 and 0.46+/-0.10 nmol/min/cm in the jejunum and ileum, respectively. The inhibitive effect of capsaicin on intestinal cephalexin absorption was diminished when ruthenium red, a non-selective inhibitor of the transient receptor potential (TRP) cation channels, was intravenously infused into the rat during the experiment. Moreover, when we evaluated the paracellular permeability of cephalexin by utilizing a competitive inhibitor, glycylsarcosine, it was demonstrated that glycylsarcosine-insensitive intestinal cephalexin absorption in the jejunum was increased by 4.5 times in the presence of 400 microM capsaicin. These findings indicate that capsaicin affects both transcellular and paracellular pathways of intestinal cephalexin absorption by interacting with the TRP cation channels in intestinal tissues, in which capsaicin seems to change the transport activity of H+/peptide co-transporter 1 (PEPT1), and to a lesser degree, it seems to alter the paracellular permeability of the intestinal epithelia.     

Healing-promoting action of rhinax with dual action on chronic gastric and duodenal ulcers induced by acetic acid in rats

Healing promoting actions of Rhinax, a multiconstituent herbal preparation, was investigated in chronic gastric and duodenal ulcer models induced by acetic acid in rats and the effects were compared with those of famotidine by gross of histological evaluation. Rhinax markedly promoted the well balanced healing of gastric ulcer at oral does of 25-100 mg/kg x 2 /day, as evidenced by the reduction of ulcer, regeneration of mucosa and proliferation of connecitve tissue. Rhinax caused an increase in gastric mucosa secretion in all the regenerated mucosa around the gastric ulcers. Famotidine failed to promote the healing of gastric ulcers at 100 mg/kg x 2/ day p.o. Rhinax also significantly accelerated the healing of acetic acid -induced duodenal ulcers as well famotidine. These results indicate that Rhinax is characterised by a potent promoting action on the healing of chronic ulcers, suggesting that the increase in gastric mucus secretion might be associated with the antiulcer action of Rhinax in rats.