EFFECT of AUTONOMIC DRUGS on the STRESS INDUCED ACUTE GASTRIC (5 Mg and 10 Mg/Kg), ULCERATION in RAT All the Drugs We

Volume 20 Number 3

salfate (1 mg and 10 m mine salicylate (0.1 m EFFECT OF AUTONOMIC DRUGS ON THE STRESS INDUCED ACUTE GASTRIC (5 mg and 10 mg/kg), ULCERATION IN RAT All the drugs we

M.S. MANEKAR terms of salts.

Department of Pharmacology, Miraj Medical College, Miraj (Maharashtra)

It was observed t

Summary: Stress ulcers were induced by subjecting rats to forced immobilisation and cold gastric ulceration and s (4° to 7°C) for 4 hrs. The nature of drugs which afford varying degrees of protection against such the glandular portion 0 ulceration, bring out the complexity of the factors involved in the study of pathogenesis of acute gastric ulceration due to stress.

Key words: stress restraint acute gastric ulceration

INTRODUCTION

Acute gastric ulceration and haemorrchage are common in a variety of clinical situations. The pathogenesis of these ulcerations is not clearly understood (2). Involvement of sympathetic nervous system in the pathogenesis of acute gastric ulceration has been reported (2,4,5.). The object of the present work was to study the effect of some autonomic drugs in prevention of stress induced acute gastric ulceration.

MATERIALS AND METHODS

Albino rats of either sex weighing between 150 to 300 gm were included in this study. Animals were fasted for 24 hrs prior to the experiment. Only tap water was provided as libitum during this period. Animals were subjected to restraint and cold stress as reported by Senay and Levine (3).

Animals were immobilised by placing them individually in small, wide-mouthed glass bottles which provided adequate accommodation but did not allow any movement. These bottles were kept at 4° to 7°C in the refrigerator for 4 hrs. Fig. I: Animals were sacrificed after 4 hrs by a blow on the head and by cutting both the carotid arteries. Abdominal cavity was opened and the stomach was quickly removed. It was opened Of the various drug along the greater curvature. The mucosa was washed with normal saline at room temp. and pine afforded varying de was inspected for the presence of ulceration and haemorrhage with the help of a magnifying glas Consolidated results are

Lesions were defined as erosions of the gastric mucosa at least I mm in diameter, the edges Propranolol in 5 of which were sharply demarcated and their bases were red or black. Groups of animals were showed adequate prote treated with one of the following drugs 30 min before exposure to stress. Reserpine was given 24 hrs before exposure to stress. Drugs used were adrenaline tartrate Cl and 10 Il-g/kg), atropine Carbachol, physo induced gastric ulcerati Volume 20 Stress Induced Acute Gastric Ulceration 161 Number 3

salfate (1 mg and 10 mg/kg), ephedrine hydrochloride (1 mglkg), carbachol (1 mgjkg), physostigmine salicylate (0.1 mg/kg), tolazoline hydrochloride (10 mgjkg), propranolol hydrochloride UCED ACUTE GASTRIC (5 mg and 10 mg/kg), reserpine (1 mgjkg), tyramine (1 mgjkg).

All the drugs were administered by intraperitoneal injection. Doses are mentioned in terms of salts.

Miraj (Maharashtra) RESULTS It was observed that 83.30/0of rats subjected to cold and restraint for 4 hrs developed acute

reed immobilisation and cold gastric ulceration and sometimes haemorrhage (Fig. I). Acute gastric ulceration was observed in ees of protection against such the glandular portion only. Perforation of the stomach was not observed in any of the animals. ofpathogenesisof acute gastric

ulceration

variety of clinical situations . . Involvement of sympathetic s been reported (2,4,5.). The c drugs in prevention of stress

were included in this study. water was provided as libitum d stress as reported by Senay

all, wide-mouthed glass bottles ovement. These bottles were

Fig. 1: Showing stress induced acute gastric ulceration in grandular part of the stomach. nd by cutting both the carotid ickly removed. It was opened Of the various drugs used, reserpine, tolazoline, propranolol, ephedrine, tyramine and atro- al saline at room temp. and pine afforded varying degrees of protection against restraint and cold induced gastric ulceration. the help of a magnifying glass. Consolidated results are shown in Table 1.

t 1 mm in diameter, the edges Propranolol in 5 mglkg dose did not afford any protection, but in a dose of 10 mgjkg, k. Groups of animals were showed adequate protection. stress. Reserpine was given Carbachol, physostigmine and adrenaline did not show any protective action against stress ate (I and 10 II-gjkg), atropine induced gastric ulceration. Volume 20 162 Manekar July-September 1976 Number 3 Ind. J. Physiol. Pharmac, TABLEI : Showing the effect of drugs on stress induced ulceration. Atropine produ cated by our results an Sr. Treatment No. of rats No. of rats degree of protection wh No. used showing Percentage U+H gastric ulceration, als

1. Control 60 50 83.3 pathogenesis of the str 2. Atropine Sulphate 20 3 15.0 I mg./kg

3. Atropine Sulphate 1. Brodie, D.A. and H. 10 mg/kg 10 10.0 restraint technic. Gas 2. Djahanguiri, B., H.L. -l. Carbachol 10 10 100.0 Img/kg restraint ulcer in Rats. 3. Senay, E.C. and R.J. 5. Physostigmine Salicylate 10 10 100.0 in rats. _Proc. s«. Exp. 0.1 mg/kg 4. Sethbhakdi, S. and C. 15 : 261-270, 1970. 6. Adrenaline Tartrate 20 16 80.0 la mg/kg 5. Sethbhakdi, S.,J.L.A. the etiologic mechanis 7. Reserpine 5 o 0.0 Img/kg 8. Propranolol Hydrochloride la 2 20.0 10 mg/kg

9. Tolazoline Hydrochloride la 2 20.0 10 mg/kg

10. Ephedrine Hydrochloride 10 o 0.0 l.ng/kg 11. Tyramine 10 o 0.0 I mg/kg

U +H = Ulceration and Haemorrhage.

DISCUSSION

The results show that synergism between restraint and cold is quite effective in producing acute gastric ulceration and are in agreement with those reported by Senay and Levine (3).

Reserpine, a well known ulcerogenic drug, which depletes the catecholamine stores in the body, effectively prevented acute stress induced ulcers. This paradoxical action may be purely due to its tranquillising action. Similarly, the alpha-adrenergic receptor blocking agent (Tolazoline) and beta-adrenergic receptor blocking agent, (propranolol 10 mgjkg) also afforded considerable degree of protection against stress induced ulceration. These results indicate the possible involvement of the sympathetic nervous system in the pathogenesis of stress induced acute gastric ulceration, and are in agreement with those of Djahanguiri et al.(2). Propranolol in smaller doses (5 mg/kg) however was quite ineffective. The indirectly acting sympathomimetic amines like ephedrine and tyramine also exhibited the protective action against stress induced ulceration. Their mode of action is not clear from this study, and may be related to a purely local vasocons- trictor action. Stress Induced Acute Gastric Ulceration 163 July-September 1976 Ind. J. PhysioI. Pharmac. Atropine produced well marked protection against the stress induced ulceration, as indi- ration. catedby our results and Brodie and Hanson (1). The fact that atropine afforded a significant degreeof protection while carbachol and physostigmine were ineffective against the stress induced Percentage gastric ulceration, also substantiate the involvement of cholinergic mechanisms in" the

50 83.3 pathogenesis of the stress induced ulceration. I ' 3 15.0 REFERENCES

I. Brodie, D.A. and H.M. Hanson, A study of the factors involved in the production of gastric ulcers by the 10.0 restraint technic. Gastroenterology, 38 : 353-360 1960. 2. Djahanguiri, B., H.L. Taulin and L. Landsberg. Increased sympathetic activity in the pathogenesis of 10 100.0 restraint ulcer in Rats. J. Pharmacol., 184 : 163-168, 1973. 3. Senay, E.C. and R.J. Levine. Synergism between cold and restraint for. rapid production of stress ulcers IO 100.0 in rats..!:Proc. Soc. Exp. Bioi. Med., 124 : 1221-1223, 1967. 4. Sethbhakdi, S. and C.J. Pfeiffer. Gastric mucosal ulceration following vasoactive agents. Amer. J. Dig-Dis., 15 : 261-270, 1970. . 80.0 16 5. Sethbhakdi, S., J.L.A. Roth and C.]. Pfeiffer. Gastric mucosal ulceration after epinephrine. A study of the etiologic mechanism. Ibi d, 15 : 1055-1065, 1970. o 0.0

2 20.0

o 0.0

quite effective in producing Senay and Levine (3). catecholamine stores in the cal action may be purely due blocking agent (Tolazoline) ) also afforded considerable Its indicate the possible in- stress induced acute gastric Propranolol in smaller doses mpathomimetic amines like t stress induced ulceration. to a purely local vasocons-