Details

The gastric mucosal microcirculation in the aetiology of ulcer formation in rat stomachs

by Lau, Hor-keung

Abstract (Summary)
(Uncorrected OCR) i

ABSTRACT

Abstract of thesis entitled liThe gastric mucosal microcirculation in the aetiology of ulcer formation in rat stomachsll

submitted by LAD Hor Keung

for the degree of M~ster of Philosophy (Pharmacology)

at the University of Hong Kong in August, 1980.

The influence of disodium cromoglycate, dexamethasone, bilateral adrenalectomYI bilateral adrenal medullectomy, sodium bicarbonate, papaverine, mepyramine or cimetidine was studied on gastric glandular ulceration, stomach

wall mast cell degranulation and gastric glandular mucosal microcirculatory changes induced by i.p, reserpine or stress (restraint at 4? for 2 h) in rats.

Pretreatment with disodium cromoglycate dosedependently antagonised glandular ulcer formation and stomach mast cell degranulation in reserpine-treated, stressed or methacholine-treated rats. It also antagonised the increase in superficial mucosal microcirculatory

blood volume induced by reserpine or stress. Prior depletion of glandular mucosal mast cells with dexamethasone similarly prevented glandular ulceration and mucosal microvascular changes in reserpine-treated or stressed

animals.

The glandular mucosal mast cell population in

adrenalectomised rats increased in proportion to the number of post-operative days that had elapsed. The mast cell population increased from the 4th postoperative day and was statistically significant from the 7th day onwards. When adrenalectomised rats were given

ii

reserpine on the 4th or 7th post-operative day, glandular ulceration and mucosal microcirculatory volumes were appreciably greater than their sham-operated controls although mast cell degranulation was quantitatively

similar in both groups. Reserpine produced similar

gastric effects when given 48 h after adrenalectomy or adrenal demedullationi these gastric effects were quantitatively comparable in both groups of ablated animals. When used on the 11th or 15th post-adrenalectomy day,

after the glandular mucosal mast cell population was abnormally increased, reserpine induced excessive mast

cell degranulation as well as more intense glandular ulceration and mucosal microcirculatory changes. Comparable findings were made in adrenalectomised rats

exposed to stress on the 15th post-operative day.

Polymyxin B, injected i.p., dose-dependently produced ulcerat?n in the glandular stomach, mast cell degranulation in various layers of the glandular and rumen~l

walls, and increases in the glandular mucosal microcirculatory volume.Ulcer~tion and microvascular changes were substantially reduced by prior depletion of glandular mucosal mast cells with dexamethasone.

Reserpine markedly elevated both the gastric secretory volume and acid output in pylorus-occlQded rats. Concurrent effective neutralisation of gastric luminal acid with oral sodium bicarbonate did not appreciably influence ulceration, mucosal mast cell degranulation o~the changes in. the superficial mucosal microvascular volume induced by reserpine in the glandular stomach

of these animals.

Reserpine provoked comparable increases in the

iii

mucosal microcirculatory blood volume in the stomachs

of rats killed either 2 or 4 h following reserpine injection. Glandular ulceration and mucosal mast cell degranulation were, however, prominent only at the end

of the 4 h. Gastric mucosal blood flow was markedly elevated after reserpine, but was significantly depressed below baseline values at the end-,of 4 h. Similarly i

reserpine, but fell to basal va_l;~s_-at the end of 4 h.

Pretreatmen-t with smooth muscle-relaxing doses of papaverine dose-dependently inhibited glandular ulcer severity, gastric mucosal microcirculatory volume changes and the increased stomach emptying rate in reserpine-treated rats. These doses appeared not to affect-gastric mast cell degranulation as well as

the gastric secretory volume and acid output.

Pretreatment with mepyramine or cimetidine did not appreciably influence glandular mucosal mast cell degranulation in reserpine-treated rats. Mepyramine dose-dependently antagonised glandular ulceration, superficial mucosal microvascular changes and the

increased stomach emptying rate in reserpine-treated

rats. Cimetidine, in both acid-inhibiting and noninhibiting doses, also prevented reserpine-provoked glandular ulceration and mucosal microcirculatory volume changes in a dose-dependent manner, but did not appreciably influence alkaloid-elevated gastric motility.

Rumenal ulceration, occurring only when gastric acid accumulated in pylorus-occluded rat stomachs, was worsened by the acid-increasing effect of reserpine. These lesions were effectively antagonised by oral sodium bicarbonate or by acid~~nhibiting doses of

iv

disodiurn cromoglycate or cimetidine.

The present study permits the conclusion that unlike rumenal ulceration, which is produced by the corrosive action of gastric acid, glandular ulcers evoked by stress in rats are largely due to factors other than gastric acid. Ulcerogenic substances, principally histamine, released mainly from degranulating stomach mast cells, initiate a series of gastric musculo-vascular effects which ultimately lead to mucosal ischaemia and ulceration. Adrenal medullary catecholamines appear to lessen glandular ulceration by antagonising these musculo-vascular changes. Other possible ulcer-producing mechanisms are also discussed.

Bibliographical Information:

Advisor:

School:The University of Hong Kong

School Location:China - Hong Kong SAR

Source Type:Master's Thesis

Keywords:gastric mucosa stomach ulcers rats diseases

ISBN:

Date of Publication:01/01/1980

© 2009 OpenThesis.org. All Rights Reserved.