ABSTRACT
Endogenous nitric oxide has been proposed as one of the mediators of gastric cytoprotection. We studied the effect of the vasodilator hydralazine which acts via nitric oxide and thus is expected to have a gastroprotective action. However, hydralazine aggravates ethanol-induced gastric lesions. This effect is not influenced by pretreatment with the selective alpha 1 adrenergic antagonist prazosin but is abolished by the angiotensin converting enzyme inhibitor, captopril suggesting the involvement of the renin-angiotensin system.
Subject(s)
Animals , Captopril/pharmacology , Drug Interactions , Ethanol/toxicity , Gastrointestinal Hemorrhage/chemically induced , Hydralazine/administration & dosage , Male , Prazosin/pharmacology , Rats , Rats, Inbred Strains , Stomach/drug effects , Stomach Diseases/chemically inducedABSTRACT
The non-selective beta-adrenoceptor antagonist, propranolol, has been reported to protect against gastric injury in mice, an effect only partly due to prostaglandin release. This study was designed to confirm the gastric cytoprotective effect of propranolol in another species of animal, the rat, and investigate further its mechanism of action. Our results show that propranolol prevents both ethanol-induced gastric lesions as well as ethanol-induced contraction of the circular muscle of rat fundic strip. The local anaesthetic, lignocaine also inhibited the effect of ethanol on circular muscle. However, timolol, another non-selective beta-adrenoceptor antagonist, failed to produce such an action. The effect of propranolol was abolished by the cyclooxygenase inhibitor, indomethacin and a high dose of the guanylate cyclase inhibitor, methylene blue. The results suggest that in addition to prostaglandins, endogenous nitric oxide and the membrane stabilising action of propranolol may also be involved in its gastroprotective action.
Subject(s)
Animals , Drug Interactions , Ethanol/antagonists & inhibitors , Gastric Fundus/drug effects , Gastrointestinal Hemorrhage/chemically induced , Indomethacin/pharmacology , Lidocaine/pharmacology , Male , Methylene Blue/pharmacology , Muscle Contraction/drug effects , Propranolol/therapeutic use , Rats , Rats, Inbred Strains , Stomach Diseases/chemically inducedABSTRACT
Large doses of the imidazoline alpha 2 adrenoreceptor agonist clonidine aggravate ethanol-induced gastric lesions. The alpha 2 adrenoceptor antagonist phentolamine, the opioid antagonist naloxone and the H2 antagonist cimetidine do not prevent this action of clonidine suggesting that it is not mediated by alpha 2, opioid or H2 receptors. Further, like clonidine, high doses of phentolamine and cimetidine aggravate gastric lesions per se, suggesting that all three may be acting at a common 'receptor' site, possibly the imidazoline-preferring receptor (IPR).