Effect of antihypertensive drugs on ethanol induced gastric lesions: is there a correlation with mucosal blood flow?

We studied the effect of five antihypertensive drugs on ethanol-induced gastric haemorrhagic lesions in rats. While hydralazine aggravates these lesions, nifedipine and propranolol have a protective action. On the other hand, enalapril and prazosin have no effect. Thus the effects of antihypertensive drugs on ethanol-induced lesions do not always correlate with their reported actions on gastric mucosal blood flow.

Aggravating action of hydralazine on ethanol-induced gastric lesions.

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.

Protective effect of propranolol on ethanol-induced gastric lesions in rats: probable mechanism of action.

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.

Gastric cytoprotection.

The term 'cytoprotection' means protection against gastric mucosal injury by a mechanism other than inhibition or neutralisation of gastric acid. Several mechanisms of gastric cytoprotection have been proposed like increased mucus and bicarbonate secretion, strengthening of gastric mucosal barrier, increased gastric mucosal blood flow, decreased gastric motility, increased formation of prostaglandins and sulfhydryls, scavenging of free radicals, stimulation of cellular growth and repair, decreased release of leukotrienes etc. Some of the drugs widely used in therapy of peptic ulcer are cytoprotective e.g. sucralfate, colloidal bismuth and aluminium containing antacids. As the concept of gastric cytoprotection is becoming widely accepted, the list of drugs which have shown a cytoprotective action in animal experiments is growing rapidly. This list includes zinc sulphate, meciadanol, propranolol, dipyridamole etc.

Aggravating action of clonidine on ethanol-induced gastric lesions: probable mechanism of action.

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).

Comparison of the effects of captopril and enalapril on oxyphenbutazone and ethanol-induced gastric lesions in rats.

We have compared the effect of the converting enzyme inhibitors, captopril and enalapril, on two models of gastric ulcers, viz; ethanol and oxyphenbutazone-induced lesions in rats. Both captopril and enalapril did not affect ethanol-induced lesions. While captopril significantly protected against oxyphenbutazone-induced lesions, enalapril aggravated the lesions. This difference is probably due to the lack of the protective sulfhydryl group in the chemical structure of enalapril.

A comparison of four analgesics in post-episiotomy pain.

This study was conducted to compare the analgesic efficacy of four commonly used analgesics namely ibuprofen, analgin, paracetamol and aspirin in post-episiotomy pain. The subjects were healthy postpartum women on the obstetric service of Goa Medical College, each of whom received only one experimental medication. Subjective reports were used as indices of pain intensity or relief. Ibuprofen was found to be the most effective analgesic in post-episiotomy pain followed by analgin and paracetamol in that order. Surprisingly, aspirin was found to be no better than placebo.

Vascular desensitisation--possible role of prostaglandins.

Prolonged exposure to noradrenaline (NA) brings about an increase in the release of prostaglandin (PG)-like material from rat aortic strip. The release is greater with oxymetazoline while methoxamine decreases it. These effects are blocked by yohimbine and prazosin respectively. Pretreatment with 6-OHDA or reserpine diminishes the release of PG-like material. Barium chloride, a non-specific spasmogen, does not affect the release significantly. It appears therefore that the source of PG-like material is presynaptic and that its release mechanism is linked to an alpha 2 (alpha 2) adrenoceptor. It is proposed that this release of PG-like material contributes to the development of desensitisation in vascular tissue.

Dual action of zinc on ileal smooth muscle--zinc-calcium interaction.

Effect of zinc sulphate was studied on histamine-induced contractions on guinea-pig ileum. In doses of 1.72 X 10(-7)M or less no effects were observed. Zinc sulphate in doses of 3.44 X 10(-7)M, 6.88 X 10(-7)M and 1.72 X 10(-6)M produced dual effect. Short exposure of tissue for 10 min to zinc sulphate resulted in significant dose dependent potentiation of histamine effect whereas after washing the tissue of zinc sulphate, histamine response was inhibited significantly and in a dose dependent manner. Higher concentrations of zinc sulphate of 3.44 X 10(-6)M and above produced irreversible inhibition of histamine response. The above observations have been explained in terms of zinc-calcium interaction. It is hypothesized that interaction of zinc with calcium may take place extracellularly at membrane level and intracellularly.