Effect of certain pharmacological agents on some neuropepyides and adrenal hormones in stressed rats. an evidence for a specific role in stress ulcerogenesis

This work aimed to study the effect of certain pharmacological agents [6-hydroxydopamine [6HD], metyrapone and naloxone]] on plasma adrenal hormones [corticosterone, epinephrine, norepinephrine and dopamine], brain and mucosal somatostatin and prostaglandin E2 [PGE2] as well as mucosal beta-endorphin in rats exposed to restraint stress. The specific actions of the different drugs used in this study helped to delineate the relative contribution of the different components in the pathogenesis of stress ulceration. The sympatho-adrenal medullary activity appears to be protective and neutralize the ulcerogenic effects involving the vagal activation and opioid mechanisms. Meanwhile, the adreno-cortical activity through the glucocorticoids appear to offer a permissive role in ulcer development

Involvement of and 2 - adrenoceptors in the modulation of the hyperglycaemic action of lithium in streptozotocin-diabetic rats

Intravenous lithium [4 mEq/kg] in streptozotocin-diabetic rats, increased serum glucose level but did not affect the basal serum concentration of insulin. After intravenous glucose [0.5 g/kg], lithium-treated diabetic rats showed a rise in serum glucose without any insulin response. Lithium treatment in diabetic rats also showed a significant rise in serum corticosterone, epinephrine and norepinephrine but did not affect serum dopamine. Moreover, it decreased significantly the brain concentration of norepinephrine and dopamine without any noticeable effect on brain epinephrine. The lithium-induced effects on serum glucose levels were reversibly blocked by pretreatment of the diabetic rats with the alpha 2-adrenoceptor antagonist yohimbine whereas the alpha 2-receptor antagonist prazosin and the non-selective Beta-receptor antagonist propranolol were ineffective in blocking these effects. The low insulin concentrations measured in the diabetic rats were not affected by such pretreatment. Lithium-induced rise in serum corticosterone was also inhibited by pretreatment with yohimbine but not with prazosin or propranolol

Concentration-dependent protection by glibenclamide against reperfusion induced arrhythmias in isolated rat heart

Arrhythmia associated with reperfusion of ischemic myocardium may be a major progenitor for sudden cardiac death in man. In this study, an attempt was undertaken to investigate the protective effect of glibenclamide on reperfusion induced arrhythmias in isolates rat heart. Reperfusion induced arrhythmias [premature ventricular contractions and incidence, onset and duration of ventricular tachycardia and ventricular fibrillation], cardiodynamics [heart rate, developed tension and perfusion pressure] and some biochemical changes [potassium and total protein concentrations] in isolated rat heart were investigated. The results obtained revealed that glibenclamide is effective in protecting the heart against reperfusion-induced ventricular fibrillation partly by attenuating the wash of potassium and enhancing the membrane integrity upon reperfusion

Role of endogenous opioid in the pathophysiology of stress ulcer recognition of beta-endorphin immunoreactivity in the gastric mucosa of male albino rats

The role of endogenous opiates in the pathophysiology of gastric stress ulcers was studied. Intraperitoneal naloxone [10 mg/kg body weight]; the non selective opiate antagonist was given to pylorically ligated male albino rats either subjected to restraint stress or left freely wandering and compared with similar non-treated groups. Treatment with naloxone significantly reduced the gastric secretory volume, the free and total acid concentration and output during basal and stress conditions and reduced pepsin output in the stressed group suggesting a stimulatory role of endogenous opioids on all of these parameters. Stress decreased gastric mucosal PGE2, while naloxone had no significant effect neither in the control nor in the stressed animal groups. Accordingly, opiates do not exert their effects through alteration of PGE2: On the other hand, both stress and naloxone decreased gastric mucosal somatostatin probably through increased vagal activity as opioids may act centrally to inhibit the vagus. Finally beta endorphin immunoreactivity has been identified in the present work in the gastric mucosa and was significantly decreased with conditions known to increase vagal activity as stress and treatment with naloxone suggesting a vagal role in controlling the gastric mucosal content of the peptide

Correlation of physiological stimulants of gastric secretion to the development of different types of gastric stress ulcers in male albino rats

Restraint, cold restraint, and water immersion stress were applied to pylorically ligated male albino rats in half hourly increasing duration [0.5-3.0 h]. All models of stress tested produced gastric ulcers, the indices of which were significantly correlated with the increased duration of stress exposure, with the increased gastric mucosal histamine, with the increased serum gastrin, and with the increased total acidity and proteolytic activity of gastric juice. The significant correlation between gastric mucosal histamine and serum gastrin supports a common mediator hypothesis for the former. Increased plasma epinephrine and norepinephrine correlated with the decreased volume of gastric secretion supporting decreased mucosal blood flow as a pathophysiologic factor while hypoglyceamia could not be considered as a vagal stimulant except with cold restraint since the other models showed hyperglyceamia

Antidysrhythmic activity of some nonsteroidal anti inflammatory drugs against barium chloride and aconitine cardiac dysrhythmias in guinea pigs

In our previous work, some nonsteroidal anti-inflammatory drugs demonstrated a remarkable antidysrhythmic activity against ouabain-induced dysrhythmias in urethane-anaesthetized guinea pigs. The present study was undertaken to investigate any possible antidysrhythmic properties of these drugs against other models of experimentally-induced cardiac dysrhythmias achieved by the slow intravenous infusion of barium chloride and aconitine in guina pigs. Two methods have been used for this purpose. In the first method, the drugs were tested for their ability to revert an established barium chloride and aconditine-induced cardiac dysrhythmias. In the second, the tested drugs wee given in advance to visualize if they can protect the animal from the effect of a subsequent dose of the respective dysrhythmogenic agent. Ventricular dysrhythmia induced by barium chloride was reversed by an equivalent dose [20 g/Kg] of Tiaprofenic acid, Pirprofen, Indomethacin and Asprin. On the other hand, the tested drugs, in he same dose level, were unable to revert ventricular dysrhythmias induced by aconitine. Tiaprofenic acid, Indomethacin and Aspirin, in a dose level of 20 mg/Kg, were found to produce a significant protection against dysrhythmias induced by barium chloride and aconitine. Pirprofen, in a dose level of 20 mg/Kg, was unable to protect against bariumn chloride-induced dysrhythmnias whereas, in the same dose lvel, it roduced significant protectioin against ventricular dysrhhythmias induced by aconitine. No correlation was found toexist between the antidysrhythmic effectiveness of these drugs and their effect on the serum and cardiac tissue electrolytes [N2+, K+ and Ca2+]. The relevance of these findings was discussed

Effects of verapamil, diltiazem, propanolol and quinidine on RO 13-6438-induced cardiac dysrhythmia in guinea pigs

The effect of Verapamil, Diltiazem, Propranolol and Quinidine on Ro 13-6438-induced cardiac dysrhythmia in urethane-anaesthetized guinea pigs was studied. During this study, the tested drugs were given in advance to visualize if they can protect the animal from a subsequent dose of Ro 13-6438. Intravenous injection of Ro 13-6438 in a dose level of 50 mg/kg was able to produce persistent period of ventricular tachycardia ended with the development of ventricular fibrillation. Verapamil, Diltiazem, in a dose level of 5 mg/kg and Propranolol, in a dose level of 2.5 mg/kg, were found to protect animals against dysrhythmia induced by Ro 13-6438, whereas Quinidine, in a dose level of 5 mg/kg, was found to be ineffective. A possible role of electrolytes in the genesis of Ro 13-6438-induced cardiac dysrhythmia was discussed