It is known that BK does play a role in the cardioprotective effect of angiotensin converting enzyme (ACE) inhibitors. The present study therefore was conducted to examine the effects of bradykinin (BK) and its antagonist on survival time in spontaneously hypertensive rats (SHR) with coronary artery ligation for 15 min and continuously. We also evaluated the heart rate and blood pressure (BP) in the presence and absence of BK and BK2 receptor antagonist, D-Arg-[Hyp-D-Phe7]BK. Coronary artery was ligated in anaesthetized rats and they were artificially ventilated with room air (stroke volume, 4 ml; 48 strokes/min) as described by the previous investigators. Lead II elecrocardiogram (ECG) was recorded from subcutaneous steel needle electrodes. Results of this investigation indicated that BK treatment 4 microg/kg (i.v.) and 8 microg/kg (i.v.) caused significant (P < 0.05) increase in survival time in SHR with coronary artery ligation for 15 min and continuously as compare to their respective saline-treated controls. However, BK antagonist treatment 4 microg/kg (i.v.) abolished the increase in survival time caused by BK treatment. The mean values of survival time between the saline-treated and BK antagonist plus BK-treated rats did not differ significantly (P > 0.05). The heart rate and BP responses were greatly reduced (P < 0.001) in the presence of coronary artery ligation. These findings suggest that BK might have cardioprotective effect to increase the survival time in rats by activating BK2 receptors after coronary artery ligation.
Deficiency of surfactant in alveoli leads to increased resistance to breathing. Histamine is a mediator in allergic respiratory diseases. Though the bronchoconstrictor effect of histamine is well recognised, histamine may have additional actions that contribute to pathogenesis in these diseases. The present study aimed to observe the effect of histamine on lecithin, a major component of alveolar surfactant. Lecithin content in broncho-alveolar lavage (BAL) fluid of healthy adult male rats was estimated by enzymatic method using Boehringer-Mannheim kits. Lecithin content in these control animals was compared with that in three groups of healthy adult male rats following subcutaneous administration of 0.06 mg of histamine diphosphate at 10 minutes, 30 minutes and 60 minutes intervals, respectively. A significant reduction in lecithin levels in BAL fluid was observed up to one hour after administration of histamine. The results indicate a possible additional action of histamine in the pathogenesis of allergic respiratory diseases.
Dexamethasone blocks aromatase and phospholipase A2 enzyme activities that are essentially involved in the formation of oestrogens and prostaglandins, the key chemicals to initiate parturition. The present study was undertaken to determine whether dexamethasone, a potent glucocorticoid, could prolong gestation and/or delay parturition in rats. Dexamethasone at 0.5 mg/rat/day from Day 19 through Day 21 of pregnancy consistently prolonged gestation. Only 36% of the pregnant rats had labour with an extended parturition time. Foetal mortality rate was also high. The remaining 64% pregnant rats that did not deliver showed intrauterine foetal death and resorption. Concomitant injection of oestradiol cyclopentylpropionate or prostaglandin F2 alpha on Day 19 effectively reversed the deleterious effects of dexamethasone. 100% of the pregnant rats had successful labour at term. The parturition time and foetal mortality rate were not different from controls. The results, therefore, indicate that an excess glucocorticoid that initiates parturition in sheep conversely prolongs gestation and delays parturition in rats.
This study examined the effect of eugenol and ginger oil on severe chronic adjuvant arthritis in rats. Severe arthritis was induced in the right knee and right paw of male Sprague-Dawley rats by injecting 0.05 ml of a fine suspension of dead Mycobacterium tuberculosis bacilli in liquid paraffin (5 mg/ml). Eugenol (33 mg/kg) and ginger oil (33 mg/kg), given orally for 26 days, caused a significant suppression of both paw and joint swelling. These findings suggest that eugenol and ginger oil have potent antiinflammatory and/or antirheumatic properties.
In vivo studies involved monitoring the effect of morphine administration on catecholamine biosynthesis by the brain while in vitro studies involved studying the effect of morphine on the uptake of tritiated tyrosine by synaptosomes and its subsequent incorporation into the catecholamines. The extremely low levels of these endogenous compounds required the use of High Performance Liquid Chromatography with electrochemical detection. Intra-peritoneal injection of morphine at a dosage of 10 mg/kg did not produce appreciable changes in the catecholamine levels but a dosage of 30 mg/kg morphine was found to elevate dihydroxy phenylacetic acid content. At a dosage of 60 mg/kg, dopamine levels were elevated while noradrenaline was depleted. Morphine, at a concentration of 1 x 10(-5)M increases the incorporation of tritiated tyrosine into dopamine and dihydroxy phenylacetic acid in synaptosomal preparations.
The aim of this study was to investigate if colloidal bismuth subcitrate (CBS) can penetrate the gastric mucus barrier to reach the different sites of the antral mucosa and to estimate the time course for CBS to reach and remain in the mucosa. A single dose of CBS was administered orally to rats that were sacrificed at different time intervals post treatment. The control group received gum acacia without CBS. Colloidal bismuth subcitrate, visualised as electron dense precipitate (EDP), was seen in the gastric mucus layer, intercellular spaces and intracellularly after 30 minutes and disappeared after 6 hours. Scant amounts of EDP were observed in the gastric crypts, confined only to the upper parts of these structures. We concluded that CBS can penetrate the mucus and has a wide but uneven distribution in the gastric mucosa. Colloidal bismuth subcitrate, in the concentration given only penetrated the upper two-thirds of gastric pits and not the lower one-third. We also concluded that CBS has to be given 6 hourly to ensure its continuous presence in the gastric mucosa.
Daily intramuscular injection with thyroxine (T4) at a dose of 2.5 micrograms/100 g body weight decreased the larvae and adult worm burden of Parastrongylus malaysiensis in the brain and pulmonary arteries of male Sprague-Dawley albino rats. In contrast, rats treated with propyl thiouracil (PTU), an antithyroid drug, at a dose of 3.75 mg/100 g body weight retained greater numbers of larvae and adult worms. The results may reflect the contrasting immunomodulatory effects of T4 and PTU that influence the susceptibility of the host.
Measurement of rates of propulsion in the small intestine in control and experimental groups of male Sprague-Dawley rats (200-250 g) were carried out as a means of assessing antidiarrhoeal activity of aqueous extracts of the leaf of Psidium guajava (L.), using morphine as the standard drug of reference. Hyperpropulsion (diarrhoea) was induced by gavaging rats in a control group with Microlax, using phenol red mixed into it as a marker in the intestine, and the mean rate of the hyperpropulsion was determined. The normal rate of propulsion, defined as the percentage of the length of the ileum traversed by the front of the dye in 1 h after gavaging animals with a liquid paraffin-phenol red meal, was also determined in another control group. In experimental groups pretreated with enteral administration of either morphine or aqueous extracts, 1 h before the challenge with Microlax, the percentage inhibition to the hyperpropulsive rate (antidiarrhoeal activity) was calculated. Both morphine and the extracts produced a dose-response relationship in their antidiarrhoeal effects. A dose of 0.2 ml/kg fresh leaf extract produced 65% inhibition of propulsion. This dose is equiactive with 0.2 mg/kg of morphine sulphate. The antidiarrhoeal action of the extract may be due, in part, to the inhibition of the increased watery secretions that occur commonly in all acute diarrhoeal diseases and cholera.
Healthy adult male albino rats were subjected to inhalation of increasing doses of detergent (dioctyl sodium sulfo-succinate) aerosol ranging from 100 mg to 500 mg. Administration of 500 mg of detergent aerosol resulted in peribronchial and focal alveolar oedema in 3 out of 5 animals. The lungs of control animals which were subjected to inhalation of vehicle aerosol (ethanol and saline) did not show any abnormality. It is possible that pulmonary oedema observed in detergent aerosol inhalation may be due to the action of detergents on the surfactant system of the lung.
A comparative effect of propranolol and nifedipine administered individually and in combination at graded dose levels; and that of phenytoin at 30 mg kg-1 on maximal electroshock (MES)-induced seizure in mice was investigated. Propranolol in doses of 10 mg kg-1 and 20 mg kg-1, and nifedipine in doses of 8 mg kg-1 and 16 mg kg-1 significantly modified MES activity. Propranolol (40 mg kg-1), and a combination of propranolol (20 mg kg-1) and nifedipine (8 mg kg-1), produced antiMES activity, which was comparable to that of phenytoin (30 mg kg-1). In mice treated with propranolol and nifedipine combination, the tonic flexor and tonic extensor phase ratios (F/E ratio) were significantly higher than individual drug responses. Our findings suggest that a combination of propranolol and nifedipine has either synergistic or an additive effect in controlling MES-induced seizures in mice.
Male Sprague Dawley rats were fed semipurified diets containing 20% fat for 15 weeks. The dietary fats were corn oil, soybean oil, palm oil, palm olein and palm stearin. No differences in the body and organ weights of rats fed the various diets were evident. Plasma cholesterol levels of rats fed soybean oil were significantly lower than those of rats fed corn oil, palm oil, palm olein or palm stearin. Significant differences between the plasma cholesterol content of rats fed corn oil and rats fed the three palm oils were not evident. HDL cholesterol was raised in rats fed the three palm oil diets compared to the rats fed either corn oil or soybean oil. The cholesterol-phospholipid molar ratio of rat platelets was not influenced by the dietary fat type. The formation of 6-keto-PGF1 alpha was significantly enhanced in palm oil-fed rats compared to all other dietary treatments. Fatty acid compositional changes in the plasma cholesterol esters and plasma triglycerides were diet regulated with significant differences between rats fed the polyunsaturated corn and soybean oil compared to the three palm oils.
Surgical reduction of luteal tissue to about 20% of its total mass on day 5 pc was found to maintain gestation till term. A high degree of fetal loss was, however, evident. An identical surgical manipulation at the end of maximal luteal maturity, that is, on day 16 pc, resulted in normal maintenance of gestation. Fetal growth and their survival rate were found to be comparable to controls. An exclusive surgical extirpation of corpora lutea, on the other hand, either on day 16, 17, 18 or 19 was found to cause 100% fetal loss by day 23. However, progesterone replacement therapy concurrently with surgical luteal ablation till day 20, or surgical extirpation of the entire luteal mass when shifted on day 20, led the pregnancy to term. Present experimental findings, therefore, suggest that only about 20% of the functionally matured luteal mass until day 20 is essentially enough to maintain an ideal pregnancy status till term.
Haemorrhagic fever with renal syndrome (HFRS) is caused by a group of RNA viruses within the family of Bunyaviridae known as hantaviruses. The classical, severe form of HFRS is characterized by fever, headache, abdominal and lumbar pain, proteinuria, haemorrhagic phenomena, shock and renal failure. The disease is associated with the prototype Hantaan virus and occurs in rural areas of Korea and China with Apodemus mice as reservoir hosts. A clinically less severe form of HFRS, which is caused by Seoul virus, occurs in urban areas with the house rat Rattus novegicus as the main reservoir host. The disease in nonendemic areas may be atypical and patients with symptoms the hepatitis and minimal renal involvement have been observed in Malaysia. Outbreaks of HFRS in humans involving infected laboratory rat colonies have occurred in several medical centres in various countries. Hantaviruses cause a chronic, asymptomatic infection in rodents which excrete the virus in their lungs, saliva and urine. Man becomes infected mainly by inhalation of infected droplets from healthy rodent carriers. Seroepidemiological studies using mainly the indirect immunoflourescent antibody test of sera from humans and rats showed that hantaviruses have a worldwide distribution.
Male albino rats were chronically loaded with sodium by giving 1% NaCl solution as the sole source of drinking water. Daily fluid intake, daily urinary output and daily Na+ and K+ excretion rates were compared with control rats receiving tap water for six weeks. At the end ofsix weeks, sodium loaded animals were found to have raised plasma Na+ concentration, lowered plasma K+ concentration and lowered haematocrit value. Sodium loaded rats were also significantly more responsive to the pressor effect of submaximal doses of adrenaline, noradrenaline and angiotensin II given intravenously. It is concluded that the increase in sensitivity to adrenaline and noradrenaline may be due to changes in EGF and alterations of plasma electrolytes concentration. For angiotensin II, additionally, it may be due to low circulating endogenous angiotensin II, consequent of reduction in renin release attributed to chronic sodium loading.
The dorsal skin of 18 healthy Sprague-Dawley rats was used to investigate the reaction of connective tissue to buffered and unbuffered glutaraldehyde. Both the agents produced well-circumscribed lesions that underwent resolution within 30 days. Observation also shows that 2.0% buffered and unbuffered glutaraldehyde maintained a relatively inflammation-free status in connective tissue.
The effect of specific alpha[ or alpha2 adrenoceptor agents on the response of rat superior mesenteric-portal vein to field stimulation was investigated. In. a dose related manner, phenylephrine (alpha[ agonist) and yohimbine (alpha2 antagonists) increased while prazosin (alpha[ antagonist) and clonidine (alpha2 agonist) decreased the response of the vein to field stimulation. These effects are the same as those seen with these agents on rat and mouse vas deferens. It is suggested that, as in vas deferens, alpha1 postsynaptic and alpha2 presynaptic receptors exist in rat superior mesenteric-portal vein and that these receptors may be sufficiently sensitive in vein for their existence to be of significance in the action of these agents at clinical doses.
1. Steroid hormones have been shown to regulate the concentration of adrenergic and muscarinic receptors in many tissues. 2. The cyclic adenosine 3',5'-monophosphate (cAMP) content in rat lung tissues in response to either dexamethasone, corticosterone, deoxycorticosterone or progesterone for 7 days were measured following intraperitoneal injection of isoprenaline just before sacrificed. 3. There was a significant increase in cAMP level (P less than 0.001) in dexamethasone and corticosterone-treated rats compared to controls that received isoprenaline alone. 4. Pretreatment with deoxycorticosterone and progesterone suppressed the increase in cAMP in response to isoprenaline. 5. The effect of glucocorticoids in causing bronchodilatation in asthmatic patients is partly due to the restoration of adenyl cyclase responsiveness to beta-agonist.