Effect of spironolactone on the renin-aldosterone system in rats

PRA, PRC and the plasma concentration of aldosterone (Aldo) were measured in rats (Sp-rats) receiving a daily sc injection of Spironolactone, (Sp, 20 mg in olive oil) and in control rats (C-rats) receiving olive oil only. Animals were studied one day after starting treatment, 5 days on treatment or after 5 weeks on the study. PRA, PRC and Aldo were significantly increased in Sp-rats as compared to C-rats throughout all the study. In additional Sp-rats and C-rats, the urine volume, serum Na+ and K+ concentration, Na+ and K+ intake and the urinary excretion of Na+, K+ and aldosterone-18-glucuronide (UAldV) were serially measured during 5 weeks. The total radioactivity plasma clearance after an i.v. bolus injection of 3H-aldosterone was subsequently measured in (5 Sp-rats and 5 C-rats). No significant differences in serum Na+ and K+ concentration and in Na+ and K+ balance were observed between Sp-rats and C-rats. UAldV was significantly higher in Sp-rats than in C-rats during all the study. After 5 weeks on treatment the total radioactivity plasma clearance was significantly higher in Sp-rats than in C-rats. These results indicate that Sp, at high dosage, stimulates renin release and aldosterone secretion by a mechanism unrelated to alterations in Na+ and K+ balance.     

他克莫司对大鼠血糖的影响及其作用机制

目的 观察不同浓度的他克莫司对大鼠血糖的影响.方法 选取雄性SD大鼠30只,体重70～85g,随机等分为三组.A组大鼠为他克莫司加五脂胶囊组,每日给予他克莫司(普乐可复Astellas Ireland Co.,Ltd生产)2 mg/kg和五酯软胶囊(四川光大制药有限公司生产)0.2粒/kg;B组为他克莫司组,每日给予他克莫司2 mg/kg;C组为对照组,每日给予同等量生理盐水,三组大鼠均在空腹时灌胃给药,用药1h后喂食.用药时间为5个月.每月监测大鼠他克莫司血药浓度和空腹血糖.结果 在用药的1～5个月期间,A组大鼠他克莫司血药浓度均明显高于B组.在用药的第1个月和第2个月,三组大鼠空腹血糖无明显差异(P＞0.05),用药第3个月后,A、B两组大鼠血糖均明显高于对照组(P＜0.01),A组大鼠血糖略高于B组,二者之间差异并无统计学意义(P＞0.05);用药第4、5个月后A、B两组大鼠的血糖持续升高,并且A组大鼠血糖明显高于B组(P＜0.01);A组的胰岛素分泌指数和敏感指数均明显低于C组(P＜0.01).结论 他克莫司通过减少胰岛素的分泌、增加胰岛素抵抗导致大鼠血糖升高,这种升血糖作用呈时间依赖性和浓度依赖性.     

Effect of plasmin on the efferent sympathetic activity in rats and rabbits

The change of efferent sympathetic activity at intravenous administration of plasmin and perfusion of the isolated carotid sinus hes been studied in experiments on rabbits and rats. The correlation between changes of biochemical blood parameters and changes of its activity has been noted. The maximum hypercoagulative effect conforms to maximum increase of sympathetic activity as at intravenous administration so at perfusion. An increase of the efferent sympathetic activity is much higher in case of intravenous plasmin administration than in perfusion of the isolated carotid sinus.     

Effect of the nucleotides CMP and UMP on exhaustion in exercise rats

The aetiology of muscle fatigue has yet not been clearly established. Administration of two nucleotides, cytosine monophosphate (CMP) and uridine monophosphate (UMP), has been prescribed for the treatment of neuromuscular affections in humans. Patients treated with CMP/UMP recover from altered neurological functions and experience pain relief, thus the interest to investigate the possible effect of the drug on exhausting exercise. With such aim, we have determined, in exercised rats treated with CMP/UMP, exercise endurance, levels of lactate, glucose and glycogen, and the activity of several metabolic enzymes such as, creatine kinase (CK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST). Our results show that rats treated with CMP/UMP are able to endure longer periods of exercise (treadmill-run). Before exercise, muscle glucose level is significantly higher in treated rats, suggesting that the administration of CMP/UMP favours the entry of glucose in the muscle. Liver glycogen levels remains unaltered during exercise, suggesting that CMP/UMP may be implicated in maintaining the level of hepatic glycogen constant during exercise. Lactate dehydrogenase and aspartate aminotransferase activity is significantly lower in the liver of treated rats. These results suggest that administration of CMP/UMP enable rats to endure exercise by altering some metabolic parameters.     

Effect of glucocorticoids on the formation of methemoglobin in rats

Experiments on rats showed that treatment of rat with hydrocortisone, dexamethasone and diplacin for 14 days increases the content of methemoglobin in blood. In vitro experiments revealed that dexamethasone in a concentration of 10(-6) M increased the amount of methemoglobin in the whole blood and did not change its amount in hemolysate. The data obtained show the participation of erythrocyte membranes in methemoglobin-forming effect of the studied substances.     

Effect of N-acetylcysteine on the pharmacokinetics of acetaminophen in rats

Oral administration of N-acetylcysteine (163 mg/kg at zero time and 82 mg/kg 30 minutes later) to adult male Sprague-Dawley rats given an intravenous injection of acetaminophen, 150 mg/kg at zero time, increased the formation of acetaminophen sulfate and thereby enhanced the elimination of acetaminophen. Apparently, N-acetylcysteine is an in vivo source of inorganic sulfate since availability of the latter is rate-limiting in the formation of acetaminophen sulfate. Increased metabolic conversion of acetaminophen to its sulfate conjugate results in decreased formation of other metabolites of acetaminophen, presumably including the reactive metabolite responsible for the hepatotoxic effect of the drug. This may account, at least in part, for the protective effect of N-acetylcysteine against acetaminophen-induced hepatotoxicity.     

Effect of gallium nitrate in vitro and in normal rats

Gallium nitrate (GN) is an inhibitor of bone resorption and thereby may result in a change in coupled bone formation. In the present investigation the effects of GN on bone formation were studied in the rat osteosarcoma (ROS) 17/2.8 cell line and normal diploid rat osteoblasts (ROB) in vitro and the femur of rats treated in vivo, measuring mRNA levels for two osteoblast parameters, type I collagen, a marker of matrix formation, and osteocalcin, a bone specific protein and also histone H₄, a marker of cell proliferation. GN, at 50 μM for 3 h, increased type I collagen mRNA levels by 132% in ROS 17/2.8 cells and by 122% in proliferating ROB cells. Osteocalcin (OC) mRNA levels were decreased by 61% in ROS 17/2.8 cells and by 97% in differentiated ROB cells. These changes occurred in the absence of any effects on cell proliferation. Seventy-day-old female rats were then treated with GN, 0.5 mg/kg/day, for 3 weeks. As previously reported, GN decreased serum calcium levels, but had no effect on lumbar or femoral bone density. In contrast to the in vitro effects, GN had no effect on type I collagen steady-state mRNA levels in the femur; however, it decreased OC steady-state mRNA levels in the femur by 58%. These results suggest that GN has similar in vitro effects in transformed and normal osteoblasts, while the collagen-stimulatory effects observed in vitro cannot be extrapolated to in vivo models. The consistent inhibition of osteocalcin in vitro and in vivo suggests a more specific target for GN that may relate to its effects in inhibiting bone resorption in normal rats.     

Effect of acetylcholine on the tail artery reaction in rats

The response to acetylcholine (10(-5) g/ml) was studied on the rat tail artery perfused with Krebs buffer. Perfusion with acetylcholine produced vasodilation (by 69%) in arteries pre-constricted with transmural nerve stimulation. Atropine (10(-6) g/ml) blocked more than 95% of this response. Acetylcholine had a vasodilating effect on arteries pre-constricted with norepinephrine.     

Effect of the isoflavone genistein against galactose-induced cataracts in rats

Worldwide, ocular cataracts are a major cause of human blindness. A key goal of cataract-related research is to identify simple, cost-efficient but effective ways to prevent cataract formation or progression. Genistein is a naturally occurring dietary isoflavone with well-documented estrogenic, antioxidant, and protein tyrosine kinase inhibitor activity, which in turn modulates the activity of several enzymes involved in cell signaling and proliferation. Furthermore, many isoflavones have been shown to be potent inhibitors of aldose reductase, which is an important rate-limiting enzyme in the process of cataract induction in the metabolic disease galactosemia. In order to assess the potential for genistein to mitigate cataract formation, we have studied its effects in the animal model of dietary galactose-induced cataracts in adult male rats. Our experimental hypothesis was that dietary genistein would prevent or delay the progression of cataracts induced by high dietary intake of galactose. Our results show that the isoflavone genistein was not able to completely prevent galactose-induced cataract formation, but genistein did delay the progression of cataracts induced by dietary galactose. In addition, we found that dietary galactose decreased concentrations of serum somatostatin, while adding genistein decreased the serum glucose level but increased the serum testosterone level. As an initial inquiry into the mechanisms by which the partial protective effect of genistein could be mediated, we found that genistein increased the expression of connexin (Cx) 43 in the lens but did not affect the expression of soluble guanylyl cyclase (sGC) subunits. This finding suggests that the partial protective effect of genistein on cataract induction appears to be unrelated to sGC but may be mediated by enhanced expression of Cx43 and changed metabolic state.     

Effect of Yoshida ascites tumour on the circulation in rats

The circulation in anaesthetized rats with Yoshida ascites tumour was studied. Cardiac output was determined according to the reference flow method, while the distribution of cardiac output by labelled microspheres 15 mu in diameter. Arterial blood pressure decreased by 39 mm Hg and TPR by 23% at unaltered cardiac output. Blood flow of the brain and the coronaries increased by 39-43% while that of the kidney and the intestines decreased by 43 and 28%, respectively. The cardiac output fractions of the brain, the coronaries and the hepatic artery increased considerably, while that of the kidney decreased. The haematocrit decreased from 43 to 23%. It is assumed that part of the circulatory alterations (redistribution of cardiac output) were due to the anaemia and its consequences, while the others (arterial hypotension, lack of increase in cardiac output) should be regarded as an effect of a factor reaching the circulation from the cells of the ascites tumour.     

Effect of long-term hypergravitation on the skeletal-muscular tissue in rats

The space flight or simulated gravitational unloading lead to the muscle atrophy, slow-to-fast transformation of muscle fibers and myofibrillar damages both in humans and animals (1, 7, 13, 17). This process could be prevented by the exercise training during space flight (1), (partly) by periodic weight support during unloading (13). It has been demonstrated in these studies that there is some level of force production necessary for the maintenance of skeletal muscle properties. It is known that adaptation to the physical training frequently induces augmentation in cross-sectional area (CSA) of muscle fibers (MF), transformation of fibers, augmentation of mitochondrial volume density, and increase in absolute volume of myofibrillas. Numerous observations suggest importance of gravitational loading in regulating muscle mass. The centrifuging is believed to be useful for preventing muscle functional and structural losses under microgravity. But there are few studies designed to investigate effect of artificial gravity on the skeletal musculature (2, 7). Our objective was to investigate structural adaptation in slow-twitch soleus muscle (percentage of connective tissue and central nuclei, fiber size, myosin heavy chain isotope, myofibrillar proteins and mitochondria volume density) after 19 and 33 days of hypergravity.