To find out a convenient and reliable method of. detecting low renin status, we employed intravenous furosemide injection as a stimulatory maneuver. The results thus obtained were compared with those from the postural stimuli and basal plasma renin activity (PRA) in relation to sodium excretion. Intravenous furosemide test was performed in 66 control subjects and 44 patients with essential hypertension. The results were as follow; 1) Mean PRA in control subjects rose from $2.5{\pm}1.95$ ng/ml/hr (basal) to $4.5{\pm}2.51,\;5.2{\pm}2.49\;and\;4.2{\pm}2.44$ ng/ml/hr at 1, 2 and 3hrs after IV injection. One-hour response is more convenient in clinical practice. 2) Postural stimuli by assuming an upright posture for 3 hrs gave rise to considerable increase in PRA ($4.0{\pm}2.92\;from\;2.4{\pm}1.85$), but we found it less convenient than stimulation with furosemide. 3) The increase in PRA was much less marked in patients with essential hypertension as a whole ($2.9{\pm}2.75$). Hyporesponsiveness to furosemide stimuli was found in 34.1%. Of these hypo responders, a third had a normal basal PRA, indicating the need for this kind stimulatory procedure. 4) Younger age group showed greater renin responsiveness than older age group after furosemide stimuli. Likewise mean age of low renin patients ($52.9{\pm}5.38$ years old) was significantly higher than that of high and normal renin patients ($44.1{\pm}13.78$ years old).
The present study was designed to examine whether water extract of Acanthopanacis cortex(AC) has an effect on renal functional parameters in association with the expression of aquaporin 2 (AQP-2) and heme oxygenase-1 (HO-1) in the ischemia/reperfusion induced acute renal failure (ARF) rats. Polyuria caused by down-regulation of renal AQP 2 in the ischemia-induced ARF rats was markedly restored by administration of AC (200 mg/kg, p.o.) with restoring expression of AQP 2 in the kidney. Administration of AC lowered the renal expression of HO-1, which was upregulated in rats with ischemia/reperfusion-induced ARF. The renal functional parameters including creatinine clearance, urinary sodium excretion, urinary osmolality, and solute-free reabsorption were also markedly restored in ischemia-ARF rats by administration of AC. Histological study also showed that renal damages in the ARF rats were abrogated by administration of AC. Taken together, the present data indicate that AC ameliorates renal defects in rats with ischemia/reperfusion-induced ARF.
A high-performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of theophylline(TP) and its metabolites, 1-methyluric acid (1-MU) and 1,3-dimethyluric acid (1,3-DMU), in rat plasma and urine. An $100\;{\mu}l$ aliquot of a plasma or urine sample was mixed with $250\;{\mu}l$ of acetonitrite and vortexed. After centrifugation, $200\;{\mu}l$ (plasma) or $20\;{\mu}l$ (urine) aliquot of the supernatant was dried by $N_2$ stream and redissolved in $100\;{\mu}l$ (plasma) or $200\;{\mu}l$ (urine) of the mobile phase. A $20\;{\mu}l$ of the mobile phase solution was injected onto a $C_{18}$ reversed-phase column. The column was maintained at $45^{\circ}C$ by the aid of electric heating jacket. The mobile phase was a 3%(v/v) methanol solution in deionized water which contains sodium acetate (100 mM) and tetrabutyl ammonium hydroxide (4 mM). pH of the mobile phase was adjusted 4.5 by the addition of acetic acid. Detection limits for TP, 1-MU, and 1,3-DMU in plasma were 0.2, 0.1 and $0.1\;{\mu}/ml$, respectively and the corresponding values in urine were all $5\;{\mu}g/ml$. Inter- and intra-day variability of the assay for all compounds in the plasma samples was less than 5.5 and 3.8%, respectively. The retention times for 1-MU, 1,3-DMU, and TP were approximately 7, 8.5 and 18 min, respectively. Sample preparation procedure used in this method was simple, rapid and reproducible. Renal clearance of TP and its metabolites in rats showed plasma concentration dependency indicating renal tubular secretion and reabsorption of them.
Diltiazem inhibits calcium channels and Iεads to vascular smooth muscle rεlaxation and negative inotropic and chronotropic effects in the hεart. Diltiazem is almost completely absorbεd after oral administration, but its extent of absolute oral bioavailability is reduced because of considerable first-pass hepatic metabolism. Diltiazem is able to dilate renal vasculature and can increase the glomerular filtration rate and renal sodium excretion. The purpose of this study was to report the pharmacokinetic changes of diltiazem after oral administration of diltiazem, 20 mg/kg, in rabbits coadministered with cimetidine, 20 mg/kg and pretreated twice per day for 3 days at cimetidine dose of 20 mg/kg. The area under the plasma concentration-time curve (AUC) of diltiazem was significantly higher in rabbits pretreated with cimetidine than that in control rabbits (p<0.01), showing about 149% increased relative bioavailability. The peak plasma concentration $(C_{max})$ and elimination half-life of diltiazem were increased significantly (p<0.05) in rabbits pretreated with cimetidine compared with those in control rabbits. This findings could be due to significant reduction of elimination rate constant by pretreated with cimetidine. The effects of cimetidine on the pharmacokinetics of oral diltiazem were more considerable in rabbits pretreated with cimetidine compared with those in control rabbits. The results suggest that the dosage of diltiazem should be adjusted when the drug would be co-administerεd chronically with cimetidine in a clinical situation.
It has been known that dietary phytate decreases the absorption of body zinc pool which is composed of the dietary and endogenous zinc in the body. The purpose of this study was to examine the effect of phytate on the absorption of total bodyzinc in Zn-depleted rats. Rats were Zn-depleted with either low(0.8%) or high(1.6%) Ca diet containing sodium phytate for 4 weeks. After zinc depletion, rats were assigned into phytate or non-phytate dietary groups within each low-or high-Ca dietary group. ant feces were collected for 2 weeks of the initial collection and 1 week after dietary crossover, during which the phytate and the non-phytate diet was switched over within the same Ca group. The content of Zn and Ca measured by atomic absorption spectrophotometer and phytate content was analyzed. food intake was higher in the high Ca group than in the low Ca group(p <0.0001), and was also higher in the non-phytate group than in the phytate group(p <0.0001). Food intake and phytate level affected body weight gain in rats(p <0.0001). Zinc excretion in the total feces was higher in the phytate group than in the non-phytate group at both low and high Ca level(p <0.0001), except during the crossover collection period in high Ca group. Calcium, however, didn't show any synergistic effect on phytate effect(p <0.05). This study showed that phytate decreased the absorption of total body zinc at both low and high Ca levels in Zn-depleted rats. A large portion of total body zinc originated from the endogenous zinc pool in these rats. The results of the present study showed the same effect of phytate on the endogenous zinc in Zn-depleted rats as in a previous study, confirming that phytate adversely affects zinc bioavailability, especially under marginal and poor zinc nutrition.
Objective: Combination of two stressors on alteration of mineral footprints in animals needs due attention to meet maximum production and welfare, particularly in grazing sheep. This study tested whether ewes (Ovis aries) exposed to water deprivation and thermal-humidity stressors had altered mineral footprints in their wool, serum, urine, and feces. Methods: Nine ewes (age = 3 years; mean body weight = 41±3.5 kg) were divided among a control group with free access to water, and treatment groups with water deprivation lasting either 2 h (2hWD) or 3 h (3hWD) after feeding. Using a 3×3 Latin square design, animals were assigned to treatment groups for three sampling periods of 21 days each (n = 9). Blood was collected by jugular venipuncture. Wool was collected at the end of periods 2 and 3. Metabolic crates designed with metal grated floors were used for urine and feces collection. We measured sodium (Na), magnesium (Mg), phosphorus (P), chloride (Cl), calcium (Ca), manganese (Mn), copper (Cu), iron (Fe), and zinc (Zn). Results: The wool mineral levels did not differ between the treatment groups, although K was marginally lower (p = 0.10) in the 2hWD group. The serum and urine mineral levels did not differ between the treatments (p>0.05). Fecal K was significantly lower in the 2hWD group than in the other groups (p≤0.05). Conclusion: In conclusion, water deprivation and thermal-humidity exposure altered the excretion of K, but not of other minerals, in the wool, urine, feces, or serum of ewes. Thus, no additional mineral supplementation is needed for water deprived ewes during thermalhumidity exposure.
An experiment was carried out to study the effect of monensin administration on mammary functions in crossbred Holstein cattle. Fourteen non-pregnant late lactating crossbred Holstein cattle, approximately 270 days postpartum, were selected for the experiment. They were divided into two groups of 7 animals each. Seven animals in the treated group were given sodium monensin orally in a slow-release capsule. Animals in both control and treated groups were fed the similar diet to maintain milk production and body score at 2.5. Rice straw was fed as a source of dietary fiber throughout the experimental period. After monensin administration, a significant increase in the molar percent of ruminal propionate (p<0.05) and a significant decrease in the molar percent of ruminal acetate (p<0.05) were apparent in comparison to the pretreated period. The ratio of acetate to propionate concentration decreased significantly after monensin administration (p<0.05), while it was maintained at the similar level throughout the period of experiment in the control group. Monensin did not affect the molar percent of ruminal butyrate and valerate. The concentration of milk allantoin between the control group and monensin treated group was not different. An excretion rate of allantoin in milk decreased in animals treated with monensin (p<0.05). Mammary blood flow did not show significant difference between control and monensin treated groups. The plasma glucose concentration, arteriovenous concentration difference and mammary gland uptake of glucose remained constant in both groups. Milk yield of the later stage of lactation in the control group declined during lactation advance while a tendency to increase in the milk yield was apparent after 21 days monensin administration. Milk compositions for concentration of lactose, fat and protein in both control group and monensin treated group did not change throughout the experimental periods. From these results, it can be concluded that the action of monensin could affect the ruminal fermentation pattern. Monensin could not increase milk yield in the late lactating period.
The effect of ethacrynic acid (EA) on the renal secretion of PAH was examined in cat kidney. $C_{PAH}$ and $T_{PAH}$ were measured before and after infusion of EA $(0.5{\sim}50mg/kg)$ through the femoral vein. The following results were obtained: 1) In the dosage range of 0.5 to 25 mg/kg, EA increased the urine flow, and sodium and potassium excretion in dose-dependent manner, but the glomelular filtration rate was decreased as the dosage of EA was increased. 2) $C_{PAH}$ and $T_{PAH}$ were decreased by EA in the dosage range of 3 to 25 mg/kg and 1 to 50 mg/kg, respectively, in dose·dependent manner with the dosage to cause 50% inhibition of about 5 mg/kg. 3) With dosage of 0.5mg/kg, EA appeared to exert a great effect on diuretic response without the influence on $T_{PAH}$. At 10min after infusion of EA, a potent diuretic effect appeared, while $T_{PAH}$ did not show a significant change. These results suggest that the action mechanism of EA on tubular secretion of PAH may be different from that on natriuresis. 4) With dosage of 5 mg/kg, EA did not inhibit the Na-K-ATPase activity in microsomal fractions from both cortex and medulla. 5) The double reciprocal plot ($l/T_{PAH}$ versus $l/P_{PAH}$) suggested that EA inhibited the P AH secretion by a competitive pattern. However, probenecid, a prototypic inhibitor of the organic acid pump, had no influence on both the inhibitory effect of $T_{PAH}$ and the natriuretic effect by EA. These results suggest that in vivo EA altered tubular secretion of P AH through interactions with receptors that are not identical with the Na-K-ATPase.
We investigated diet supplementation with shiitake mushroom fruiting bodies on biochemical and histological changes in hypercholesterolemic rats. Six-wk old female Sprague-Dawley albino rats were divided into three groups of 10 rats each. A diet containing 5% Lentinus edodes fruiting bodies given to hypercholesterolemic rats reduced plasma total cholesterol, triglyceride, low-density lipoprotein (LDL), total lipid, phospholipids, and the LDL/high-density lipoprotein ratio by 34.33, 53.21, 75.00, 34.66, 25.73, and 71.43%, respectively. Feeding mushroom also significantly reduced body weight in hypercholesterolemic rats. However, it had no detrimental effects on plasma albumin, total bilirubin, direct bilirubin, creatinine, blood urea nitrogen, uric acid, glucose, total protein, calcium, sodium, potassium, chloride, inorganic phosphate, magnesium, or enzyme profiles. Feeding mushroom increased total lipid and cholesterol excretion in feces. The plasma lipoprotein fraction, separated by agarose gel electrophoresis, indicated that L. edodes significantly reduced plasma ${\beta}$ and pre-${\beta}$-lipoprotein but increased ${\alpha}$-lipoprotein. A histological study of hepatic cells by conventional hematoxylin-eosin and oil red-O staining showed normal findings for mushroom-fed hypercholesterolemic rats. These results suggest that shiitake mushrooms could be recommended as a natural cholesterol lowering substance in the diet.
The most popular way to get the animal to be co-operative for the animal experimentation is by using some kinds of general anesthetic agents. One of the most important point to take care of is, however, whether the agent(s) to be used is hinder the experimentation itself. There have been many contradictory reports of the general anesthetic agents on the renal function. Moreover, little information on the changes of the renal function by anesthesia has been available. We have done experiments to clarify and compare the effects of anesthesia induced by several general anesthetic agents on renal function in unanesthetized rabbits. Nembutal anesthesia(30 mg/kg, iv.) caused a decrease in free-water clearance, and increase in sodium and chloride excretion without significance. Thiopental anesthesia$(20{\sim}30\;mg/kg,\;iv.)$ suppressed all renal parameters tested. Chloralose(50 mg/kg, iv.) and chloral hydrate(75 mg/kg, iv.) did not change renal functions except for glomerular filtration rate, which parameter was suppressed only for a short period just after agent administration. Urethane(1 g/kg), administered by the route of either subcutaneously or intraperitoneally, suppressed renal functions lasted for the duration of experimental anesthesia. The above data suggest that it is very important to chose an appropriate anesthetic agents for a given experiment, especially experiment involved with renal function, and to interprete the data obtained from the anesthetized animal model for the expected results.
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