Jamaican vomiting sickness. Biochemical investigation of two cases

We identified methylenecyclopropylacetic acid, a known metabolite of hypoglycin A, in the urine of two patients with Jamaican vomiting sickness. Excretion of unusual dicarboxylic acids such as 2-ethylmalonic, 2-methylsuccinic, glutaric, adipic and dicarboxylic acids with eight and 10 carbon chains were also detected in both patients. The amounts of these dicarboxylic acids were 70 to 1000 times higher than normal. These metabolites have also been identified in urine of hypoglycin-treated rats. This evidence links hypoglycin A to Jamaican vomiting sickness as its causative agent. Urinary excretion of short-chain fatty acids was also increased up to 300 times higher than normal. These results indicate that, despite their clinical and histologic similarities, the cause and biochemical mechanisms of Jamaican vomiting sickness differ distinctly from those of Reye's syndrome in which these abnormal urinary metabolites are not appreciably increased.     

Metabolism of linoleamides. I. Absorption, excretion and metabolism of N-(alpha-methylbenzyl)linoleamide in rat and man

1. In urine of rats dosed with N-(alpha-methylbenzyl)linoleamide (MBLA), three dicarboxylic acid monoamides, N-(alpha-methylbenzyl)succinic acid monoamide, N-(alpha-methylbenzyl)glutaric acid monoamide and N-(alpha-methylbenzyl)adipic acid monoamide, were identified. Conjugated alpha-methylbenzylamine, hippuric acid and conjugates of the dicarboxylic acid monoamides were also found in the urine. N-(alpha-Methylbenzyl)succinic acid monoamide was the main metabolite in rats. 2. Biliary excretion of radioactivity was studied in rats, cannulated for collection of bile and duodenal infusion, after oral administration of N-(alpha-methylbenzyl)[1-14C]linoleamide. With constant duodenal infusion of bile, about 7% of the dose was excreted in the bile, while excretion of radioactivity was negligible without bile infusion. 3. The g.l.c. analysis of human urine after oral administration of MBLA revealed that two dicarboxylic acid monoamides were present and N-(alpha-methylbenzyl)succinic acid monoamide was the main metabolite. 4. MBLA was excreted unchanged in the faeces of men who received MBLA to the extent of about 53% dose in 3 days. 5. MBLA was not detected (less than 1 mug/ml) in the serum of a volunteer who had been taking an oral daily dose of 1500 mg of MBLA for 3 months.     

Effect of bile duct ligation on bile acid metabolism in rats

The effect of bile duct ligation on the quantitative and qualitative changes of bile acids in serum, liver, urine, and feces, and the concentration of cholesterol and phospholipids in serum and liver were examined in male rats. The concentration of bile acids in serum increased over 100-fold on day 5 but was lower than the 5-day level on days 10 and 15. The concentration in the liver also increased about 10-fold. beta-Muricholic acid predominantly increased but the secondary bile acids, deoxycholic acid and hyodeoxycholic acid, decreased. The urinary excretion of bile acids increased to about 40 mg/day per rat on the first day of bile duct ligation but this increase was reduced on day 2 to about half and remained at that level until day 24. These values exceeded that of fecal bile acids, 12 mg/day per rat, before bile duct ligation. The amount of bile acid sulfates in the urine was as low as 1% of the total. The urinary non-sulfated bile acids consisted mainly of beta-muricholic acid (60%) and cholic acid (20%), while the sulfates contained a considerable amount of unidentified acidic substances (40%) in addition to cholic acid and beta-muricholic acid. The concentration of cholesterol and phospholipids in serum markedly increased on day 5 but declined gradually thereafter. The liver cholesterol concentration did not change but the phospholipid concentration decreased. Fecal sterols did not change in both the total amount and composition. These data indicated that daily synthesis of bile acids, especially beta-muricholic acid, was accelerated in bile duct-ligated rats.     

Suberylglycine excretion in the urine from a patient with dicarboxylic aciduria

Suberylglycine (HOOC(CH2)6CONHCH2COOH) was found in the urine from a patient with C6-C10-omega-dicarboxylic aciduria and unexplained episodes of lethargy and unconsciousness. The total excretion of adipic, suberic and sebacic acid ranged from 0.77 to 1.3 mg/mg creatinine after episodes of acute attack of the disease. Suberylglycine, identified by gas chromatography/mass spectrometry, was repeatedly found in the urine samples. The amount of this conjugate ranged from 0.2 to 0.5 mg/mg creatinine. The precursors of the dicarboxylic acids are suggested to be long chain monocarboxylic acids, oxidized through omega- and beta-oxidation to adipic, suberic and sebacic acid. Suberylglycine is subsequently formed by glycine-N-acylase catalyzed conjugation.     

Formic acid excretion in rats exposed to trichloroethylene: a possible explanation for renal toxicity in long-term studies

Rats exposed to trichloroethylene, either by gavage or by inhalation, excreted large amounts of formic acid in urine which was accompanied by a change in urinary pH, increased excretion of ammonia, and slight increases in the excretion of calcium. Following a single 6-h exposure to 500 ppm trichloroethylene, the excretion of formic acid was comparable to that seen after a 500 mg/kg dose of formic acid itself, yet the half-life was markedly different. Formate excretion in trichloroethylene treated rats reached a maximum on day 2 and had a half-life of 4-5 days, whereas urinary excretion was complete within 24 h following a single dose of formic acid itself. Formic acid was shown not to be a metabolite of trichloroethylene. When rats were exposed to 250 or 500 ppm trichloroethylene, 6 h/day, for 28 days, the only significant effects were increased formic acid and ammonia excretion, and a change in urinary pH. There was no evidence of morphological liver or kidney damage. Long-term exposure to formic acid is known to cause kidney damage suggesting that excretion of this acid may contribute to the kidney damage seen in the long-term studies with trichloroethylene.     

Epidermal growth factor (EGF) increases the renal amino acid transport capacity in amino acid loaded rats

In anaesthetized adult female rats, the influence of epidermal growth factor (EGF) on renal amino acid handling was investigated in glutamine, arginine (both 50 mg/100 g b.wt. per hour), or alanine (90 mg/100 g b.wt. per hour) loaded animals. Continuous infusions of the three amino acids were followed by an increase in the fractional excretion (FE) of the administered amino acids as well as of the other endogenous amino acids. Under load conditions (alanine, arginine or glutamine), EGF pretreatment (8 micrograms/100 g b.wt. subcutaneously for 8 days, twice daily 8 a.m. and 4 p.m.) was followed by a stimulation of renal amino acid reabsorption. The increase in the fractional excretion of the administered amino acids was significantly lower than in non-EGF-treated rats. These changes in amino acid transport were connected with a significant reduction of GFR after EGF pretreatment (0.96 +/- 0.10 vs. 0.62 +/- 0.07 ml/min x 100 g b.wt.) and a distinct increase in sodium excretion (2.98 +/- 0.55 vs. 4.97 +/- 0.71 muval/100 g b.wt. x 20 min). After loading with p-aminohippurate (PAH; 200 mg/100 g b.wt.), PAH excretion in EGF rats was increased by about 20%, whereas urinary protein excretion was lower in EGF pretreated rats (control: 0.45 +/- 0.04 vs. EGF: 0.18 +/- 0.03 mg/100 g b.wt. x 20 min). The PAH load reduced amino acid reabsorption as a sign of overloading of renal tubular transport capacity, but in EGF pretreated animals the amino acid excretion was only slightly increased under these conditions. Furthermore, EGF pretreatment depressed normal kidney weight gain significantly (874 +/- 18 vs. 775 +/- 32 mg/100 g b.wt.). EGF can improve the renal tubular transport capacity, but, compared to well-known stimulators of renal transport like dexamethasone or triiodothyronine, its effect is only of a moderate degree.     

Urinary excretion of amino acids in normal and cystinuric dogs

The 24-h urine excretion of 20 amino acids was investigated in 24 cystinuric and 15 normal dogs. The diagnosis of cystinuria was based on infrared spectroscopy of removed uroliths, which in all cases were composed of pure cystine. Seven of 24 cystinuric dogs showed normal cystine excretion compared to normal dogs, and four of 24 dogs showed normal total amino acid excretion. In contrast to earlier investigations, almost half of the cystinuric dogs (46%) showed elevated excretion of five or more amino acids. Isolated cystinuria, or isolated dibasic amino aciduria was not found. Compared to normal dogs, the cystinuric dogs showed a significantly (P < 0.05) increased excretion of cystine, arginine, lysine, cystathionine, glutamic acid, threonine and glutamine. There was a significant correlation (P < 0.05) between the urinary excretion of cystine and 10 other amino acids, with the highest correlation found (P < 0.001) for arginine, lysine, cystathionine, ornithine and 1-methyl-histidine. Three patterns of amino acid excretion could be identified: (1) increased excretion and a significant correlation with cystine for the three dibasic amino acids (lysine, arginine and ornithine), compatible with a common reabsorption mechanism as shown in man. This pattern was also found for cystathionine and glutamic acid, which might indicate a relation in metabolism or transport; (2) increased excretion but no correlation with cystine for glutamine, threonine and citrulline; (3) good correlation with cystine, but no increased excretion for 1-methyl-histidine, phenylalanine, 3-methyl-histidine, leucine and alanine. The great variation in urinary cystine excretion suggests that factors other than the excretion of cystine must be considered as causes of cystine urolith formation. For example, cystinuric dogs were found to have lower diuresis than normal dogs and produced urine with higher cystine concentration thereby increasing the risk of cystine urolith formation.     

Effect of ethynylestradiol on biliary excretion of bile acids, phosphatidylcolines, and cholesterol in the bile fistula rat

The effects of ethynylestradiol on endogenous bile acids, their capacity to conjugate and excrete intravenously infused cholic acid, the concentrations of biliary cholesterol and lecithin, and the individual molecular species of phosphatidylcholine have been determined in male and female Sprague-Dawley rats. Endogenous biliary bile acids were analyzed by gas-liquid chromatography-mass spectrometry. Eleven bile acids were identified and several minor bile acids, primarily muricholates, could not be completely characterized. After 5 days of treatment with ethynylestradiol (1 mg/kg per day), the percentage of cholic acid decreased and the percentage of 6beta-hydroxylated bile acids, including several monounsaturated species, increased. Ethynylestradiol caused a decrease in bile acid-independent bile flow. Intravenous infusion of cholic acid at a high concentration caused cholestasis in control animals but, after ethynylestradiol treatment, cholestasis developed during the infusion of a much lower concentration of cholate, indicating a lowered threshhold for bile acid-induced cholestasis. In the treated rats, there was a slight increase in excretion of unconjugated endogenous bile acids, and a striking impairment of conjugation of intravenously administered cholic acid. One of the few sex-related differences observed was an increased concentration of biliary phospholipids in untreated male rats. Both phospholipid and cholesterol concentrations in the bile were higher in the treated animals. The molar percentage of cholesterol was always 1-2%, but it was slightly higher in treated animals, especially males. Ethynylestradiol treatment also affected biliary phospholipid by causing a marked increase of phosphatidylcholine species containing palmitic and oleic acid residues and a decrease of species containing stearic and linoleic acid residues. There was no increase in biliary excretion of long chain polyunsaturated species, which might have indicated damage to membranes, in response to ethynylestradiol either alone or with cholic acid infusion. Some of these ethynylestradiol-induced changes in biliary bile acid and lipid excretion are probably peculiar to the rat, but others, such as the increase in molar percentage of cholesterol and cholestasis, may be relevant to disorders in man, especially cholesterol gallstones and idiopathic cholestasis of pregnancy.     

Influence of gender on renal thiazide diuretic receptor density and response

The influence of gender and gonadectomy on (1) the density of the renal thiazide-sensitive ion transporter, as quantitated by the ability of renal membranes to bind (3H)metolazone, and (2) the changes in the urinary excretion of electrolytes caused by maximal bendroflumethiazide (BFTZ) in Sprague-Dawley rats was determined. The density of the thiazide receptor was twofold higher (P < 0.001) in females than in males. Orchiectomy increased thiazide receptor significantly in one of two studies (P < 0.01). Ovariectomy decreased thiazide receptor by more than 20% (P < 0.01) in both studies. The rates of the urinary excretion of sodium and chloride after BFTZ and the increases in the urinary excretion of sodium, chloride, and ammonium caused by BFTZ were greater in intact females than in intact males; BFTZ decreased the urinary excretion of calcium 50% in intact females, but not in intact males. Regression analysis of the thiazide receptor (in intact and gonadectomized animals) versus the urinary excretion of electrolytes before and after BFTZ yielded a model in which one-third of the variation in thiazide receptor could be related to the change in the excretion of calcium and ammonium produced by BFTZ, raising the possibility that the density of the thiazide receptor might be related to calcium or acid-base homeostasis. It was concluded that the renal excretion of sodium, chloride, calcium, and ammonium are, in part, controlled by gender and sex hormones via their regulation of the renal density of the thiazide diuretic receptor.     

Evaluation of liver function by co-administration methodology using 13C-labelled benzoic acid and hippuric acid coupled with nuclear magnetic resonance spectroscopy

The amount of hippuric acid synthesized and excreted in the urine after benzoic acid loading (hippuric acid test) is a useful index of liver function. However, the hippuric acid test gives erroneous results in the event of failure of renal excretory function. A new stable isotope co-administration methodology using nuclear magnetic resonance (NMR) spectroscopy has been developed to overcome this defect. [7-(13)C]Benzoic acid and [glycine carbonyl-13C]hippuric acid ([gly-13C]hippuric acid), each 0.4-0.6 mmol kg(-1) were simultaneously administered intravenously as probes to normal or liver-injured rats and the urine was analysed by 100 MHz 13C NMR spectroscopy. Consequently, urinary excretion of [7-(13)C]hippuric acid formed from [7-(13)C]benzoic acid and [gly-13C]hippuric acid was successfully traced with very simple and convenient procedures. The urinary excretion of [7-(13)C]hippuric acid indicated the combined functions of hippuric acid synthesis and renal excretion, whereas that of [gly-13C]hippuric acid was indicative of renal excretion of hippuric acid only. The heights of resonances for C7 of [7-(13)C]hippuric acid and the glycine carbonyl carbon of [gly-13C]hippuric acid were used to calculate the concentrations of labelled hippuric acids. [7-(13)C]Hippuric acid was excreted more slowly than [gly-13C]hippuric acid by both normal and liver-injured rats. The liver-injured rats excreted the labelled hippuric acids more slowly than the normal rats. The kinetic parameters were computed for the individual rats on the basis of Michaelis-Menten elimination for benzoic acid and first-order elimination for hippuric acid. The maximum rates of metabolism (Vmax) (4.8-5.8 micromol min(-1) kg(-1)) and the renal elimination rate constants of hippuric acid (Kre) (0.010-0.021 min(-1)) in the liver-injured rats were lower than those (Vmax 6.7-11.8 micromol min(-1) kg(-1); Kre 0.026-0.045 min(-1)) in the normal rats. These results have demonstrated that liver function can be evaluated from the Vmax value even though the renal function of hippuric acid excretion (Kre) is impaired. Thus the co-administration methodology is feasible and can remove the defect of the previous hippuric acid test. These results could form the basis for a more convenient and reliable hippuric acid test in man.     

Increased urinary excretion of 3-hydroxyisovaleric acid and decreased urinary excretion of biotin are sensitive early indicators of decreased biotin status in experimental biotin deficiency

To assess the utility of various indicators of biotin status, marginal biotin deficiency was induced experimentally in normal adults. Ten subjects consumed a diet that contained enough avidin to bind seven times more biotin than that in the diet. Blood and 24-h urine samples were collected before the diet began and twice weekly thereafter for 20 d. The urinary excretion and serum concentration of biotin and its two principal inactive metabolites bisnorbiotin and biotin sulfoxide were determined after HPLC separation with an avidin-binding assay. The urinary concentration of 3-hydroxyisovaleric acid, an indicator of reduced activity of a biotin-dependent enzyme, was quantitated by gas chromatography-mass spectrometry. The urinary excretion of 3-hydroxyisovaleric acid increased significantly (P < 0.0001). For all subjects, the urinary excretion of both biotin and bisnorbiotin decreased significantly (P < 0.0001 for each). In contrast, the mean serum concentration of biotin did not decrease significantly (P = 0.06). These data provide evidence that the urinary excretion of 3-hydroxyisovaleric acid and the urinary excretion of biotin are early and sensitive indicators of biotin deficiency and that the serum concentration of biotin is not.     

The value of beta-2 transferrin analysis and MR cisternography for the diagnosis of cerebrospinal fluid fistulas

Blood chemical values, including ketone bodies, were measured in 25 cows with abomasal displacement (displacement group), 16 cows with primary ketosis (ketosis group), and nine normal controls to investigate the pathophysiology of abomasal displacement. Increases in aspartate aminotransferase, gamma-glutamyl transpeptidase, non-esterified fatty acid (NEFA), and ketone bodies (3-hydroxybutyric acid and acetoacetic acid) were observed in the displacement and ketosis groups. Total cholesterol increased significantly in the ketosis group but decreased in the displacement group. Glucose was significantly low and reversely correlated to ketone bodies in the ketosis group but was not low and was not correlated with ketone bodies in the displacement group. While NEFA was correlated to ketone bodies in the ketosis group, it was not in the displacement group. A correlation between the values of acetoacetic acid and 3-hydroxybutyric acid was seen in both the ketosis and displacement groups. The fact that blood chemical values in ketosis cows were clearly different from those in displacement cows suggest that the biochemical mechanism of ketogenesis is different between these two groups.     

Converting enzyme inhibition causes hypocitraturia independent of acidosis or hypokalemia

BACKGROUND: Angiotensin II stimulates the proximal tubular Na/H antiporter and increases proximal tubular cell pH. Because intracellular pH may affect urinary citrate excretion and enzymes responsible for renal citrate metabolism, the present studies examined the effect of enalapril, an angiotensin converting enzyme inhibitor, on the activity of renal cortical ATP citrate lyase and urinary citrate excretion. METHODS: Enalapril was given to rats (15 mg/kg/day) for seven days and to humans (10 mg twice daily) for 10 days. Blood and 24-hour urine samples were obtained in both groups. Renal cortical tissue from rats was analyzed for enzyme activity. RESULTS: In rats, enalapril decreased urinary citrate excretion by 88%. The change in urinary citrate was not associated with a difference in plasma pH, bicarbonate nor potassium concentration. However, similar to metabolic acidosis and hypokalemia, enalapril caused a 42% increase in renal cortical ATP citrate lyase activity. When given to humans, enalapril significantly decreased urinary citrate excretion and urine citrate concentration by 12% and 16%, respectively, without affecting plasma pH or electrolytes. CONCLUSIONS: Enalapril decreases urinary citrate in rats and humans. This is due, at least in part, to increases in cytosolic citrate metabolism through ATP citrate lyase in rats similar to that seen with chronic metabolic acidosis and hypokalemia. The effects of enalapril on urinary citrate and renal cortical ATP citrate lyase occur independently of acidosis or hypokalemia but may be due to intracellular acidosis that is common to all three conditions.     

柠檬酸对钨酸及磷钨酸的催化活性的改进

以磷钨酸/钨酸-柠檬酸为催化体系,在无有机溶剂和相转移剂的情况下,催化30%过氧化氢氧化环己酮合成己二酸。当磷钨酸∶柠檬酸∶环己酮∶过氧化氢=1∶20∶400∶200(0物质的量比,磷钨酸用量为0.25mmol)时,使用柠檬酸来调节钨酸催化活性,反应8h时,己二酸分离产率达81.2%、产品熔点为150￣153℃;以钨酸为催化剂,当钨酸∶柠檬酸∶环己酮∶过氧化氢=1∶2∶40∶200(物质的量比,钨酸用量为2.5mmol)时,反应8h,己二酸分离产率只有82.5%、产品熔点为150￣153℃。反应时间在2￣8h内,随反应时间的延长,己二酸分离产率增大,而8h后略有下降。     

Accurate amniotic fluid bilirubin analysis from the "bloody tap". A preliminary report

Prolonged isolation of rats resulted in hyperactivity in the open field and a significant increase in 24 hr urinary excretion of MHPG (3-methoxy-4-hydroxyphenylglycol). Exploratory activity of group-housed rats in open field was not associated with raised MHPG excretion, compared with that of rats remaining in home cages. Exposure of group-housed rats to 4 degrees C for 2 hr also increased urinary excretion of MHPG. Pretreatment of isolated rats with dl-, d-propranolol or practolol abolished hyperactivity of isolated rats and reduced MHPG output in these rats and in rats exposed to cold. dl-Propranolol did not reduce activity of group-housed rats in open field or their urinary excretion of MHPG. It is suggested that propranolol may have a selective inhibitory effect on stress-induced increases in noradrenaline turnover.     

Effect of sex hormones on oxalate-synthesizing enzymes in male and female rat livers

PURPOSE: We studied the effect of changes in sex hormones on oxalate metabolism in rats. MATERIALS AND METHODS: Adult male and female rats were administered a precursor of oxalate, and the relationship between dose and urinary oxalate was examined. Levels of sex hormones were varied in rats and glycolate oxidase (GO) and serine pyruvate aminotransferase (SPT) activities were measured under the conditions of being fed tap water or loading with 0.5% ethylene glycol. In addition, urinary oxalate excretion was evaluated. RESULTS: Ethylene glycol and glycolate increased urinary oxalate concentration in male rats dose-dependently but less in female rats. There was almost no change during glycine loading in either male or female rats. GO activity was significantly lower in intact female and gonadectomized male rats. SPT activity was slightly higher in the female than in the male controls. There were no differences in urinary oxalate excretions between male and female rats. During ethylene glycol loading, GO and SPT activities were similar to those with tap water intake. However, urinary oxalate excretion increased to two times the control value in male rats but only slightly increased in female rats. CONCLUSIONS: Sex-related differences exist in the metabolic conversion of glycolate to oxalate in rats, and GO activity is promoted by testosterone. Although difference in GO activity has no physiological effect on oxalate synthesis, GO activity affects urinary oxalate excretion during ethylene glycol loading. We could also conclude that estrogen decreases GO activity in male rats from our results.     

Urinary kallikrein: a marker of blood pressure sensitivity to salt

We evaluated if a rat strain inbred for low urinary kallikrein excretion differs from normal-kallikrein Wistar rats regarding blood pressure levels in basal conditions and during alterations in sodium balance. Blood pressure was measured in unanesthetized rats on normal sodium intake. Then, blood pressure sensitivity to salt was evaluated over a period of 20 days of high sodium diet (0.84 mmol per g chow). Low-kallikrein rats showed greater systolic blood pressure levels (125 +/- 3 vs. 114 +/- 2 mm Hg in controls, P < 0.01) at nine weeks of age. Systolic blood pressure was increased after sodium loading in the low-kallikrein group and remained unchanged in controls (150 +/- 6 vs. 112 +/- 2 mm Hg, P < 0.01). This effect was associated with a reduced cumulative urinary excretion of sodium in the low-kallikrein rats. No group difference was found in the clearance of endogenous creatinine in basal conditions. Urinary creatinine excretion decreased during sodium loading, particularly in the low-kallikrein group. The group-difference in urinary kallikrein excretion found in basal conditions (6.85 +/- 0.31 vs. 20.74 +/- 1.71 nkat/24 hr in controls, P < 0.01) was enhanced by high salt diet (2.96 +/- 0.67 vs. 22.07 +/- 2.47 nkat/24 hr in controls, P < 0.01). In addition, renal kallikrein activity and content were reduced in low-kallikrein rats. The latter group showed a greater ratio of heart weight to body wt both in basal conditions and after sodium loading. The ratio of kidney weight to body wt was reduced after sodium loading. These results indicate that a genetically-determined defect in urinary kallikrein excretion is associated with a greater blood pressure sensitivity to salt, possibly due to altered renal sodium handling.     

Promoting effect of monosodium aspartate, but not glycine, on renal pelvis and urinary bladder carcinogenesis in rat induced by N-butyl-N-(4-hydroxybutyl)nitrosamine

Although the incidences were relatively low, hyperplasias of the renal pelvis and the urinary bladder have been observed in Fischer-344 (F-344) rats after both sodium aspartate and glycine treatments in long-term 2-yr bioassays. In the present study, the effects of these amino acids on development of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-initiated urinary lesions were investigated in male and female F-344/DuCrj rats. F-344 rats of both sexes, 6 wk old at the commencement, were given 0.05% BBN for 4 wk and then treated with one of the amino acids at a level of 5.0% in the drinking water for the following 36 wk. Proliferative lesions in the renal pelvis often associated with necrosis and mineralization were increased in the group treated with BBN followed by sodium aspartate, but not by glycine, in both sexes. The same group demonstrated higher incidences of urinary bladder tumors with increased urinary pH and sodium concentration and decreased creatinine and uric acid, but not accompanying crystallization. These results showed a clear promoting effect of sodium aspartate for urinary carcinogenesis in rats. The mechanisms of the effect on the renal pelvis and urinary bladder might be different.     

The hepato-renal syndrome: renal amino acid transport in bile duct ligated rats (DL)--influence of treatment with triiodothyronine or dexamethasone on renal amino acid handling in amino acid loaded rats

The influence of triiodothyronine or dexamethasone on renal amino acid handling was investigated in anaesthetized, bile duct-ligated (DL) adult female rats. 3 days after DL, glomerular filtration rate (GFR) was unchanged whereas urine flow was decreased. Plasma concentrations of 5 out of 16 amino acids were significantly enhanced after DL. On the other hand, the fractional excretion (FE) of 11 out of 16 amino acids was significantly reduced as a sign of improved reabsorption capacity. Bolus injections of leucine (20 mg/100 g b.wt.), glutamine (45 mg/100 g b.wt.), or taurine (45 mg/100 g b.wt.) were followed by a temporary increase in the FE of the administered amino acids as well of the endogenous amino acids which were not administered. This phenomenon was more pronounced in DL than in control rats. Under load conditions, dexamethasone (60 microg/100 g b.wt.) or triiodothyronine (20 microg/100 g b.wt.) treatment for 3 days, i.p. once daily, was followed by a stimulation of renal amino acid reabsorption in DL rats. The increase in fractional amino acid excretion after amino acid load was significantly lower than in untreated rats. This effect was also more pronounced in DL rats.     

Renal toxicity and arterial hypertension in rats chronically exposed to vanadate

The effects of 1, 10, or 40 micrograms/ml of vanadium, given for six or seven months as sodium metavanadate in drinking water on cardiovascular and biochemical variables and the electrolyte metabolism of male Sprague-Dawley rats were investigated. At the end of the exposure period, all animals exposed to vanadate had increased systolic and diastolic blood pressure. This effect was not dose dependent and heart rate and cardiac inotropism were not affected. The role of defective renal function and electrolyte metabolism in such effects was supported, in the rats exposed to 10 and 40 ppm of vanadium, by the following changes: (a) decreased Na, + K(+)-ATPase activity in the distal tubules of nephrons; (b) increased urinary excretion of potassium; (c) increase in plasma renin activity and urinary kallikrein, kininase I, and kininase II activities; (d) increased plasma aldosterone (only in the rats treated with 10 ppm of vanadium). The alterations in the rats exposed to 1 ppm of vanadium were: (a) reduced urinary calcium excretion; (b) reduced urinary kallikrein activity; (c) reduced plasma aldosterone. These results suggest that blood hypertension in rats exposed to vanadate depends on specific mechanisms of renal toxicity related to the levels of exposure.