The effect of the anions, phosphate and sulphate, on normal rates of excretion of potassium in dogs.

Small doses of (NH4)2HPO4 or KH2PO4 by stomach tube caused increase in plasma PO4 and PO4 excretion. Above a threshold of 0-8 mmol. 1(-1), increase of plasma PO4 by 0-5 mmol. 1(-1) caused PO4 excretion to increase by about 35 mumol. min.-1 After KH2PO4 this relationship was not altered by the concurrent increases in plasma K and K excretion. After doses of (NH4)2SO4 or K2SO4, excretion of SO4 was similarly related to plasma SO4 and was independent of plasma K and K excretion. An effect of PO4 on K excretion was observed after doses of (NH4)2HPO4, when increased excretion of PO4 was accompanied by increased excretion of K without change in plasma K. There was also increased excretion of NH4 and a small increase in Na excretion. The changes were similar to those produced by (NH4)2SO4 [O'Connor and Summerill, 1976]. KH2PO4 and K2SO4 produced increase in plasma K and increased excretion of K not significantly different from the changes produced by KCl or KHCO3 [Baylis and O'Connor, 1976]. After KH2PO2 or K2SO4, the urinary anion was PO4 or SO4, instead of Cl and HCO3. Any effect of anions on K excretion was much less than the effect of increase in plasma K. At low rates of excretion of K, increased urinary excretion of impermeant anion can determine increased excretion of K. However, the effect of anion is small in comparison with the effect of increase in plasma K.     

The effect of plasma potassium in determining normal rates of excretion of potassium in dogs.

Doses of 5-15 mmol KCl or KHCO3 (less than the daily intake in food) given by stomach tube or intravenous infusion, produced increases in plasma K and in K excretion, the time delay between change in plasma K and rate of excretion being minimal. Without doses of K salts in control experiments, plasma K concentration was about 4 mmol/1 and K excretion about 5 mumol/min. After doses of KCl or KHCO3, plasma K and rate of excretion of K both increased, increase of 0-5 mmol/1 in plasma K being associated with an increase of about 35 mumo1/min in K excretion. Increased excretion of K was accompanied by a small increase in Na excretion. Excretion of both C1 and HCO3 increased, C1 more after HCO3 more after KHCO3. The results indicate that within normal ranges, plasma K is an important factor determining the rate of excretion of K.     

Stimulation of fecal fat excretion and the disposal of protoporphyrin in a murine model for erythropoietic protoporphyria

Erythropoietic protoporphyria (EPP) is characterized by toxic accumulation of the hydrophobic compound protoporphyrin (PP). Ferrochelatase-deficient (fch/fch) mice are an animal model for human EPP. Recently, we have demonstrated that the accumulation of another hydrophobic compound, unconjugated bilirubin, could effectively be treated by stimulation of fecal fat excretion. We investigated whether stimulation of fecal fat excretion enhanced the disposal of PP in fch/fch mice. Fch/fch mice were fed for 8 wk with a high-fat diet (16 wt% fat; control) or with the high-fat diet mixed with either a nonabsorbable fat (sucrose polyester) or the intestinal lipase inhibitor orlistat. The effects of the treatments on fecal excretion of fat and PP and on hepatic PP concentrations were compared with control diets. Fecal fat excretion in fch/fch mice on a high-fat diet was higher than in mice on a low-fat diet (+149%, P < 0.05). Sucrose polyesters and orlistat increased fecal fat excretion even more, up to sixfold of control values. However, none of the different treatments affected fecal PP excretion or hepatic PP concentration. Treatment of fch/fch mice with a high-fat diet, a nonabsorbable fat diet, or with orlistat increased the fecal excretion of fat but did not increase fecal PP excretion or decrease hepatic PP concentration. The present data indicate that accumulation of PP is not amenable to stimulation of fecal fat excretion.     

Urinary kallikrein in hypertensive animal models.

Urinary kallikrein excretion was studied in a number of animal models of hypertension. Kallikrein excretion was subnormal in spontaneously hypertensive rats as compared to Wistar/Kyoto rats and in rats made hypertensive by a clip on one renal artery. Kallikrein excretion was supranormal in rats made hypertensive by desoxycorticosterone and salt and in rats receiving desoxycorticosterone alone. It was subnormal after bilateral adrenalectomy. Kallikrein excretion increased in normotensive rats fed a low-sodium diet but was unchanged by a high-sodium diet. Thus, kallikrein excretion responded to changes in activity of sodium-retaining steroids and was not correlated with excretion of salt or water. In studies in dogs with stenosis of one renal artery kallikrein excretion was decreased on the stenoic side and the decrease correlated highly with the reduction in renal blood flow. While the role of the kallikrein-kinin system is still unclear the data indicate that the kidney may modify the initiation or maintenance of hypertension via this potent vasodilator system.     

Reduction of the effects of diuretics or sodium chloride loading in the conscious rat by inhibitors of prostaglandin synthesis

In conscious rats pretreatment with indomethacin or flurbiprofen, two chemically unrelated inhibitors of prostaglandin synthesis, reduced urine volume and sodium excretion induced by four diuretics, acetazolamide, amiloride, bendrofluazide and frusemide, or oral sodium chloride loads. The maximum reduction in sodium excretion was limited to approximately 2 mmol/kg Na⁺ even when sodium excretion was greatly increased. In contrast these inhibitors did not appreciably affect potassium excretion. These results indicate that part of the natriuretic response in the rat to highly and moderately efficacious diuretics and to sodium chloride loading is modified by prostaglandins. We suggest that the lack of effects on potassium excretion indicate that the collecting tubule is the probable site of action.     

Cholesterol catabolism in the rabbit in fasted and fed states.

Urinary and fecal endogenous steroid excretion of fed or fasted New Zealand white rabbits was determined by the isotopic steady state method after subcutaneous implantation of radioactive cholesterol. While plasma cholesterol was increasing during a 9-day fast, fecal steroid excretion decreased to 10% of the excretion rates in the fed state. Refeeding the fasted rabbits led to a decrease in plasma cholesterol and an increase in fecal endogenous steroid excretion. Urinary steroid excretion, which represented 18% of total endogenous steroid excretion for fed animals, decreased during fasting and increased during refeeding, but these changes were relatively small. The small intestine, cecum, and colon of fed or fasted rabbits had similar endogenous steroid was acidic steroid. During attempts to alter the circulating bile acid concentration by supplying deoxycholate (200 mg/day) to fed rabbits or cholestyramine (2 g/day) to fasted rabbits, plasma cholesterol concentration did not change to the same extent as during fasting or refeeding, respectively. The decreased cholesterol catabolism and the hypercholesterolemia that are seen in the fasting rabbit may result from decreased clearance of plasma cholesterol.     

De Novo Biosynthesis of Nicotinamide Adenine Dinucleotide in Escherichia coli: Excretion of Quinolinic Acid by Mutants Lacking Quinolinate Phosphoribosyl Transferase

The excretion of quinolinic acid was studied in growing and resting cells of Escherichia coli K-12 nadC(13). Under optimal conditions, this organism could synthesize quinolinic acid in several-fold excess of the amount which would be required for normal growth. The excretion of quinolinic acid was controlled by the concentration of nicotinamide adenine dinucleotide (NAD) precursors available to the organism either during growth or during incubation in dense cell suspensions. These observations suggest that biosynthesis of NAD de novo is regulated by both repression and feedback inhibition. Analogues of niacin which inhibit bacterial growth also inhibited and repressed the synthesis (excretion) of quinolinic acid. The pH optimum for quinolinic acid excretion agreed favorably with the optimum observed for its synthesis in vitro. The rate of quinolinic acid excretion was strongly influenced by the concentration of ribose or glycerol in the medium.     

Relationships among urinary kallikrein, mineralocorticoids and human hypertensive disease.

Urinary kallikrein excretion is reduced in patients with hypertension of unknown etiology. In addition, the excretion of this renal, kinin-forming enzyme was found to be elevated in hypertensive patients with primary aldosteronism. Aldosterone regulates kallikrein excretion, as normal subjects show increased kallikrein excretion in response to a low sodium intake, high potassium intake, or the synthetic mineralocorticoid, fludrocortisone, whereas kallikrein excretion falls during treatment with spironolactone. The relationship between kallikrein excretion and aldosterone activity may directly reflect the intrarenal activity of the kallikrein-kinin system, as determined by studies of kallikrein levels from isolated renal cells or of plasma kinin levels in man in response to postural changes or saline loads. Some patients with essential hypertension do not show a normal increase in kallikrein excretion in response to low dietary sodium intake despite an apparently normal aldosterone response, suggesting that there may be a defect in the renal kallikrein-kinin system in these patients. Whether these findings are of pathogenetic significance in human hypertensive disease remains to be determined.     

Capillary gas chromatography as a tool for characterization of urinary steroid excretion in patients with congenital adrenal hyperplasia

Urinary steroid excretion was studied by capillary gas chromatography in 23 patients with congenital adrenal hyperplasia. In 5 patients the estimated excretion rates of pregnanetriol were in or below the normal range and 7 patients presented supranormal excretion rates of tetrahydro-cortisone and/or other glucocorticoid metabolites. Deficiency of 21-hydroxylase was nevertheless demonstrated in each patient by an increased ratio of excreted precursors vs products of 21-hydroxylase, e.g. of pregnanetriol/tetrahydro-cortisone. Due to this relative deficiency of glucocorticoids the patients' steroid excretion was further characterized by a predominance of 5 alpha-hydrogenated C19O3 metabolites (11-keto-androsterone, 11-hydroxy-androsterone) over their 5 beta-hydrogenated homologues (11-keto-etiocholanolone, 11-hydroxy-etiocholanolone). An apparent preponderance in the excretion of pregnenetriol over that of pregnanetriol was found in 4 patients, but the presence of pregnenetriol was not confirmed by mass spectrometry following prepurification of the urine samples by thin-layer chromatography indicating interference of an unidentified steroid metabolite with the initial gas chromatographic analysis. The simultaneous determination of steroids serving as precursors or products of 21-hydroxylase by capillary gas chromatography helps to establish the diagnosis of 21-hydroxylase deficiency and to characterize the pattern of steroid excretion in this syndrome even in patients where the estimation of single urinary steroids may lead to erroneous conclusions.     

Renal excretion of long term sulfonamides under fluid administration and modification of the urinary pH value]

The renal excretion of sulfaclomide, sulfamerazine and sulfamethoxypyridazine is delayed by increased fluid application in rats. The simultaneous administration of sulfonamides and ammonium chloride or sodium hydrogen carbonate causes, respectively, retardation and acceleration of renal sulfonamide excretion which is consistent with the change in urinary pH value. The retarded renal sulfonamide excretion with increasing diuresis is explained by the ensuing change in the urinary pH value. For clinical uses, a speedy renal excretion of long-time sulfonamides by increased diuresis can be expected only if alkalization of the urine is achieved at the same time.     

Effect of probenecid on the urinary excretion of TXB2 and PGE2 in the anaesthetised rat

In the anaesthetised rat, probenecid (33 mg/kg) produced a 50% fall in urinary TXB2 excretion indicating that a component of the TXB2 excreted in the urine is secreted by the proximal tubule. At a higher dose of probenecid (100 mg/kg) this effect was overcome, a relative increase in urinary TXB2 excretion being produced. This may provide evidence for the proximal reabsorption or bi-directional transport of TXB2 in the rat. At 100 mg/kg probenecid also produced an 8-fold increase in urinary PGE2 excretion. Although the bi-directional transport of PGE2 is well known, this is the first time urinary PGE2 excretion rate has been shown to be modified by probenecid. The increase in PGE2 excretion could obscure the assessment of any inhibition by probenecid of proximal PGE2 secretion. It could also provide evidence for the proximal reabsorption of PGE2. However the interpretation of probenecid-induced changes in eicosanoid excretion in terms of modified tubular reabsorption must be treated with caution since urinary eicosanoid excretion could be increased by other properties of probenecid including inhibition of either protein binding or the uptake of eicosanoids into the lung.     

The effect of gonadectomy and aromatase inhibition on the excretion of 19-nordeoxycorticosterone in rats

19-Nordeoxycorticosterone (19-norDOC) is a powerful mineralocorticoid, which has been postulated to be involved in the pathogenesis of some forms of hypertension. The urinary excretion of 19-norDOC by female rats is up to 20 times that of males. To demonstrate the influence of the gonads on the excretion of 19-norDOC, we measured the excretion of 19-norDOC in intact and gonadectomized male and female rats with and without replacement with testosterone (40 mg testosterone enanthate s.c.) or estrogen (4 mg estradiol valerate s.c.) and in intact animals receiving the aromatase inhibitor, 10-propargyl androstenedione (10-pA) (10 mg s.c.). Orchiectomy produced a significant increase in the urinary excretion of 19-norDOC in males. Testosterone treatment decreased 19-norDOC excretion by castrated males to below intact values, while estrogen administration increased its excretion. Oophorectomy had no consistent effect on 19-norDOC excretion. In oophorectomized females, testosterone administration significantly suppressed 19-norDOC excretion and estrogen replacement increased excretion slightly. 10-pA had little effect on the excretion of 19-norDOC in intact rats of either sex. In conclusion, it appears that 19-norDOC production is inhibited by testosterone, but is affected only slightly by estrogens.     

Pendrin in the mouse kidney is primarily regulated by Cl- excretion but also by systemic metabolic acidosis

The Cl(-)/anion exchanger pendrin (SLC26A4) is expressed on the apical side of renal non-type A intercalated cells. The abundance of pendrin is reduced during metabolic acidosis induced by oral NH(4)Cl loading. More recently, it has been shown that pendrin expression is increased during conditions associated with decreased urinary Cl(-) excretion and decreased upon Cl(-) loading. Hence, it is unclear if pendrin regulation during NH(4)Cl-induced acidosis is primarily due the Cl(-) load or acidosis. Therefore, we treated mice to increase urinary acidification, induce metabolic acidosis, or provide an oral Cl(-) load and examined the systemic acid-base status, urinary acidification, urinary Cl(-) excretion, and pendrin abundance in the kidney. NaCl or NH(4)Cl increased urinary Cl(-) excretion, whereas (NH(4))(2)SO(4), Na(2)SO(4), and acetazolamide treatments decreased urinary Cl(-) excretion. NH(4)Cl, (NH(4))(2)SO(4), and acetazolamide caused metabolic acidosis and stimulated urinary net acid excretion. Pendrin expression was reduced under NaCl, NH(4)Cl, and (NH(4))(2)SO(4) loading and increased with the other treatments. (NH(4))(2)SO(4) and acetazolamide treatments reduced the relative number of pendrin-expressing cells in the collecting duct. In a second series, animals were kept for 1 and 2 wk on a low-protein (20%) diet or a high-protein (50%) diet. The high-protein diet slightly increased urinary Cl(-) excretion and strongly stimulated net acid excretion but did not alter pendrin expression. Thus, pendrin expression is primarily correlated with urinary Cl(-) excretion but not blood Cl(-). However, metabolic acidosis caused by acetazolamide or (NH(4))(2)SO(4) loading prevented the increase or even reduced pendrin expression despite low urinary Cl(-) excretion, suggesting an independent regulation by acid-base status.     

Triamcinolone activation of renal ammonia production.

The effects of scillaren and dinitrophenol on bilirubin excretion by the perfused rat liver were studied. Both compounds inhibited bile flow, scillaren by 20 to 40%, and dinitrophenol by 60 to 80%. Bilirubin excretion was also impaired. However, the effect of scillaren on bilirubin excretion was less than that on bile flow, as indicated by an increase in the bile bilirubin concentration, whereas dinitrophenol had a greater effect on bilirubin excretion than on bile flow. Dinitrophenol also inhibited the hepatic removal of unconjugated bilirubin from the perfusate, probably because it impaired the initial uptake and/or storage of unconjugated bilirubin by the perfused liver.     

Circadian rhythms of urinary electrolyte excretion in freely moving rats

In 8 freely moving rats the circadian variation in the eletrolyte excretion was studied. Food was available during either the dark or the light period. The lights were on from 0800–2000 hr. Potassium, phosphate and magnesium showed peak excretion values during the dark period under both feeding conditions, although the maxima occurred 2.5 hr earlier when the rats were fed during the light period; minimum excretion was recorded just prior to feeding. Sodium excretion followed a different pattern; for animals fed during the night, maximum excretion occurred almost at the end of the dark period and minimum excretion at the start of the feeding period. For day-fed animals these values were recorded 5 and 4 hours earlier, respectively. Calcium excretion reached a maximum after the feeding period and a minimum shortly after the onset of feeding. From this study it can be concluded that the peak excretions of potassium, phosphate and magnesium are only slightly influenced by the feeding regimen, indicating that they depend mainly on an endogenous rhythm. In contrast, the minimum excretion of these ions is determined by feeding. For calcium maximum as well as minimum excretion is correlated with the feeding regimen. The excretion pattern of sodium differs from that of calcium, as well as potassium, phosphate and magnesium, indicating that it is controlled by a different mechanism.     

Biliary amino acid excretion in rats before and after bilateral nephrectomy.

In previous studies it could be shown that after bilateral nephrectomy (NX) the excretory function of the liver is disturbed. To further clarify whether or not this "renohepatic syndrome" is caused by toxic effects of uremia or by competition phenomena between various uraemic toxins an additional aspect was investigated: the biliary excretion of endogenous amino acids. Furthermore, previously it could be shown that renal and hepatic excretory functions overlap. Therefore, the renal excretion of effectively biliary eliminated amino acids (glutamic acid, alanine, tyrosine, isoleucine) is very low and vice versa. That means, that the renal excretion of amino acids with low hepatic elimination (tryptophan, citrulline, lysine, taurine) dominates. The hepatic excretion of amino acids is hardly altered after NX. Remarkably, the removal of both kidneys is followed by a distinct reduction in amino acid plasma concentrations, especially if these concentrations are relatively high in the controls. Interestingly, there is no correlation between plasma concentrations and biliary excretion of amino acids. But the calculation of the bile to plasma concentration ratios of amino acids makes it possible to differentiate three groups of amino acids: Amino acids excreted actively into bile (ratio > or = 1), amino acids with ratios below 1, indicating effective retention, and amino acids with ratios of about 1, whose hepatic handling is passive. After NX these ratios tended to approach 1; low ratios increased and high ratios decreased. That means, active processes involved in excretion or retention are obviously disturbed. These changes could indicate uraemic liver damage as proved regarding influence of NX on hepatic excretion of other endogenous substances and xenobiotics.     

Excretion of electrolytes, free cortisol and aldosterone-18-oxo-glucuronide in 24-hr urines of the Mongolian gerbil (Meriones unguiculatus): effect of lysine-vasopressin and adrenocorticotrophin administration, and of changes in sodium balance

1. Administration of lysine-vasopressin (LVP, 1 IU/animal) strongly reduced electrolyte excretion in 24 hr urines of adult male Mongolian gerbils, but had no effect on free cortisol (C) or aldosterone-18-oxo-glucuronide (Aldo-gluc.) excretion. 2. (1-24) ACTH, given at a dosage of 20 IU/animal, increased C and Aldo-gluc. excretion but did not influence electrolyte excretion. 3. Fluid intake and potassium excretion were decreased in animals offered a control or a sodium-deficient diet; contrasting, excretion of C was stimulated. 4. In contrast to other rodents, Aldo-gluc. excretion showed no changes in Mongolian gerbils offered a sodium-deficient diet, but was diminished in animals either fed a control diet or given saline (154 mmol/l) as drinking water.     

Factors influencing nitrogen and phosphorus excretion rates of fish in a shallow lake

Summary 1. Fish excretion can be an important source of nutrients in aquatic ecosystems. Nitrogen (N) and phosphorus (P) excretion rates are influenced by many factors, including fish diet, fish growth rate and fish size. However, the relative influence of these and other factors on community‐level excretion rates of fish is unknown. 2. We used bioenergetics modeling to estimate excretion rates of eight fish species in a shallow, Minnesota (U.S.A.) lake over four months in both 2004 and 2005. Excretion rates of each species were summed for community‐level N and P excretion rates, as well as the N : P ratio of excretion. We then used a model‐selection approach to assess ability of independent variables to predict excretion rates, and to identify the most parsimonious model for predicting N : P excretion ratios and P and N excretion rates at the community scale. Predictive models were comprised of the independent variables water temperature and average fish density, fish size, fish growth rate, nutrient content of fish and nutrient content of fish diets at the community scale. 3. Fish density and nutrient content of fish diets (either N or P) were the most parsimonious models for predicting both N and P excretion rates, and explained 96% and 92% of the variance in N and P excretion, respectively. Moreover, fish density and nutrient models had 1400‐fold more support for predicting N and 21‐fold more support for predicting P excretion relative to models based on fish density only. Water temperature, fish size, fish growth rates and nutrient content of fish showed little influence on excretion rates, and none of our independent variables showed a strong relationship with N : P ratios of excretion. 4. Past work has focused on the importance of fish density as a driver of fish excretion rates on a volumetric basis. However, our results indicate that volumetric excretion rates at the community scale will also change substantially in response to changes in relative abundance of fish prey or shifts in relative dominance of planktivores, benthivores, or piscivores. Changes in community‐scale excretion rates will have subsequent influences on algal abundance, water clarity, and other ecosystem characteristics.     

Comprehensive analysis of mechanism underlying hypouricemic effect of glucosyl hesperidin

Hyperuricemia is caused by hepatic overproduction of uric acid and/or underexcretion of urate from the kidneys and small intestine. Although increased intake of citrus fruits, a fructose-rich food, is associated with increased risk of gout in humans, hesperidin, a flavonoid naturally present in citrus fruits, reportedly reduces serum uric acid (SUA) levels by inhibiting xanthine oxidase (XOD) activity in rats. However, the effects of hesperidin on renal and intestinal urate excretion were previously unknown. In this study, we used glucosyl hesperidin (GH), which has greater bioavailability than hesperidin, to clarify comprehensive mechanisms underlying the hypouricemic effects of hesperidin in vivo. GH dose-dependently decreased SUA levels in mice with hyperuricemia induced by potassium oxonate and a fructose-rich diet, and inhibited XOD activity in the liver. GH decreased renal urate excretion without changes in kidney URAT1, ABCG2 or GLUT9 expressions, suggesting that reducing uric acid pool size by inhibiting XOD decreased renal urate excretion. We also found that GH had no effect on intestinal urate excretion or protein expression of ABCG2. Therefore, we concluded that GH exhibits a hypouricemic effect by inhibiting XOD activity in the liver without increasing renal or intestinal urate excretion. Of note, this is the first study to elucidate the effect of a flavonoid on intestinal urate excretion using a mice model, whose findings should prove useful in future food science research in the area of urate metabolism. Taking these findings together, GH may be useful for preventing hyperuricemia, especially in people with the overproduction type.     

中华绒螯蟹在不同pH值环境下的氮排泄

研究不同pH值环境对中华绒螯蟹（Eriocheir sinensis）氮排泄的影响。本研究采用直接浸浴法测定中华绒螯蟹在pH值4．5，6．0，7．5，9．0和10．5条件下的氮排泄。结果表明，在pH值9．0及其以下时，氨氮排泄无显著变化，当pH值升高到10．5时，氨氮排泄急剧下降，其排泄过程具有不连续性；亚硝酸氮、尿素氮和有机氮的排泄随pH值的升高而增加；硝酸氮的排泄同亚硝酸氮类似，但在pH值10．5时，呈下降状态；总氮的排泄随pH值升高而降低。在pH值4．5时，中华绒螯蟹的氨氮排泄量占总氮排泄量的91．0％，随着pH值上升，氨氮占总氮排泄的比例下降，而包括有机氮在内的其它形式的含氮化合物的排泄比例上升。因此．我们认为当环境pH值在9．0以下的范围波动时，不会对中华绒螯蟹的氨氮排泄带来不利影响，但过高的pH值可能会阻碍氮排泄。