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Urinary transforming growth factor-beta excretion in patients with hypertension, type 2 diabetes, and elevated albumin excretion rate: effects of angiotensin receptor blockade and sodium restriction.

OBJECTIVE: Transforming growth factor-beta (TGF-beta) is a prosclerotic growth factor implicated in the pathogenesis of diabetic nephropathy. In addition to high glucose, other factors implicated in renal fibrosis and increased TGF-beta synthesis include angiotensin II and high dietary sodium intake. The aim of this study was to examine the effect of angiotensin receptor blockade (ARB) and dietary sodium restriction on the plasma concentration and urinary excretion of TGF-beta in hypertensive patients with type 2 diabetes and elevated albumin excretion rate (AER). RESEARCH DESIGN AND METHODS: Twenty-one subjects with hypertension and AER between 10 and 200 microg/min were randomized to receive either 50 mg losartan daily (n = 11) or placebo (n = 10). Drug therapy was given in two 4-week phases, separated by a 4-week washout period. In the last 2 weeks of each phase, patients were assigned to regular- or low-sodium diets in random order. Parameters measured at week 0 and 4 of each phase included plasma TGF-beta concentration, TGF-beta urinary excretion, AER, clinic mean arterial blood pressure, and urinary sodium excretion. RESULTS: Plasma TGF-beta was unaffected by losartan treatment or sodium intake. In the losartan group, urinary TGF-beta excretion decreased by 23.2% (-39.2 and 13.6) [median (interquartile range)] and 38.5% (-46.8 and -6.1) in the regular- and low-sodium phases, respectively (P < 0.05 for drug effect). In the placebo group, median changes of 0.0% (-12.1 and 44.4) and 0.0% (-29.2 and 110.7) occurred in the regular- and low-sodium phases, respectively. Sodium restriction did not affect urinary TGF-beta excretion in either losartan- or placebo-treated patients (P = 0.54 for overall dietary effect), and there was no evidence of interaction between drug and diet (P = 0.29). CONCLUSIONS: In hypertensive type 2 diabetic patients with elevated AER, the ARB losartan, but not sodium restriction, reduced urinary TGF-beta excretion. These data suggest that the renoprotective effects of losartan in patients with type 2 diabetes and nephropathy may include a reduction in renal TGF-beta production.

Albuminuria↗

Association between urinary albumin excretion and serum dehydroepiandrosterone sulfate concentration in male patients with type 2 diabetes: a possible link between urinary albumin excretion and cardiovascular disease.

OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in patients with type 2 diabetes. Both elevated urinary albumin excretion and low serum concentrations of dehydroepiandrosterone (DHEA) are associated with increased CVD mortality. This raises the possibility of DHEA as a causal intermediate linking urinary albumin excretion to CVD. RESEARCH DESIGN AND METHODS: Relationships of urinary albumin excretion to serum DHEA sulfate (DHEA-S) concentration and to major cardiovascular risk factors, including blood pressure, serum lipid concentration, glycemic control (HbA1c), and BMI, were investigated in 357 consecutive men with type 2 diabetes. RESULTS: Serum DHEA-S concentrations were lower in patients with macroalbuminuria (866.5 +/- 523.8 ng/ml, P <0.0001) and in those with microalbuminuria (1,014.4 +/- 525.3 ng/ml, P=0.0006) than in patients with normoalbuminuria (1,232.6 +/- 542.4 ng/ml). Serum DHEA-S concentration correlated inversely with log (urinary albumin excretion) (r=-0.227, P <0.0001). Multiple regression analysis demonstrated that duration of diabetes (beta=0.147, P=0.0075), HbA1c (beta=0.156, P=0.0048), BMI (beta=0.194, P=0.0007), systolic blood pressure (beta=0.195, P=0.0005), and serum DHEA-S concentration (beta=-0.192, P=0.0010) were independent determinants of log (urinary albumin excretion). CONCLUSIONS: Serum DHEA-S concentration, which correlated inversely with degree of urinary albumin excretion, may contribute to the link between elevated urinary albumin excretion and higher CVD mortality in male patients with type 2 diabetes.

Age of Onset↗

Biliary and urinary excretion of drug conjugates: effect of diuresis and choleresis on excretion of harmol sulphate and harmol glucuronide in the rat.

1. Harmol (7-hydroxy-1-methyl-9H-pyrido [3,4b] indole) is converted to harmol sulphate and harmol glucuronide in the rat in vivo. Harmol sulphate is excreted mainly in urine, while harmol glucuronide is excreted about equally in bile and urine, when harmol is given intravenously. 2. In rats with ligated kidneys, only choleresis produced by glycodehydrocholate and dehydrocholate caused enhanced biliary excretion of harmol sulphate; harmol glucuronide was unaffected. Several other bile salts had no effect. 3. Mannitol diuresis markedly increased urinary excretion of harmol sulphate, and decreased its biliary excretion. Harmol glucuronide was much less affected. 4. Nafenopin pretreatment increased liver weight and bile flow, and enhanced biliary excretion of harmol sulphate at the expense of its urinary excretion. 5. For harmol sulphate, urine and bile are compensatory pathways of elimination that can be influenced by urine and bile flow changes through diuresis and choleresis.

Alkaloids↗

Enhancement of tetrathiomolybdate-induced biliary copper excretion in sheep by general anaesthesia and the effect on copper excretion in urine and bile.

To determine whether copper removed from the liver by tetrathiomolybdate (TTM) but not excreted in bile, is excreted in saliva or urine, the effect of an intravenous injection of 100 mg of TTM, as ammonium tetrathiomolybdate, on copper excretion by these routes was measured in conscious sheep and sheep maintained under general anaesthesia. During 4.5 hours the total amount of copper excreted in bile in the untreated, conscious animal was 0.52 +/- 0.04 mumols (mean +/- SE). A dose of 100 mg TTM increased excretion by an average of 11.7-fold to 6.06 +/- 0.29 mumols. Under halothane or barbiturate general anaesthesia copper excretion was increased 3.4-fold to 1.78 +/- 0.30 mumols. In anaesthetised sheep 100 mg TTM produced a 40.7-fold increase to 21.18 +/- 0.95 mumols. Neither anaesthesia nor TTM caused any increase in copper excretion in saliva or urine.

Anesthesia, General↗

Low urinary dopamine excretion associated to low sodium excretion in normotensive Piaroa Amazonian ethnia compared to urban subjects.

The objective of this work was to compare urinary dopamine, noradrenaline, adrenaline, sodium and potassium excretion in a group of normotensive Piaroa Amazonic ethnia who do not use salt in their regular food intake, against a group of urban normotensive citizens known to have a high salt intake in their regular meals. Twenty adult normotensive Piaroa subjects living in the Amazonas forest, 11 men and 9 women, 23-72 years old, and 33 normotensive urban citizens, 25-70 years old, 17 men and 17 women, were included in the study. After a 10 min. rest, an average of three supine systolic (SBP) and diastolic (DBP) blood pressure recordings was obtained. Piaroas subjects SBP and DBP were 111.3 +/- 2.9 mmHg and 62.7 +/- 1.9 mmHg respectively; urban subjects SBP and DBP were 111.8 +/- 2.2 mmHg and 70.3 +/- 1.6 mmHg respectively. Supine heart rate was lower in Piaroas (58.0 +/- 1.8 beats/min) than in urban subjects (76.5 +/- 1.9 beats/min), p < 0.05. Sodium urinary excretion was much lower in Piaroas (12.6 +/- 5.2 mmol/24 h) when compared to urban subjects (210.7 +/- 24.5 mmol/24 h), p < 0.01. No difference was found in daily urinary potassium excretion between Piaroas and urban subjects (50.4 +/- 7.2 mmol/24 h vs 45.1 +/- 7.4 mmol/24 h). Urinary dopamine excretion was lower in Piaroas (314.7 +/- 40.1 micrograms/24 h) in comparison to urban subjects (800.4 +/- 59.2 micrograms/24 h), p < 0.05. Daily urinary noradrenaline and adrenaline excretion were 67.9% and 85.4% respectively lower in Piaroas than in urban subjects. In conclusion, lower amounts of sodium daily intake are associated to lower kidney dopamine production in Piaroas as compared to urban subjects. Apparently indigenous tribes might require less kidney dopamine synthesis to excrete the very small amounts of salt they consume in their regular food intake. The opposite was found in urban subjects; more kidney dopamine synthesis would be required for larger amounts of urinary sodium excretion. In this population, essential hypertension has been associated to a failure of the natriuretic mechanism triggered by dopamine onkidney tubules.

Adult↗

Estimation of bile acid excretion in man: comparison of isotopic turnover and fecal excretion methods.

Bile acid excretion was studied in 9 human subjects simultaneously by the Lindstedt (Lindstedt, S. 1957. Acta Physiol. Scand. 40:1-9) isotopic turnovermethod and by fecal chemical analysis during a balance study. The identities of the fecal bile acids were confirmed by combined gas-liquid chromatography/mass spectrometry. Under the steady state conditions of the patient studies, bile acid excretion values obtained by fecal analysis were lower (by 18.1 to 44.2%) than the values obtained by the isotopic turnover method. This difference persisted even in those patients given [14C]chenodeoxycholic acid instead of [3H]chenodeoxycholic acid. The fecal excretion values were similar when calculated using either beta-sitosterol or chromium sesquioxide as fecal flow markers. The fecal excretion values during the earlier part of the isotopic study were higher than those during the latter part of the study. The lower values of bile acid excretion obtained from fecal analysis could not be explained by the loss of bile acids as sulfate conjugates or by losses due to bile acid degradation in the intestine. This study suggests that bile acid turnover is consistently higher than bile acid excretion under experimental conditions. It is recommended that the data obtained from the isotopic turnover method should not be compared with fecal excretion data.

Adult↗

Peripartal excretion of Eimeria oocyst by cows on Swedish dairy farms and the age of calves at first excretion.

Faecal samples were collected 3 times a week for 6 weeks from 22 paripartal cows and for up to 15 weeks after birth from 27 calves in 3 herds, to determine the numbers of Eimeria oocysts excreted and the age at which the calves first excreted oocysts. Only low numbers of oocysts were excreted by the cows and no oocysts were detected in 93% of the samples. However, half the cows excreted oocysts at least once. The age at which the calves first excreted oocysts ranged from 2.5 to at least 15 weeks, and there was a significant difference between the herds in their mean age at first excretion. Oocysts of Eimeria alabamensis, E. auburnensis, E. bovis and E. ellipsoidalis were found in numbers ranging from 7 to 8450 oocysts per gram faeces. About 50% of the calves excreted oocysts before they were transferred to group pens. The primary source of infection of the calves was probably their penmates or the previous occupants of the pens, and the cows probably played a subsidiary role.

Age Factors↗

Urinary estradiol-17 beta excretion in common marmosets, Callithrix jacchus: diurnal pattern and relationship between creatinine-related values and excreted amount.

1. The diurnal pattern of urinary estradiol and creatinine excretion was investigated in order to evaluate the relationship between total estradiol excretion per day and the estradiol concentration or the estradiol-to-creatinine ratio from single urine samples in female common marmosets (Callithrix j. jacchus). 2. During a 36-day period, urine was collected from five adult female marmosets in 3-hr intervals during the light time of an LD 12:12 (400:0.1 lx) which corresponded to the animals' activity time. 3. Estradiol concentration was determined by radioimmunoassay after glucuronidase treatment and creatinine concentration was measured photometrically. 4. Concentration and amount of excreted estradiol, and the creatinine concentration showed a distinct diurnal pattern with significantly higher levels at the beginning of the activity time compared to later sampling times. 5. No diurnal pattern was present in the estradiol-to-creatinine ratio, but the difference between lower follicular and higher luteal phase levels of estradiol excretion remained significant in the 36-day period. 6. Correlation analyses revealed significantly positive correlations between the total estrogen mass excreted per day and the estradiol-to-creatinine ratio in "morning urine" samples. 7. Thus the estradiol-to-creatinine ratio of single urine samples collected at the beginning of the activity time provides a reliable estimate of total estrogenic output in this species. 8. Studies of the circadian pattern of urinary hormone excretion, however, require total urine sampling.

Animals↗

Relation between renal and hepatic excretion of drugs. II. Age-dependence of phenol red excretion in comparison with those of p-aminohippurate and indocyanine green.

The excretory functions of kidney and liver do not develop simultaneously during the maturation of an individual. Therefore age related differences in the relation between renal and hepatic drug excretion could be expected. In this study the excretion of p-aminohippurate (PAH) and indocyanine green (ICG) as model substances for nearly exclusive excretion via kidney or liver, respectively, have been compared with that of phenol red eliminated both via kidneys and liver (3:1). Experiments were performed on rats between the 10th and 105th days of life. For PAH and ICG the typical age courses of renal or hepatic excretion have been confirmed. Both urinary and biliary phenol red excretion show an influence of age, however, renal elimination reaches adult values as early as at the 20th day of life. Furthermore the age relation concerning compensation of the loss of kidney or liver excretory functions has been studied. Neither after nephrectomy (NX) nor after bile duct ligation (DL) the PAH or ICG elimination via the alternative pathway, respectively, were quantitatively increased. Thus a compensation of the interruption of the main elimination route does not occur in all ages. In contrast, phenol red excretion into urine and bile increases distinctly after DL or NX. This increase becomes even significant after administration of suitable doses of phenol red saturating transport capacities of liver or kidney. The compensation is first of all caused by passive pharmacokinetic changes. Active compensatory mechanisms have not been proved.

Aging↗

Water intake and excretion, urinary solute excretion and some stress indicators in mink (Mustela vison): effect of ambient temperature and quantitative water supply to lactating females.

Lactation is a physiologically demanding period in mink production, during which kit and dam losses may occur. Ambient temperature and quantitative water supply are thought to affect animal performance and well-being, but conclusive data in the literature are sparse. Therefore, effects of ambient temperature (Ta; low, about 5 degrees; medium, about 15 degrees; high, average 20-25 degrees) and water supply (ad libitum (N), or 10% extra supplementation in the food (E)) were investigated regarding effects on quantitative water intake and excretion, urine osmolality and solute excretion, and urinary cortisol and catecholamines as stress indicators in an experiment with twelve lactating mink with litters of three to seven kits in three consecutive periods, lasting 3, 3 and 2 d respectively. Kit ages ranged from 15 to 20 d at the end of the experiment. Water requirement for milk production (factorial calculations) and water available for evaporation (balance component) were estimated. Period, and hence mainly Ta, had a significant influence on intake of metabolizable energy, quantitative water intake and excretion, but there was less effect of water supply. The total water intake and excretion were very high in relation to the weight of the animals as an effect of lactation. Water intake and excretion, and urinary Na excretion, seemed to be less accurately regulated compared with corresponding functions in non-lactating animals. Rectal temperature increased with increasing Ta, possibly as a means of decreasing evaporative water loss. Water output in milk was estimated to increase from 118 g/d at low Ta to 134 g/d at high Ta. The amounts of water available for evaporation were estimated to be 42, 58 and 69 g/kg0.75 at low, medium and high Ta. Cortisol data did not indicate that the animals experienced negative stress. It was concluded that prolonged periods of high Ta may be hazardous for lactating mink because of decreased intake of metabolizable energy resulting in energy deficit and excessive mobilization of body reserves simultaneously as the requirement for intake of water increases considerably.

Analysis of Variance↗

Effects of interactions between drugs on the renal excretion of trientine in rats--acetazolamide and furosemide increase trientine excretion.

PURPOSE: To elucidate the effects of drug interactions on the urinary excretion of trientine in rats. METHOD: Trientine and various other drugs were intravenously administered to rats and the urinary excretion of trientine was investigated. To clarify the mechanisms of drug-drug interactions, we also investigated the effects of various drugs on spermine uptake by rat renal brushborder membrane vesicles. RESULTS: Cimetidine, a substrate of the H+/organic cation antiporter, and aminoglycoside antibiotics did not affect trientine excretion, while acetazolamide and furosemide, which increase the concentration of sodium ions in renal proximal tubules, increased the excretion of trientine. However, trichlormethiazide, which acts in renal distal tubules, did not affect trientine excretion. Acetazolamide and furosemide did not directly affect the Na+/spermine transporter because these diuretics had no effect on the uptake of spermine into the rat renal brush-border membrane vesicles. CONCLUSIONS: There is no interaction between trientine and the substrate of the H+/organic cation antiporter or aminoglycoside antibiotics. However, drugs that change the concentration of sodium ions in renal proximal tubules, such as diuretics, can increase the trientine excretion since the increase in the luminal concentration of sodium ion accelerates the Na+/spermine antiporter.

Acetazolamide↗

Increased urinary nitrite excretion in primary enuresis: effects of indomethacin treatment on urinary and serum osmolality and electrolytes, urinary volumes and nitrite excretion.

OBJECTIVE: To assess urinary nitrite excretion, a stable end product of nitric oxide (NO), in patients with enuresis and in normal controls, and to evaluate the effects of indomethacin (a potent prostaglandin synthesis inhibitor) on urinary nitrite excretion, other urinary variables and bladder capacity. PATIENTS AND METHODS: The study comprised 10 patients with primary enuresis and 10 normal comparable controls (age range 6-14 years). Nitrite was assayed in 'spot' morning urine samples in both the enuretics and normal controls. Enuretics were then given 50 mg indomethacin suppositories each night; urine volume, urinary osmolality and electrolytes, serum osmolality and electrolytes and urinary nitrite were assayed before indomethacin treatment and after 15 days of treatment. RESULTS: The mean (sd) urinary nitrite excretion was 24.4 (19.6) micromol/L in normal children and 275.9 (111.2) micromol/L in enuretics (P<0.05). With indomethacin, the urinary nitrite concentration was significantly decreased to 141 (45.1) micromol/L (P<0.05) and associated with a significant reduction in bed-wetting episodes and voiding frequency. The functional bladder capacity was <70% of the predicted value for age in six of the patients; they had significant improvements on indomethacin, to values similar to those in patients with a nearly normal functional bladder capacity. Indomethacin decreased the 24-h urinary volume by 41%, the night volume by 40%, clearance of free water by 46% and increased the day : night urinary volume ratio by 55%. The absolute amounts of urinary calcium, magnesium, phosphorus, urea, creatinine, and glucose were lower on indomethacin, although not statistically significantly so. Indomethacin decreased the 24-h urinary and 'spot' morning osmolality and osmotic clearance. There were no significant changes in serum osmolality and electrolyte concentrations. Indomethacin also decreased the absolute amount of urinary sodium, chloride and potassium, fractional sodium and potassium excretion, and filtered sodium. Creatinine clearance was decreased by 20% (P>0.05) and normal 24-h urinary protein was significantly lower, by 47%, after indomethacin treatment (P<0.05). CONCLUSION: Urinary nitrite excretion increased significantly in patients with primary nocturnal enuresis; indomethacin markedly reduced bed-wetting episodes and decreased the frequency of voiding in enuretics with small or normal functional bladder capacity, which was associated with a significant decrease in urinary nitrite excretion. Indomethacin reduced bed-wetting by decreasing the urine volume, clearance of free water and urinary electrolytes, and through possible effects on bladder and urethral contraction, by inhibiting NO and prostaglandin synthesis. NO and prostaglandins might be important in the pathogenesis of primary enuresis.

Adolescent↗

Excretion of purine derivatives by ruminants: effect of exogenous nucleic acid supply on purine derivative excretion by sheep.

The present study examined the relationship between the supply of exogenous nucleic acid (NA) purines and their recovery as the derivatives hypoxanthine, xanthine, uric acid and allantoin in urine. Six lambs, totally nourished by intragastric infusions of volatile fatty acids (VFA) and casein (i.e. no rumen fermentation), were given by abomasal infusion a microbial NA concentrate at six levels (from zero to 24.5 mmol purines/d). The true digestibility between the abomasum and terminal ileum of the NA purines was measured in a separate experiment using three lambs. The relative proportion of urinary allantoin increased, and that of other derivatives decreased, as the amount of NA infused was increased. The relationship between total excretion of purine derivatives (Y; mmol/d) and exogenous purines absorbed (X; mmol/d) was Y = 0.84X + 0.150W0.75 e-0.25X, where W is body-weight (kg). This implies that the endogenous contribution to the total excretion of derivative decreased as the supply of exogenous purines increased, with an associated progressive replacement of de novo synthesis by exogenous purines. The model also implies that 0.16 of the purines were eliminated through routes other than derivative excretion in urine. Once excretion exceeded 0.6 mmol/kg W0.75 per d, endogenous excretion was effectively zero and thus Y = 0.84 X. In normally fed sheep, derivative excretion should therefore relate to the microbial purines and, hence, microbial protein absorbed according to these models. The changing proportions of allantoin and other derivatives in urine were probably due to changes in the relative importance of endogenous and exogenous purines as precursors.

Allantoin↗

Urinary chromium excretion, diurnal changes, and relationship to creatinine excretion in healthy and sick individuals of different ages.

Since urine is the main excretory pathway for chromium, this study was conducted to compare in normal individuals the daily urinary chromium excretion with a 4 hr sample, to investigate diurnal fluctuations of urinary chromium and age-dependent relationship between urinary chromium and creatinine excretion. The results can be summarized as 1) there was no significant difference between the observed 24 hr chromium excretion and 24 hr excretion calculated from the one 4 hr samples, 2) a diurnal variation was observed when urinary excretion was expressed as chromium per minute, but no time-related variation could be established when chromium/creatinine (Cr/Cre) ratios in samples from three different periods of the same day were compared, although a significant positive correlation existed between urinary chromium and creatinine concentration, 3) the Cr/Cre ratio was found to be age-dependent, 4) in malnourished children the Cr/Cre ratio was very high and significantly different from that of normal infants, 5) This ratio for the eight diabetics was found to be significantly higher when compared with normal adults. On the basis of these results, it is suggested that morning 4 hr urinary chromium reflects the daily chromium excretion and that the Cr/Cre ratio of single urine samples obtained during this period is a reliable criterion in the evaluation of chromium nutrition of individuals in different conditions, provided that the influence of age is taken into consideration.

Adolescent↗

Changes in iodine excretion in 50-69-y-old denizens of an Arctic society in transition and iodine excretion as a biomarker of the frequency of consumption of traditional Inuit foods.

BACKGROUND: Iodine intake in Greenland has been hypothesized to exceed 10 times the recommended amount. The transition from a traditional Arctic society may change the iodine intake, but no field studies have been performed. OBJECTIVE: We aimed to ascertain iodine intakes, factors affecting iodine intake in circumpolar populations, and the usefulness of urinary iodine excretion as a biomarker for validation of Inuit food-frequency questionnaires. DESIGN: Data were collected in a cohort study of 4 Greenland population groups: Inuit living in the capital city, the major town, and settlements in East Greenland and non-Inuit. Supplement use and lifestyle factors were evaluated with questionnaires, and dietary habits were ascertained with a food-frequency questionnaire. Iodine was measured in spot urine samples. RESULTS: One percent of the population of Greenland was invited, and the participation rate was 95%. Less than 5% of Inuit but 55% of non-Inuit had urinary iodine excretion < 50 microg/24 h. Median urinary iodine excretion declined with the degree of decrease in the traditional lifestyle: it was 198, 195, 147, and 58 microg/24 h among Inuit in settlements, town, and city and in non-Inuit, respectively (P < 0.001). Participants were divided into diet groups calculated from Inuit food frequency. Iodine excretion decreased with increasing intake of imported foods (P < 0.001). In regression models, type of diet and the subject's lifestyle, sex, weight, ethnicity, and intake of iodine-containing supplements affected urinary iodine excretion. CONCLUSIONS: Circumpolar non-Inuit are at risk of iodine deficiency. Departure from the traditional Inuit diet lowers iodine intake, which should be monitored in Arctic societies. Urinary iodine excretion may be a useful biomarker of traditional Inuit food frequency.

Aged↗

Postoperative elevated cortisol excretion is not associated with suppression of 6-sulfatoxymelatonin excretion.

This study tests the hypothesis that elevated postoperative excretion of cortisol is associated with suppression of the nocturnal excretion of 6-sulfatoxymelatonin, the chief metabolite of the circadian hormone, melatonin. Postoperative patients demonstrate circadian rhythm disturbances and suppression of nocturnal melatonin plasma concentration. Since the nocturnal surge in melatonin concentration in normal volunteers is time-locked to the circadian nadir of cortisol concentration, perhaps the attenuation of the nocturnal melatonin surge in postoperative patients results from prolonged elevation in the plasma cortisol concentration. In this observational study performed in 21 patients having unilateral hip or knee arthroplasty, urine was collected every 4 h for the first 48 h after surgery for measurement of urinary 6-sulfatoxymelatonin (EIA) and free cortisol (RIA) excretion. The total (P < 0.05) and peak (P < 0.02) nocturnal 6-sulfatoxymelatonin excretions were lower on the first than the second postoperative night. The nocturnal cortisol nadir preceded the 6-sulfatoxymelatonin surge in 20% of the subjects on night 1 and in 75% of the subjects on night 2. The lack of a consistent relationship between the magnitude or timing of cortisol excretion and 6-sulfatoxymelatonin excretion suggests that cortisol does not mediate postoperative 6-sulfatoxymelatonin suppression.

Adult↗

Influence of hypernatraemia and urea excretion on the ability to excrete a maximally hypertonic urine in the rat.

Rats normally excrete 20-25 mmol of sodium (Na+) + potassium (K+) per kilogram per day. To minimize the need for a large water intake, they must excrete urine with a very high electrolyte concentration (tonicity). Our objective was to evaluate two potential factors that could influence the maximum urine tonicity, hypernatraemia and the rate of urea excretion. Balance studies were carried out in vasopressin-treated rats fed a low-electrolyte diet. In the first series, the drinking solution contained an equivalent sodium chloride (NaCl) load at 150 or 600 mmol l(-1). In the second series, the maximum urine tonicity was evaluated in rats consuming 600 mmol l(-1) NaCl with an 8-fold range of urea excretion. Hypernatraemia (148 +/- 1 mmol l(-1)) developed in all rats that drank 600 mmol l(-1) saline. Although the rate of Na+ + K+ excretion was similar in both saline groups, the maximum urine total cation concentration was significantly higher in the hypernatraemic group (731 +/- 31 vs. 412 +/- 37 mmol l(-1)). Only when the rate of excretion of urea was very low, was there a further increase in the maximum urine total cation concentration (1099 +/- 118 mmol l(-1)). Thus hypernatraemia was the most important factor associated with a higher urine tonicity.

Animals↗