Solute-free Water Reabsorption Research Articles

SGLT2 inhibitor and loop diuretic induce different vasopressin and fluid homeostatic responses in nondiabetic rats.

Loop diuretics are commonly used diuretics in the treatment of fluid retention but induce hypovolemia-related renal dysfunction. Na+-glucose cotransporter 2 (SGLT2) inhibitors induce osmotic diuresis, but body fluid volume is maintained by stimulating vasopressin-induced fluid intake and collecting duct water reabsorption as previously reported in diabetic rats. We aimed to test the hypothesis that unlike SGLT2 inhibitors, loop diuretics lack activation of similar fluid homeostatic mechanisms. Nondiabetic male Sprague-Dawley rats were treated daily by oral gavage with vehicle, the SGLT2 inhibitor ipragliflozin (5 mg/kg), or the loop diuretic furosemide (50 mg/kg) and monitored in metabolic cages for 2 or 7 days. Ipragliflozin and furosemide similarly increased urine volume on day 2. This was associated with increased serum Na+ concentration, urine vasopressin excretion, fluid intake, and solute-free water reabsorption in response to ipragliflozin but not to furosemide. Ipragliflozin maintained fluid balance (fluid intake - urine volume) on day 2 and total body water measured by bioimpedance spectroscopy and serum creatinine on day 7. In comparison, furosemide decreased fluid balance on day 2 and decreased total body water and increased serum creatinine on day 7. Furosemide, but not ipragliflozin, increased plasma renin activity, and systolic blood pressure was similar among the groups. In conclusion, the osmotic diuresis of the SGLT2 inhibitor increased serum Na+ concentration and the vasopressin-related stimulation of fluid intake and renal water retention maintained fluid balance, whereas the loop diuretic did not engage the compensatory vasopressin system. The data suggest differences in vasopressin and fluid homeostatic responses between SGLT2 inhibitors and loop diuretics.NEW & NOTEWORTHY In nondiabetic rats, the Na+-glucose cotransporter 2 (SGLT2) inhibitor ipragliflozin increased vasopressin-related stimulation of fluid intake and free water reabsorption and maintained fluid balance and serum creatinine, whereas the loop diuretic furosemide reduced vasopressin and induced a negative fluid balance followed by a subsequent increase in serum creatinine. This study suggests that differences in vasopressin secretion in response to a SGLT2 inhibitor or loop diuretic may contribute to differences in body fluid status and subsequent renal function.

The Mechanism of the Solute-Free Water Reabsorption Increase in the Rat Kidney by Oxytocin Saluresis

We found an experimental solution to the paradox when the reabsorption of solute-free water increases with a simultaneous increase in diuresis and saluresis in the rat kidney under the oxytocin action. Injection of oxytocin to rats (0.25 nmol/100 g of body weight) increases diuresis from 0.16 ± 0.03 to 0.26 ± 0.02 mL/h, the excretion of solutes from 134 ± 13.7 to 300 ± 16.3 μOsm/h, and the reabsorption of solute-free water, which correlates with the renal excretion of oxytocin (p < 0.001). The mechanism of the effect is that oxytocin decreases the reabsorption of ultrafiltrate in the proximal tubule (the clearance of lithium increases) and increases the fluid flow through the distal segment of the nephron. In vivarium rats, urine osmolality (1010 ± 137 mOsm/kg H2O) and the concentration of vasopressin are high, this causes an increase in the reabsorption of solute-free water. Thus, oxytocin increases saluresis, which, against the background of a high level of endogenous vasopressin, increases the water reabsorption in the collecting ducts.

Osmotic diuresis by SGLT2 inhibition stimulates vasopressin-induced water reabsorption to maintain body fluid volume.

Most of the filtered glucose is reabsorbed in the early proximal tubule by the sodium‐glucose cotransporter SGLT2. The glycosuric effect of the SGLT2 inhibitor ipragliflozin is linked to a diuretic and natriuretic effect that activates compensatory increases in fluid and food intake to stabilize body fluid volume (BFV). However, the compensatory mechanisms that are activated on the level of renal tubules remain unclear. Type 2 diabetic Goto‐Kakizaki (GK) rats were treated with vehicle or 0.01% (in diet) ipragliflozin with free access to fluid and food. After 8 weeks, GK rats were placed in metabolic cages for 24‐hr. Ipragliflozin decreased body weight, serum glucose and systolic blood pressure, and increased fluid and food intake, urinary glucose and Na+ excretion, urine volume, and renal osmolar clearance, as well as urine vasopressin and solute‐free water reabsorption (TcH2O). BFV, measured by bioimpedance spectroscopy, and fluid balance were similar among the two groups. Urine vasopressin in ipragliflozin‐treated rats was negatively and positively associated with fluid balance and TcH2O, respectively. Ipragliflozin increased the renal membrane protein expression of SGLT2, aquaporin (AQP) 2 phosphorylated at Ser269 and vasopressin V2 receptor. The expression of SGLT1, GLUT2, AQP1, and AQP2 was similar between the groups. In conclusion, the SGLT2 inhibitor ipragliflozin induced a sustained glucosuria, diuresis, and natriuresis, with compensatory increases in fluid intake and vasopressin‐induced TcH2O in proportion to the reduced fluid balance to maintain BFV. These results indicate that the osmotic diuresis induced by SGLT2 inhibition stimulates compensatory fluid intake and renal water reabsorption to maintain BFV.

Subtypes of Neurohypophyseal Nonapeptide Receptors and Their Functions in Rat Kidneys.

The nonapeptides of neurohypophysis, vasotocin and mesotocin, detected in most vertebrates, are replaced by vasopressin and oxytocin in mammals. Using bioinformatics methods, we determined the spectrum of receptor subtypes for these hormones in mammals and their physiological effects in the kidneys of rats. A search for sequences similar to the vertebrate vasotocin receptor by proteomes and transcriptomas of nine mammalian species and the rat genome revealed three subtypes of vasopressin receptors (V1a, V1b, and V2) and one type of oxytocin receptors. In the kidneys of non-anesthetized rats, which received a water load of 2 ml per 100 g of body weight, three effects of vasopressin were revealed: 1) increased reabsorption of water and sodium, 2) increased excretion of potassium ions, and 3) increased excretion of sodium ions. It has been suggested that each of the effects on the kidney is associated with selective stimulation of the vasopressin receptor subtypes V2, V1b, and V1a depending on the concentration of nonapeptide. In experiments on non-anaesthetized rats with a water load, the injection of oxytocin reduces the reabsorption of solute-free water in the kidneys and increases the excretion of sodium ions. The possible physiological mechanisms behind the realization of both effects with the participation of a single type of oxytocin receptors are being analyzed. Thus, the spectrum of activated receptor subtypes varies depending on the current concentration of neurohypophyseal hormones, as a result of which the predominant effect on renal function changes, which ensures precise regulation of water-salt homeostasis.

Effect of the Glucagon-like Peptide-1 Mimetic on Ion- and Osmoregulating Renal Functions in Normoglycemia and Hyperglycemia

Incretins are hormones with a wide range of biological activity. We studied the ratio of the glycemic effect of the glucagon-like peptide-1 mimetic and its effect on the renal excretion of sodium and water. It was found that both effects depend on the initial blood concentration of glucose. In normoglycemia, exenatide had no effect on blood sugar level, but it significantly increased urinary sodium excretion and reabsorption of solute-free water. In hyperglycemia the blood glucose concentration was normalized by exenatide, while the excretion of sodium by the kidneys and the reabsorption of solute-free water were increased to a small extent. This pattern was found both in patients with type 2 diabetes mellitus and in rats with hyperglycemia induced by intraperitoneal injection of glucose.

Влияние ингибитора дипептидилпептидазы-4 на выведение ионов натрия и воды почками у крыс при изменениях водно-солевого баланса

Желудочно-кишечный тракт секретирует широкий спектр пептидов, регулирующих метаболические процессы и влияющих на функции почек и водно-солевой баланс. Эффекты данных биологически активных веществ можно усилить увеличением их периода полужизни путем угнетения фермента дипептидилпептидазы-4. Цель исследования - изучение экскреции ионов натрия и воды при угнетении дипептидилпептидазы-4 вилдаглиптином у крыс с различным состоянием водно-солевого баланса. Методика. Состояния гипернатриемии, гиперосмии или гипоосмии моделировали пероральным введением гипертонического и изотонического растворов NaCl и воды. Результаты. Вилдаглиптин вызвал дозозависимое снижение активности фермента дипептидилпептидазы-4 с максимумом эффекта при дозе 1 мг на 100 г массы тела. Его введение перед гипертонической натриевой нагрузкой увеличивало экскрецию натрия на 56%, усилило реабсорбцию осмотически свободной и свободной от натрия воды. Введение ингибитора дипептидилпептидазы-4 перед изотонической натриевой нагрузкой усиливало экскрецию натрия в той же степени, но не влияло на реабсорбцию воды. Инъекция вилдаглиптина, предваряющая водную нагрузку, вызвала антидиуретическую реакцию почек. Заключение. Блокада дипептидилпептидазы-4 вилдаглиптином способствует выведению из организма избыточного количества натрия и изменению реабсорбции воды в зависимости от концентрации ионов натрия в сыворотке крови, вероятно, за счет увеличения периода циркуляции кишечных регуляторных пептидов, секретирующихся в ответ на пероральные нагрузочные пробы NaCl. Данные процессы ускоряют восстановление водно-солевого гомеостаза в условиях поступления избытка натрия через желудочно-кишечный тракт. The gastrointestinal tract secretes multiple peptides that regulate metabolic processes and influence the kidney function and water-salt balance. The effects of these biologically active substances can be intensified by increasing their half-life through inhibition of the dipeptidyl peptidase-4 (DPP-4) enzyme. The aim of the study was investigation of sodium and water excretion after inhibition of DPP-4 with vildagliptin in rats with different states of the water-salt balance. Methods. The hypernatremic, hyperosmotic and hypoosmotic states were modeled by oral administration of hypertonic and isotonic NaCl solutions or water. Results. Vildagliptin induced a dose-dependent decrease in the DPP-4 activity with a maximum effect of 1 mg per 100 g of body weight. Vildagliptin administration prior to the hypertonic sodium load increased sodium excretion by 56% and stimulated reabsorption of solute-free and sodium-free water. Administration of the DPP-4 inhibitor before the isotonic sodium load increased sodium excretion to the same degree without affecting the water reabsorption. A vildagliptin injection prior to the water load resulted in an antidiuretic response of the kidneys. Conclusion. The inhibition of DPP-4 activity with vildagliptin promoted removal of excessive sodium from the body and changed the water reabsorption depending on the sodium concentration in the blood serum, presumably by prolonging circulation of the intestinal regulatory peptides secreted in response to oral NaCl load tests. These processes accelerate restoration of the water-salt homeostasis in the conditions of excessive sodium delivery through the gastrointestinal tract.

Time course effects of methotrexate on renal handling of water and electrolytes in rats. Role of aquaporin-2 and Na-K-2Cl-cotransporter

Methotrexate (MTX) is a derivate of folic acid, commonly used as an anchor drug for the treatment and management of malignant diseases and autoimmune disorders. However, nephrotoxicity is an important drawback of MTX therapy. Unfortunately, there are not enough studies reporting the nature of the renal failure induced by MTX. Thus, the aim of this study was to evaluate the time course of renal handling of water and electrolytes in male Wistar rats, after the exposure to a unique dose of MTX (80 mg/kg b.w.). Experiments were carried out at day 2, day 4, day 8 and day 14 after MTX administration. Several parameters of kidney function related to water and electrolytes handling were evaluated. Renal expression and urinary excretion of aquaporin-2 (AQP2) and Na-K-2Cl-cotransporter (NKCC2) were determined by Western blotting. MTX produced alterations on water handling on the second day after treatment, showing a significant increase in solute free water reabsorption which might be mediated by the increased expression of AQP2 in apical membranes. On the other hand, MTX produced alterations on electrolytes handling on the fourth day after treatment, showing a significant decrease of sodium chloride excretion, mediated at least in part, by the increase renal expression of NKCC2. These results provide valuable information to clinical practice in order to be able to find therapeutic targets that diminish adverse effects and health deterioration. Moreover, MTX treatment altered AQP2 and NKCC2 urinary excretion allowing postulating these transporters as potential biomarkers of MTX induced nephrotoxicity.

Correlation between Urinary Excretion of Arginine-Vasopressin and Renal Reabsorption of Sodium and Water.

We developed an approach for quantitative assay of injected vasopressin in urine samples by ELISA under conditions of physiological suppression of hormone secretion from the neurohypophysis into the blood. In experiments on unanesthetized rats, water load (5 ml/100 g body weight) almost completely blocked secretion of arginine-vasopressin. Injection of arginine-vasopressin in a dose of 0.1 nmol/100 g body weight after water load enhanced reabsorption of solute-free water and renal excretion of Na+, K+, and Mg2+ by 13.3, 5.5, and 5.0 times, respectively; urinary excretion of Ca2+ remained unchanged. It was found that urinary excretion of arginine-vasopressin directly correlated with reabsorption of solute-free water and renal sodium excretion.

Differences between Arginine-Vasotocin and Arginine-Vasopressin Effects on the Rat Kidney in Evolution of Osmoregulation in Vertebrates

Arginine-vasotocin (AVT) is a hormone common to most vertebrates except mammals where it is replaced by vasopressin. A study of the effect of both nonapeptides of the vasopressin family [AVT and arginine-vasopressin (AVP)] showed that in the rat kidney they are involved in the regulation of renal sodium and solute-free water reabsorption. These effects are mediated by different subtypes of V-receptors activated by different blood serum concentrations of the hormone. An immunoenzyme assay (ELISA) was proposed to determine AVT concentrations under almost complete inhibition of AVP secretion. When both hormones were administered at equal doses, AVT broke down slower and acted longer than AVP. A high metabolic rate of the nonapeptide in the blood is supposed to be an evolutionary advantage as a tool to upgrade the water-salt balance regulation. The importance of comparing the effects of hormones lost during the evolution of vertebrates as a method to study the evolution of functions is discussed.

Effects of Selective Agonists of V1a, V2, and V1b Receptors on Sodium Transport in Rat Kidney.

The role of subtypes of vasopressin receptors in modulation of renal sodium reabsorption was studied in in vivo experiments on Wistar rats. Selective V1a receptor agonist reduced sodium reabsorption in the kidneys and expression of these receptors increased by practically 100 times. This effect was similar to the effect of furosemide. Selective V2 receptor agonist enhanced sodium reabsorption in the kidney and simultaneously increased reabsorption of solute-free water. Stimulation of V1b receptors did not affect sodium transport. Our findings attest to the key role of V1a receptors in the regulation of renal excretion of sodium ions.

Effect of oleamide on water and sodium ion transport in osmoregulatory organs of vertebrates

In the frog Rana temporaria L., oleamide solution (10 μmole/L) applied to the isolated basal surface of the skin augmented the short-circuit current (SCC) from 59.8 ± 2.5 to 78.2 ± 1.4 μA/cm2. When applied to the serous membrane of the urinary bladder, oleamide (1 μmole/L) induced more than a 30-fold increase in osmotic water permeability. The addition of argininevasotocin against the background of oleamide further increased SCC across the skin and osmotic water permeability in the bladder. In Wistar rats, intraperitoneal injection of oleamide (0.1 μmole/L per 100 g of body weight) to non-anesthetized animals after water load reduced diuresis by 22% and increased solute-free water reabsorption and urinary sodium excretion by 31% and 55%, respectively, but did not affect urinary potassium excretion. These findings provide evidence of the similarity between the effects of oleamide and nonapeptide neurohypophyseal hormones on water and ion transport in epithelial cells of osmoregulatory organs in vertebrates.

Lessons of pediatrics to physiologist and physiology to pediatrician

The results of joint studies and approaches to solve difficult problems of pathogenesis and treatment of patients in the departments of nephrology and pulmonology were analyzed. The studies have been done over 40 years in common by workers of Pediatric University and Sechenov Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences. The paper is focused on the discussion of choice motivation of research issue and approaches of treatment based on fundamental investigations. The paradoxical phenomenon is revealed - in patients with nocturnal enuresis diuresis increased simultaneously with the rise of solute free water reabsorption. The essence of this phenomenon is established, the use of desmopressin or diclofenac in dependence of disease form ensured treatment of nocturnal enuresis. Green fluorescent protein is applied for study of absorption of native proteins in the intestine, the role of kidneys in protein metabolism and in redistribution of the amino acids in the body was shown. The efficacy of diuretics during the development of renal function is ascertained in children of different age; the cause of renal refractoriness to furosemide in patients with chronic renal failure is established. Measuring the ratio of furosemide/sodium excretion in patients with chronic renal failure showed that the reduction in diuretic delivery to site of action but not the defect of Na,K,2Cl-cotransporter underlay the lower renal response to the same dose of the drug. The effective treatment based on increase in furosemide delivery to thick ascending limb of Henle loop is developed. The new nonapeptide analogue is synthesized; its natriuretic effect is 50 000-fold greater than action of furosemide. The clinical significance of inadequate antidiuretic state in children with severe pneumonia is shown. As a result of these studies, graduates of Pediatric University L. P. Peresheina, L. N. Kosheleva, E. A. Zhukovskaya, V. V. Archipov, A. A. Kuznetsova, A.A. Kanashkina, A. S. Marina, M. V. Burmakin and others defended theses.

Renal function in hepatosplenic schistosomiasis--an assessment of renal tubular disorders.

BackgroundRenal involvement in Schistosoma mansoni infection is not well studied. The aim of this study is to investigate the occurrence of renal abnormalities in patients with hepatosplenic schistosomiasis (HSS), especially renal tubular disorders.MethodsThis is a cross-sectional study with 20 consecutive patients with HSS followed in a medical center in Maceió, Alagoas, Brazil. Urinary acidification and concentration tests were performed using calcium chloride (CaCl2) after a 12-h period of water and food deprivation. The biomarker monocyte chemoattractant protein 1 (MCP-1) was quantified in urine. Fractional excretion of sodium (FENa+), transtubular potassium gradient (TTKG) and solute-free water reabsorption (TcH2O) were calculated. The HSS group was compared to a group of 17 healthy volunteers.ResultsPatients' mean age and gender were similar to controls. Urinary acidification deficit was found in 45% of HSS patients. Urinary osmolality was significantly lower in HSS patients (588±112 vs. 764±165 mOsm/kg, p = 0,001) after a 12-h period of water deprivation. TcH2O was lower in HSS patients (0.72±0.5 vs. 1.1±0.3, p = 0.04). Urinary concentration deficit was found in 85% of HSS patients. The values of MCP-1 were higher in HSS group than in control group (122±134 vs. 40±28 pg/mg-Cr, p = 0.01) and positively correlated with the values of microalbuminuria and proteinuria.ConclusionsHSS is associated with important kidney dysfunction. The main abnormalities found were urinary concentrating ability and incomplete distal acidification defect, demonstrating the occurrence of tubular dysfunction. There was also an increase in urinary MCP-1, which appears to be a more sensitive marker of renal damage than urinary albumin excretion rate.

Puberty alters renal water handling

We investigated the influence of sex and puberty stage on circadian urine production and levels of antidiuretic hormone [arginine vasopressin (AVP)] in healthy children. Thirty-nine volunteers (9 prepuberty boys, 10 prepuberty girls, 10 midpuberty boys, and 10 midpuberty girls) were included. All participants underwent a 24-h circadian inpatient study under standardized conditions regarding Na(+) and fluid intake. Blood samples were drawn every 4 h for measurements of plasma AVP, serum 17-β-estradiol, and testosterone, and urine was fractionally collected for measurements of electrolytes, aquaporin (AQP)2, and PGE2. We found a marked nighttime decrease in diuresis (from 1.69 ± 0.08 to 0.86 ± 0.06 ml·kg(-1)·h(-1), P < 0.001) caused by a significant nighttime increase in solute-free water reabsorption (TcH2O; day-to-night ratio: 0.64 ± 0.07, P < 0.001) concurrent with a significant decrease in osmotic excretion (day-to-night ratio: 1.23 ± 0.06, P < 0.001). Plasma AVP expressed a circadian rhythm (P < 0.01) with a nighttime increase and peak levels at midnight (0.49 ± 0.05 pg/ml). The circadian plasma AVP rhythm was not influenced by sex (P = 0.56) or puberty stage (P = 0.73). There was significantly higher nighttime TcH2O in prepuberty children. This concurred with increased nighttime urinary AQP2 excretion in prepuberty children. Urinary PGE2 exhibited a circadian rhythm independent of sex or puberty stage. Levels of serum 17β-estradiol and testosterone were as expected for sex and puberty stage, and no effect on the AVP-AQP2-TcH2O axis was observed. This study found a circadian rhythm of plasma AVP independent of sex and puberty stage, although nighttime TcH2O was higher and AQP2 excretion was more pronounced in prepuberty children, suggesting higher prepuberty renal AVP sensitivity.

Renal Tubular Dysfunction in Sickle Cell Disease

Background/Aims: Kidney abnormalities are one of the main chronic complications of sickle cell disease (SCD). The aim of this study is to investigate the occurrence of renal tubular abnormalities among patients with SCD. Methods: This is a prospective study with 26 SCD adult patients in Brazil. Urinary acidification and concentration tests were performed using calcium chloride (CaCl₂), after a 12h period of water and food deprivation. Fractional excretion of sodium (FE_Na), transtubular potassium gradient (TTKG) and solute free water reabsorption (TcH₂O) were calculated. The SCD group was compared to a group of 15 healthy volunteers (control group). Results: Patient`s average age and gender were similar to controls. Urinary acidification deficit was found in 10 SCD patients (38.4%), who presented urinary pH >5.3 after CaCl₂ test. Urinary osmolality was significantly lower in SCD patients (355±60 vs. 818±202mOsm/kg, p=0.0001, after 12h period water deprivation). Urinary concentration deficit was found in all SCD patients (100%). FE_Na was higher among SCD patients (0.75±0.3 vs. 0.55±0.2%, p=0.02). The TTKG was higher in SCD patients (5.5±2.5 vs. 3.0±1.5, p=0.001), and TcH₂O was lower (0.22±0.3 vs. 1.1±0.3L/day, p=0.0001). Conclusions: SCD is associated with important kidney dysfunction. The main abnormalities found were urinary concentrating and incomplete distal acidification defect. There was also an increase in the potassium transport and decrease in water reabsorption, evidencing the occurrence of distal tubular dysfunction.

Temporal delays and individual variation in antidiuretic response to desmopressin

This study aimed to estimate the relationship between pharmacokinetics and the antidiuretic effect of desmopressin. In the investigator-blind, randomized, parallel group study, 5 dose groups and 1 placebo group, each consisting of 12 healthy, overhydrated, nonsmoking male subjects 18-55 yr of age were infused intravenously over 2 h with placebo or 30, 60, 125, 250, and 500 ng desmopressin in 50 ml of normal saline. Plasma desmopressin and urine osmolality rose by variable amounts during the infusions of 60, 125, 250, and 500 ng desmopressin. Plotting mean urine osmolality against the concurrent mean plasma desmopressin yielded a temporal delay between pharmacokinetic (PK) and -dynamic (PD) responses in all dose groups. Using simulation from the indirect-response model, assuming a constant (4 ng/ml) desmopressin concentration, this delay between PK and PD was estimated at 4 h (10th-90th percentile: 1.8-8.1). Within each group, however, there were large individual variations (2- to 10-fold) in the magnitude and duration of the antidiuretic effect. The antidiuretic effect of intravenous desmopressin in water-loaded healthy adults varies considerably due largely to factors other than individual differences in pharmacokinetics. The antidiuretic effect is time as well as dose dependent and may be self-amplifying. The most likely explanation for these findings is that the time required for a given level of plasma desmopressin to exert its maximum antidiuretic effect varies markedly from person to person due to individual differences in the kinetics of one or more of the intracellular mechanisms that promote the reabsorption of solute-free water by principal cells in renal collecting tubules.

Correlation of renal solute-free water reabsorption and energy of interaction of vasotocin analogs with V2 receptor

The nonapeptide-receptor interaction energy calculated from docking algorithms was compared with the effect of the same peptides upon solute-free water reabsorption in rat kidney in vivo. Vasotocin and some of its analogs were injected intramuscularly into conscious female Wistar rats in doses from 0.1 pmol to 0.5 nmol/kg of body weight after oral water load (50 ml/kg of body weight). A significant correlation was found between the calculated energy of peptide interaction with V2 receptors and an increase in the renal solute-free water reabsorption stimulated by injection of nonapeptides. The results evidence that physiological changes in rat kidney in vivo induced by vasotocin analogs can be accurately simulated by virtual modeling of their interactions with V2 receptors.

Sleep deprivation induces excess diuresis and natriuresis in healthy children

Urine production is reduced at night, allowing undisturbed sleep. This study was undertaken to show the effect of sleep deprivation (SD) on urine production in healthy children. Special focus was on gender and children at an age where enuresis is still prominent. Twenty healthy children (10 girls) underwent two 24-h studies, randomly assigned to either sleep or SD on the first study night. Diet and fluid intake were standardized. Blood samples were drawn every 4 h during daytime and every 2 h at night. Urine was fractionally collected. Blood pressure and heart rate were noninvasively monitored. Blood was analyzed for plasma antidiuretic hormone (AVP), atrial natriuretic peptide (ANP), angiotensin II, aldosterone, and renin. Urine was analyzed for aquaporin-2 and PGE(2). Successful SD was achieved in all participants with a minimum of 4 h 50 min, and full-night SD was obtained in 50% of the participants. During SD, both boys and girls produced markedly larger amounts of urine than during normal sleep (477 ± 145 vs. 291 ± 86 ml, P < 0.01). SD increased urinary excretion of sodium (0.17 ± 0.05 vs. 0.10 ± 0.03 mmol·kg(-1)·h(-1)) whereas solute-free water reabsorption remained unchanged. SD induced a significant fall in nighttime plasma AVP (P < 0.01), renin (P < 0.05), angiotensin II (P < 0.001), and aldosterone (P < 0.05) whereas plasma ANP levels remained uninfluenced (P = 0.807). Nighttime blood pressure and heart rate were significantly higher during SD (mean arterial pressure: 78.5 ± 8.0 vs. 74.7 ± 8.7 mmHg, P < 0.001). SD leads to natriuresis and excess diuresis in healthy children. The underlying mechanism could be a reduced nighttime dip in blood pressure and a decrease in renin-angiotensin-aldosterone system levels during sleep deprivation.

Effect ofCuscuta chinensison Renal Function in Ischemia/Reperfusion-Induced Acute Renal Failure Rats

The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

Mechanism of 1-deamino-arginine vasotocin induced natriuresis in rats

1-Deamino-arginine vasotocin (1dAVT) induced diuresis and a considerable increase in urinary sodium excretion in female Wistar rats. Sodium fractional excretion rose up to 19.3±1.1%. An increase in urine flow rate after 1dAVT (0.5nmol/kg body-weight [bw]) injection was accompanied by a significant rise of the solute-free water reabsorption. The 1dAVT-induced natriuresis was as high as natriuresis produced by injection of a maximal dose of furosemide (10mg/kgbw). V1-receptor antagonists (ОРС-21268, [β-mercapto-β,β-cyclopentamethylenepropionyl1,O-Me-Tyr2,Arg8]-vasopressin) blocked the increase in urinary sodium excretion after the 1dAVT injection. The 1dAVT-induced natriuresis was strongly correlated with an increase in the urinary cGMP and prostaglandin E2 excretion. The natriuretic effect of 1dAVT did not depend on the formation of nitric oxide (NO) or atrial natriuretic peptide of which concentration in the rat blood serum remained stable. The above results indicate that the 1dAVT has unique effects on rat kidney compared to all other known diuretics – it induces extremely high natriuresis and stimulates solute-free water reabsorption. Mechanism of the natriuretic effect of 1dAVT includes decrease in tubular sodium reabsorption due to activation of V1-like receptors and formation of cGMP and PGЕ2.