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Urolithiasis is a common multifactorial disease characterized by a high recurrence rate. This review is devoted to the urine pH as one of the main factors determining its lithogenic properties. It affects the excretion of lithogenic substances and stone formation inhibitors, the solubility, and the crystallization of substances involved in stone formation. The urine pH significantly affects the solubility of uric acid in urine, which decreases at a pH < 5.5. This explains the high incidence of uric acid concretions in patients with metabolic syndrome. Their insulin resistance leads to a decrease in the excretion of ammonium ions in the proximal tubules, leading to persistent urine acidification. The activity of many transport processes involved in the processing of calcium, citrates and phosphates is sensitive to changes in systemic or local pH. The data on the effect of urine pH on the solubility of calcium oxalate remain contradictory. At the same time, there is no doubt about the determining role of urine pH in the excretion of citrate, the most important stone formation inhibitor. The alkaline urine pH promotes the formation of concretions containing calcium phosphates. In conditions of constantly elevated urine pH in patients with persistent urease-producing urinary tract infection, a rapid growth of "infectious" concretions occurs. The review summarizes information on the causes of the decrease and increase in the urine pH, as well as the possibilities of medicinal and non-medicinal methods of modifying the urine pH during the prevention of stone formation recurrence.

Glucagon-like peptide-1 (GLP-1), a product of partial proteolysis of proglucagon, is involved not only in regulation of carbohydrates, but also in water-salt metabolism. The study examined the role of proglucagon derivatives GLP-1, GLP-2, and oxyntomodulin in rat osmoregulation. Of them, only blood plasma GLP-1 increased in response to water load (20 ml/kg). Administration of glucose (1.5 g/kg) elevated GLP-1 and oxyntomodulin but did not change the level of GLP-2. GLP-1 accelerated excretion of excess water during hyperhydration, whereas GLP-2 decreased this parameter. No physiological effects of oxyntomodulin in the kidneys were revealed. Probably, the blood levels of proglucagon derivatives are independently regulated for each peptide. In contrast to GLP-2 and oxyntomodulin, GLP-1 is involved in osmoregulation.

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.

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.

Glucagon-like peptide-1 (GLP-1), a product of partial proteolysis of proglucagon, is involved not only in regulation of carbohydrates, but also in water-salt metabolism. The study examined the role of proglucagon derivatives GLP-1, GLP-2, and oxyntomodulin in rat osmoregulation. Of them, only blood plasma GLP-1 increased in response to water load (20 ml/kg). Administration of glucose (1.5 g/kg) elevated GLP-1 and oxyntomodulin but did not change the level of GLP-2. GLP-1 accelerated excretion of excess water during hyperhydration, whereas GLP-2 decreased this parameter. No physiological effects of oxyntomodulin in the kidneys were revealed. Probably, the blood levels of proglucagon derivatives are independently regulated for each peptide. In contrast to GLP-2 and oxyntomodulin, GLP-1 is involved in osmoregulation.

An increase of total glucagon-like peptide-1 (GLP-1) concentration in the plasma in rats was revealed 5 min after oral, but not intraperitoneal administration of NaCl or Trizma HCl solutions. The increase in GLP-1 level was similar to that after oral glucose administration. After intraperitoneal administration of 2.5% NaCl, GLP-1 mimetic exenatide accelerated natriuresis and urinary chloride excretion. Under conditions of normonatriemia and hyperchloremia induced by injection of 6.7% Trizma HCl, exenatide stimulated chloride excretion and reabsorption of sodium ions in the kidneys. These findings suggest that GLP-1 participates in selective regulation of the balance of sodium and chloride ions.

The aim of the present study was to compare effects of glucagon-like peptide-1 (GLP-1) mimetic exenatide on glucose and water-salt homeostasis in animals with different level of renal tubular proximal reabsorption - rats (Rattus norvegicus) and frogs (Rana temporaria). Following glucose tolerance test, in rats exenatide promoted rapid recovery of normoglycemia, whereas in frogs delayed this process. In water-loaded rats exenatide essentially augmented solute-free water clearance and enhanced natriuresis in furosemide-treated rats.-In frogs exenatide did not alter urinary flow rate, urinary sodium excretion and solute-free water clearance under water diuresis and furosemide treatment. It is suggested that the invol- vement of GLP- 1 in regulation of water-salt homeostasis in mammals should be preceded by key evoluti- onary transformation - increase in glomerular filtration rate and proximal tubular reabsorption.

The aim of this study was to compare the effects of exenatide, a glucagon-like peptide-1 (GLP-1) mimetic, on glucose and water–salt homeostasis in animals with different levels of renal proximal tubular reabsorption, rats (Rattus norvegicus) and frogs (Rana temporaria). Following the glucose tolerance test, in rats exenatide promoted fast recovery of normoglycemia, whereas in frogs it delayed this process. In water-loaded rats, exenatide augmented solute-free water clearance and enhanced natriuresis in furosemide-treated animals. In frogs, exenatide did not alter the urinary flow rate, urinary sodium excretion and solute-free water clearance under water diuresis and furosemide treatment. It is suggested that the involvement of GLP-1 in regulation of water–salt homeostasis in mammals was preceded by a key evolutionary transformation, the increase in the glomerular filtration rate and proximal tubular reabsorption.

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.

GFP signal intensity revealed similar patterns of GFP absorption in rat and frog proximal tubular cells depending on the amount of the administered protein [1, 3]. At the same time, in frog kidney there were demonstrated some peculiarities of GFP fluorescence distribution associated with a smaller number of nephrons, their intermittent activity and a reduced glomerular filtration under the effect of antidiuretic hormone [2, 3]. Efficiency of the model fluorescent proteins in physiological experiments and a paucity of evidence concerning functional differences between the mammalian metanephros and amphibian mesonephros urged a detailed comparative analysis of protein filtration and absorption in kidneys of rats and frogs. The goal of this investigation was to compare functional parameters of the kidney activity in the above species including the glomerular filtration rate (GFR) and dynamics of GFP and YFP uptake and accumulation by proximal tubular cells during endocytosis. Experiments were carried out on Wistar rat females (Rattus norvegicus) and hibernating brown frog males (Rana temporaria). Highly purified recombinant GFP and YFP were obtained from the Laboratory of protein synthesis mechanisms (Institute of Protein Research RAS, Pushchino, SHORT COMMUNICATIONS

We have found the physiological mechanism of intensification of the excessive fluid removal from the body under the action of glucagon-like peptide-1 and its analog exenatide. Under the water load in rats, exenatide significantly increased the clearance of lithium, reduced fluid reabsorption in the proximal tubule of the nephron and intensified reabsorption of sodium ions in the distal parts, which contributed to the formation of sodium-free water and faster recovery of osmotic homeostasis. Blocking this pathway with a selective antagonist of glucagon-like peptide-1 receptors slowed down the elimination of excessive water from the body.

Blood concentration of glucagon-like peptide-1 (GLP-1) increased 5 min after per os administration of water, sodium chloride solution, or glucose solution. Changes in blood osmolality or blood glucose level did not stimulate GLP-1 release. A method of short-term increase in the gastric capacity in rats using an inflating balloon attached to the Foley catheter was developed in order to test the hypothesis that excitation of the upper gastrointestinal tract receptors is a primary signal for the GLP-1 secretion during oral intake of the substances. Mechanical gastric distension in rats caused elevation of the blood GLP-1 concentration which was comparable to the effects of oral administration of water, sodium chloride, and glucose solutions.

The effects of vertebrate neurohypophysial nonapeptides (vasopressin, vasotocin and their synthesized analogs) on urinary magnesium excretion were studied in rats. Neurohypophysial hormones and their analogs at doses stimulating V2-receptors (0.0001–0.001 nmol/100 g BM) exerted antidiuretic effect and reduced urinary magnesium excretion. At higher doses, activating V2 and V1a-receptors (0.025–0.1 nmol/100 g BW), vasotocin and its analogs (deamino-vasotocin (dAVT), deamino-Thr4-vasotocin, deamino-hArg8-vasotocin, deamino-monocarbo-vasotocin) enhanced excretion of magnesium and sodium ions. A direct relationship was revealed between the enhanced renal excretion of sodium and magnesium ions under these conditions. After the V1a-receptor antagonist injection, dAVT caused a 10-fold lower increase in magnesium excretion. The V2-receptor antagonist did not affect dAVT-induced magniuresis. The data obtained suggest that V-receptors are involved in magnesium transport regulation in the rat kidney.

Sodium balance in the body determines the key physiological parameters, such as the volume of extra� cellular fluid and its osmolality. Blood volume affects hemodynamics and blood content of the vessels, and blood plasma osmolality determines the volume of each cell in the body. Despite changes in the supply of Na + salts and the rate of salt excretion by kidneys, intestine and other organs, the Na + balance in humans and mammalians is continuously maintained at a sta� ble level, and it is controlled by the nervous system and endocrine glands. Physiologically active substances affecting Na + excretion by the kidney include aldos� terone (1), atriopeptid (2, 3), prostaglandin Е2 (4-6), etc. We recently demonstrated that incretin, a peptide of the gastrointestinal tract (glucagonlike peptide�1), produced in response to food intake (7), is involved in the regulation of excretion of Na + and free water by the kidney (8-10). The goal of this study was to deter� mine the role of incretins in Na + balance in the cases of alternative types of impairment of Na + balance (hypoand hypernatremia). Usually, some hormones are secreted upon an increase in the content of Na + in the body, and other hormones are secreted when the content of Na + is decreased. Aldosterone enters the blood during hypo� volemia, which means a sodium deficit (1), the secre� tion of atriopeptide into the bloodstream is observed during hypervolemia (2), and vasopressin is secreted during hypovolemia and hyperosmia (11). Based on the above facts, the goal of the present study was to clarify the role of incretin based on the effect of its mimetic during hypervolemia at an unchanged, a decreased or an increased Na + concen� tration in the blood serum. In other words, against a background of an increased volume of extracellular fluid, we estimated the effect of incretin and reaction of the body to differently directed shift of Na + concen� tration in the blood serum. Exenatide, which is more resistant to enzymatic degradation in the blood com� pared with glucagonlike peptide�1 was used as an incretin mimetic (12). Experiments were carried out on female Wistar rats with body weights of 180-230 g. The rats received standard pelleted food (recipe PK�120, Aller Petfood, Russia) and had free access to water. After 5 p.m. in the previous evening and in the morning of the experi� ment, the rats received no food, but they had access to water. At the end of experiment, the rats were returned to their cages in a vivarium and used in repeated exper� iments no earlier than after one week. Animal han� dling and experiments were performed according to Russian and international regulations for the handling of laboratory animals. During the experiment, the rats were placed to individual cages with wire bottoms through which urine could flow via a funnel into a vol� umetric tube.

Vasopressin and nonmammalian hormone vasotocin are known to increase the water permeability of mammalian collecting ducts, frog skin and the urinary bladder. Neurohypophysial nonapeptides have also been shown to interfere with the regulation of renal ion transport. The subject of this study was a search for vasopressin and vasotocin analogues with selective effects on renal water, sodium and potassium excretion. During this study, we synthesised the following peptides: 13 vasotocin analogues modified at positions 4 (Thr or Arg), 7 (Gly or Leu) and 8 (D-Arg, Lys or Glu); 4 vasopressin analogues modified at positions 4 and 8; and 9 peptides shortened or extended at the C-terminal or with substitutions for Gly-NH2. Most of these peptides had mercaptopropionic acid (Mpa) instead of Cys in position 1. The effects of these nonapeptides on renal water, sodium and potassium transport were evaluated in in vivo experiments using Wistar rats. Some nonapeptides possessed antidiuretic, natriuretic and kaliuretic activities ([Mpa(1)]-arginine vasotocin, [Mpa(1), homoArg(8)]-vasotocin, [Mpa(1), Thr(4)]-arginine vasotocin and [Mpa(1), Arg(4)]-arginine vasopressin). Substitutions at positions 4 and 8 increased the selectivity of peptide actions. The antidiuretic [D-Arg(8)]-vasotocin analogues had no effects on sodium excretion. [Mpa(1), Arg(4)]-arginine vasotocin was antidiuretic and kaliuretic but not natriuretic. [Mpa(1), Glu(8)]-oxytocin had weak natriuretic activity without any effects on water and potassium transport. In accordance with the data obtained, synthesised vasotocin analogues could be good candidates for pharmaceuticals selectively regulating renal sodium and potassium transport, which is of clinical importance.

During the long-term stay in closed environment of the orbital space station, it is extremely important that the light conditions and color scheme were favorable for the working capacity of a cosmonaut. The systems of lighting should ensure visual comfort for the crew members under stressful conditions and, in addition, they should appropriate to their health and recovery of functional reserves during the long-duration flight. To solve this task, the distribution of luminosity and chromaticity within a closed space should be taken into account. For better understanding the perception of visual information, we studied the color space-frequency characteristics of the organ of vision (SFC VO). A set of sensors was used to estimate psychophysiological parameters. After preadaptation of an operator, VO contrast sensitivity was measured by determining the thresholds of advent and disappearance of the test objects; this was accompanied by fixation of the time and adaptive brightness. Analysis of the experimental data made it clear that the color contrast sensitivity and directly related SFC of the organ of vision are valuable markers for interrelationships between processing of visual information and psychophysiological state of a human. Note that the color SFC VO not only illustrates deviations but also enables their quantification. Changes in psychophysiological state are accompanied by the appropriate changes in SFC VO, which should be taken into account in developing the neural information technologies used for health recovery and light-and-color control of environment.

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.

New analogs of exenatide with amino acid substitutions at 14, 35, and 39 have been synthesized. They were shown to be more stable than original exenatide in aqueous solutions. In vivo testing on rat models of glucose loading showed that exenatide and its novel analogs possess hypoglycemic activity and stimulate renal excretion of sodium and magnesium ions and osmotically free water but have virtually no effect on the elimination of potassium ions. Experiments with isolated skin and urinary bladder preparations from male frogs showed that exenatide and its analogs promote biosynthesis of physiologically active compounds modulating renal functions.

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 (0.5 nmol/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/kg bw). V(1)-receptor antagonists (ОРС-21268, [β-mercapto-β,β-cyclopentamethylenepropionyl(1),O-Me-Tyr(2),Arg(8)]-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 E(2) 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 V(1)-like receptors and formation of cGMP and PGЕ(2).

The rate of excretion of the total protein and albumin during an increase in diuresis after water loading was studied in healthy volunteers. In the control period, the excretion of protein (7.3–11.1 mg/2 h) and albumin (0.29–0.42 mg/2 h) was within of the physiological norm range. Water loading (20 ml/kg) caused water diuresis, urine formation rate increased by a factor of 15, and the reabsorption of solute-free water changed into its excretion. The increase in diuresis was accompanied by a statistically significant increase in the urinary protein and albumin excretion, as well as by an increase in the protein-to-creatinine ratio. After water loading, the excretion of total protein, as compared to the initial period, increased by a factor of 8.4, and of the albumin excretion, by a factor of 2.8, exceeding the generally accepted limits of the norm. The role of intraglomerule hemodynamics in the development of physiological proteinuria related to water diuresis is discussed.

Experiments on healthy rats showed that increased diuresis induced by administration of water, polyethylene glycol 400, furosemide, or 1-desamino-arginine-vasotocin is associated with increased protein excretion by the kidneys. The results can be explained by enhanced filtration of plasma proteins in glomeruli during polyuria of various geneses.

Effects of neurohypophysial nonapeptides of vertebrates (vasopressin, vasotocin, and their synthetized analogues) on urinary magnesium excretion were studied in rats. Neurohypophysial hormones and their analogues at doses stimulating V2-receptors (0.0001-0.001 nmol/100 g BW) produced antidiuretic effect and reduced urinary magnesium excretion. At the higher doses activating V2- and V1a-receptors (0.025-0.1 nmol/100g BW), vasotocin and its analogues (deamino-vasotocin (dAVT), deamino-Thr4-vasotocin, deamino-hArg8-vasotocin, deaminomonocarbo-vasotocin) enhanced excretion of magnesium and sodium ions. Direct relation between increase in renal excretion of sodium and magnesium ions was found under these conditions. dAVT induced 10 times lesser increase in magnesium excretion after administration of a V1a-receptor antagonist. An antagonist of V2-receptors did not affect the dAVT-induced magniuresis. The obtained data suggest that V-receptors take part in regulation of magnesium transport in rat kidney.

Experiments on Wistar rats showed that single intraperitoneal injection nonselective NO-synthase inhibitor L-NAME in a dose of 50 mg/kg was followed by transient proteinuria and albuminuria. This effect was not reproduced by injection of ODQ, an inhibitor of intracellular effects of NO, and arginine, but D-NAME, an optical isomer of L-NAME not blocking NO-synthase, produced similar, though less pronounced effect. The degree of proteinuria and albuminuria increased in combined treatment with nitroarginine methyl esters and 1-deamino-arginine vasotocin or arginine vasopressin. Proteinuria during treatment with arginine derivatives attests to not only their effect on the charge of the filtration membrane, but also the participation of NO-dependent processes in the regulation of ultrafiltration in renal glomeruli.

Injection of a glucagon-like peptide-1 mimetic accelerated recovery of the initial status of water-salt balance in rats after water or saline load (2.5% NaCl). This effect is mediated by a decrease in proximal fluid reabsorption and change in ion and water transport in the distal part of renal tubules. We developed a new approach to calculation of additional fluid inflow from the proximal tubule to the distal tubule and distal sodium reabsorption under the influence of this mimetic in rats. The expected values corresponded to experimental results, which confirmed our hypothesis on the physiological mechanism for the involvement of the kidneys in the homeostatic effect of glucagon-like peptide-1 under variations in water-salt balance.

Цель. Разработки метода оценки функции почки по осмотическому концентрированию мочи, которое особенно страдает при ряде форм патологии почки и находит отражение в таких симптомах как гипостенурия и изостенурия. Материалы и методы. Обследовано 29 детей с СД (18 мальчиков и 11 девочек) и 10 практически здоровых подростков (4 мальчика и 6 девочек). Пациенты с СД были разделены на 3 группы: (1) диабетическая нефропатия - 9 детей; (2) больные со стажем диабета более 5 лет без диабетического поражения почек - 11 детей; (3) подростки с небольшой длительностью СД без осложнений - 9 человек. Результаты. Исследование биохимических параметров сыворотки крови у пациентов с СД выявило несколько более высокие значения осмоляльности (289,9 мосмоль/кг Н2О, n=29) по сравнению с группой контроля (282,4 мосмоль/кг Н2О, n=10, p

Solute-free water clearance increased by 186% in water loaded rats treated with glucagon-like peptide 1 compared to untreated group. The effect of glucagon-like peptide 1 was reproduced in experiments with its synthetic analogue exenatide. Serum osmolality in water loaded rats treated with exenatide was closer to normal level on 30, 45, 60 min of experiment compared to the untreated group and reached the control value in 60 min. Administration of glucagon-like peptide 1 receptor antagonist to water loaded rats delayed (5 ml per 100 g bw) or prevented (2 ml per 100 g bw) increase in solute-free water clearance. The obtained data suggest the involvement of glucagon-like peptide 1 in osmotic homeostasis and indicate the unique physiologic role of incretins in regulation of water balance.

The investigation deals with effect of analogues of conopressin S--a peptide of the vasopressin family with amino acid replacement in the 2nd and 4th positions (characteristic of invertebrate peptides)--on transport of water and ions in the rat kidney. At administration to female Wistar rats, 1-deamino-conopressin S produced a weak action on water transport and had no effect on urinary K+ and Na+ excretion. Its analogue, 1-deamino-Tyr2-conopressin S, caused antidiuretic and kaliuretic action without affecting the Na+ excretion. Estimation of significance of the variant of optic isomer of arginine in the 4th and 8th position of the molecular for the antidiuretic and kaliuretic action of the peptide showed that 1-deamino-Tyr2,D-Arg4-conopressin S and 1-deamino-Tyr2,D-Arg4,8-conopressin S did not affect the urinary K+ excretion and renal water reabsorption, whereas action of 1-deamino-Tyr2,D-Arg8-conopressin S did not differ from action of 1-deamino-Tyr2-conopressin S. Thus, it has been established that the selective kaliuretic action of analogues of conopressin S on rat kidney depends on the presence of tyrosine in the 2nd and of L-arginine, but not of D-arginine, in the 4th position of the molecule.

SUMMARY 1. The aim of the present study was to clarify the mechanisms mediating the effect of a glucagon-like peptide-1 (GLP-1) mimetic on solute-free water excretion in rats. 2. The GLP-1 mimetic exenatide (0.05–5.0 nmol/kg, i.m.), alone and in combination with either a vasopressin V2 receptor antagonist (15 nmol/kg, i.p.) or vasopressin (0.01 nmol/kg, i.m.), was injected into control and water-loaded (water 10–50 mL/kg, p.o., or 50 mL/kg of 0.6% NaCl, i.p.) rats to evaluate the role of collecting duct water permeability in the hydrouretic effect. Urinary prostaglandin (PG) E2 excretion and the effects of diclofenac (5 mg/kg, i.m.) and GLP-1 receptor antagonist (0.15 lmol/kg, i.p.) on exenatide action were assessed. 3. The hydrouretic effect of exenatide was equivalent following oral or intraperitoneal water loading, and was proportional to the volume of water administered. Injection of exenatide, under conditions of a maximal decrease in collecting duct water permeability (V2 receptor antagonist administration in waterloaded rats), additionally stimulated solute-free water formation. The GLP-1 receptor antagonist weakened the hydrouretic action of exenatide. Urinary PGE2 excretion increased following water loading (47 � 6 vs 24 � 4 ng/kg over a 30 min period) and was enhanced as a result of additional exenatide injection (69 � 10 ng/kg). Diclofenac and vasopressin delayed the hydrouretic effect of exenatide. 4. The effect of exenatide on solute-free water clearance in water-loaded rats is presumably mediated by stimulation of PGE2 secretion and reinforcement of tubular fluid influx from the proximal tubule to the distal segment of the nephron and collecting duct.

The aim of the present study was an investigation of mechanisms mediating selective effect of vasotocin analogues on water, sodium, and potassium excretion. We tested vasotocin analogues: Mpa 1 -vasotocin (dAVT), Mpa 1 -Arg 4 -vasotocin (dAAVT) and Mpa 1 -DArg 8 -vasotocin (dDAVT). The effects on water, sodium, and potassium transport were evaluated in experiments using normal and water-loaded Wistar rats. It was shown that all tested peptides exerted antidiuretic activity. Vasotocin and dAVT induced natriuresis and kaliuresis in rats. V 1a agonist (Phe 2 -Ile 3 -Orn 8 -vasopressin) reproduced the renal effects of dAVT on sodium and potassium excretion but not on water reabsorption. dAAVT, dDAVT and V 2 agonist (desmopressin) induced kaliuresis without any effect on sodium excretion. Natriuresis was associated with increase in cGMP excretion, whereas kaliuresis was correlated with rise of cAMP excretion. V 1a antagonist (Pmp 1 -Tyr(Me) 2 -vasopressin) significantly reduced the dAVT-stimulated natriuresis and did not influence on urinary potassium excretion. V 2 antagonist (Pmp 1 -DIle 2 -Ile 4 -vasopressin) significantly reduced the dAVT- and dAAVT-induced kaliuresis. It is assumed that effects of the nonapeptides on sodium and potassium transport are independent of their antidiuretic activity and mediated by different subtypes of V receptors (the V 1a or V 1a -like receptor for natriuretic effect and V 2 or V 2 -like one for kaliuretic). In accordance to the data obtained, there is a possibility of selective regulation of renal water reabsorption and urinary sodium and potassium excretion with involvement of neurohypophysial hormones.

Vasopressin and nonmammalian hormone vasotocin are known to increase the water permeability of mammalian collecting ducts, frog skin and the urinary bladder. Neurohypophysial nonapeptides have also been shown to interfere with the regulation of renal ion transport. The subject of this study was a search for vasopressin and vasotocin analogues with selective effects on renal water, sodium and potassium excretion. During this study, we synthesised the following peptides: 13 vasotocin analogues modified at positions 4 (Thr or Arg), 7 (Gly or Leu) and 8 (D-Arg, Lys or Glu); 4 vasopressin analogues modified at positions 4 and 8; and 9 peptides shortened or extended at the C-terminal or with substitutions for Gly-NH2. Most of these peptides had mercaptopropionic acid (Mpa) instead of Cys in position 1. The effects of these nonapeptides on renal water, sodium and potassium transport were evaluated in in vivo experiments using Wistar rats. Some nonapeptides possessed antidiuretic, natriuretic and kaliuretic activities ([Mpa(1)]-arginine vasotocin, [Mpa(1), homoArg(8)]-vasotocin, [Mpa(1), Thr(4)]-arginine vasotocin and [Mpa(1), Arg(4)]-arginine vasopressin). Substitutions at positions 4 and 8 increased the selectivity of peptide actions. The antidiuretic [D-Arg(8)]-vasotocin analogues had no effects on sodium excretion. [Mpa(1), Arg(4)]-arginine vasotocin was antidiuretic and kaliuretic but not natriuretic. [Mpa(1), Glu(8)]-oxytocin had weak natriuretic activity without any effects on water and potassium transport. In accordance with the data obtained, synthesised vasotocin analogues could be good candidates for pharmaceuticals selectively regulating renal sodium and potassium transport, which is of clinical importance.

Experiments on Wistar rats showed that exenatide (0.015–0.5 nmol per 100 g body weight) somewhat increased renal excretion of potassium from 7 ± 1 to 16 ± 1 μmol/h/100 g body weight (p

We compared parameters of water-salt balance in Wistar female rats fed normal chows during more than 2 weeks. Potassium content was 1.4-fold higher in diet I than in diet II, and sodium end water content was 3.3- and 7.5-fold higher in diet II than in diet I. Blood osmolality and concentration of Na+, K+, Mg2+ were equal in rats fed different chow. In water-loaded rats (5 ml of water/100 bw per os) fed different chow, urine flow rate did not differ, but solute-free water excretion was higher by 40.2% in the rats fed diet II vs. diet I. The sort of diet did not affect the renal sodium excretion during oral administration of 5 ml 0.9% NaCl per 100 g bw to rats. After vasopressin injection solute-free water reabsorption was 1.5-fold higher in rats fed diet II. Natriuretic and hydruretic effect of exenatide, glucagon-like peptide 1 mimetic, was weaker in rats fed diet I. The data obtained indicate that organism can effectively maintain blood parameters. The modulation of hormone regulatory effects on water and sodium balance was found to depend on the state of organism under diet consumed continuously.

Exenatide injection to female Wistar rats induced an increase in diuresis, urinary sodium and mild potassium excretion. The maximum natriuretic effect of exenatide was 18500 times more pronounced compared to that of furosemide in equimolar dose. The natriuretic and diuretic effects after combined administration of maximum doses of exenatide and furosemide were additive, which was indicative of different mechanisms of their action on the nephron. Exenatide probably inhibits sodium reabsorption in renal proximal segment. The data obtained might be essential for assessment of the clinical use of exenatide to excrete extracellular fluid excess in cases of edemation and to maintain potassium balance.

Efficacy of drugs reduced proximal reabsorption was compared in experiments with female Wistar rats. Urine flow rate for the 1st h of experiment was enhanced after polyethylene glycol-400 (PEG) and 6% Na2SO4 infusion by over 30-fold, exenatide--40-fold, glycerol--11-fold as compared with the control. The maximal values of Na+ excretion were observed during Na2SO4 and exenatide administration (280 +/- 31 micromol/h vs. 3.2 +/- 0.6 Imol/h/100 g bw). The highest K+ excretion was revealed in experiments with glycerol administration (41 +/- 5 micromol/h vs. 7 +/- 2 micromol/h/100 g bw), Mg2+ --after exenatide injection (5.3 +/- 1.3 micromol/h vs. 0.16 +/- 0.03 micromol/ h/100 g bw). Diuretic effects were additive after combined administration of maximal doses of exenatide and PEG which suggests a different mechanism of action of solutes filtrated (PEG) to the proximal nephron segment and generated due to Na+/HW-exchange inhibition (exenatide). Osmotic diuretics differ by potency, mechanism of diuretic action and selectivity of ion excretion).

The calculated values of the binding energy of nonapeptides with receptors in docking with their influence on reabsorption of osmotically free water in a rat bud in vivo were compared. Vasotocin and some its analogs were intramuscularly introduced to non-narcotized rat females of the Wistar line in doses from 0.1 pmol to 0.5 nmol/kg of body weight against the background of peroral water load (50 ml/kg of body weight). A significant correlation between the calculated interaction energy of peptides with V2-receptors and an increase of reabsorption of osmotically free water in the rat bud stimulated by injection of nonapeptides was found. The results evidence that alterations in rat bud in vivo caused by analogs of vasotocin and their interactions with V2-receptors can be accurately simulated.

The investigations of threshold frequency characteristics (TFC) of the visual analyzer and labor productivity were carried out during 105-d isolation of volunteers in an airtight module illuminated by LED lamps adjustable to personal psychophysiological needs. Software and calculation procedure were devised to assist the chromatic TFC-based determination of photometric parameters. Data of analysis of actual mood and vision contrast sensitivity when looking at a three-color image suggested that visual performance could be improved by achieving light color adequacy to TFC of individual vision. The results of experimental investigations showed once again efficiency of the proposed methods and their relevance to the objectives of the extended ground-based experiment simulating an exploration mission to Mars.

New analogs of some neurohypophyseal hormones (oxypressin, hydrin, glumitocin, vasotocin) have been synthesized. Experiments with injection of these peptides to rats showed that substitution of C-terminal glycinamide on beta-ethanolamine (glycinol) or ethylamine in 1-deamino-arginine vasotocin resulted in loss of natriuretic but not antidiuretic activity. Analogs of oxypressin and hydrin exhibited neither natriuretic activity nor ability to affect water reabsorption. Glumitocin analog induced renal sodium ion excretion and did not influence potassium ion excretion.

Injections of furosemide at a dose of 0.3 micromol per 100 g body weight or 1-deamino-arginine-vasotocin (1dAVT) at a dose of 0.05 nmol per 100 g body weight induced nearly equal increase in urinary sodium excretion: up to 406 +/- 20 and 405 +/- 23 micromol/2 h, respectively. Increase in urinary sodium excretion after injection of 1d-AVT was followed by enhancement of solute free water reabsorption from -0.51 +/- 0.05 to -2.75 +/- 0.11 ml/2 h (p0.05). On the contrary, furosemide injection induced a significant decrease in solute free water reabsorption to -0.19 +/- 0.06 ml/2 h (p0.05) and led to the appearance of solute free water in urine during peak of diuretic reaction. These data for the first time show that furosemide not only decreases sodium reabsorption, but also blocks some componentin molecular mechanism of vasopressin-dependent increase of the osmotic permeability of water.

Influence of enalaprilat, angiotensin converting enzyme inhibitor, on a functional proteinuria associated with increase in diuresis unduced by furosemide, 1-deamino-arginine vasotocin (1d-AVT) injection or water loading was investigated in experiments with Wistar rats. Intraperitoneal injection of 0.1 mg/100 g b.w. of enalaprilat resulted in reduction of glomerular filtration rate, solute-free water reabsorption and solutes excretion, particularly potassium excretion, after 1d-AVT administration and decrease in diuresis and solute-free water excretion after oral water loading. Enalaprilat injection did not influence on the level of proteinuria induced by the various types ofdiuresis and albuminuria during water diuresis and 1d-AVT-dependent saluresis. The data obtained have shown that decrease in angiotensin II production in the renal structures does not affect protein excretion rate during examined forms of proteinuria and suggest existence of a multicomponent system of the pressure stabilization in the glomerular apparatus.