Hydruric response in Wistar and vasopressin-deficient Brattleboro rats to water load under conditions of increased brain serotonin level.

The hydruric response to water load in Wistar rats and homozygous Brattleboro rats with a hereditary defect in the synthesis of vasopressin was studied under conditions of increased brain serotonin level. Serotonin prevented the reduction in reabsorption of osmotically free water in normal rats, but had no effect in vasopressin-deficient Brattleboro rats. Our results suggest that serotonin stimulates vasopressin secretion and interacts with the vasopressinergic system during the realization of osmotic regulation.

[Osmoregulating reactions following serotonin metabolism inhibition or activation]. / Realizatsiia osmoreguliruiushchikh reaktsii v usloviiakh podavleniia i aktivatsii metabolizma serotonina.

Effect of p-chlorphenilalanine and 5-hydroxytriptophan on the urine flow (V), glomerular filtration rate (GFR), free water reabsorption (TCH2O), and sodium fraction excretion (ENa.F%) in Wistar rats loaded with water or 2% sodium chloride solution, was studied. It was found that treatment of rats with inhibitor of serotonin biosynthesis, p-chlorphenilalanine (300 mg/kg, 48 hrs before the experiment) had no effect on the kidney response to the water loading in the experimental rats as compared to the control ones: changes in V, GFR, TCH2O and ENa.F% were the same. Treatment of rats with precursor of serotonin, 5-hydroxytriptophan which is known to increase the serotonin level in the brain (50 mg/kg) simultaneously with the water loading prevented the development of the diuretic reaction because of the high level of TCH2O reflected in the blood vasopressin concentration. Injection of 5-hydroxytriptophan at the maximum level of water diuresis resulted in the sharp increase in TCH2O and drop of the V. 5-hydroxytriptophan had no significant effect on the kidney response to the loading with the 2% sodium chloride solution. Under these conditions, increase in V was produced by suppression of the distal tubular sodium reabsorption, the TCH2O remaining at the high level. It is suggested that the brain serotonin manifested a significant stimulating effect on the vasopressin release from the neurohypophysis, but it is not involved in the mechanisms of suppression of its release into the blood. Serotonin seems not to interact with brain mechanisms regulating natriuretic function of the kidney.

Hypothalamic tryptophan hydroxylase and the hypothalamic-pituitary-adrenocortical response to water deprivation and hydration in vasopressin-deficient and normal rats.

The effects of water deprivation and hydration on plasma corticosterone concentration and the activity of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin (5-HT) biosynthesis, in the hypothalamus of vasopressin- (AVP-) deficient homozygous Brattleboro and normal Wistar rats were studied. In the Wistar rats, water deprivation caused an increase in the TPH activity in the anterior and middle (infundibular) parts of the hypothalamus, while hydration did not affect the activity of the enzyme in the anterior hypothalamus but produced an increase in its middle part. In contrast, in the Brattleboro rats, water deprivation had no effect on TPH activity in the anterior and middle parts of the hypothalamus but hydration produced a decrease in TPH activity in the anterior hypothalamus. After 48 h of water deprivation, the plasma corticosterone concentration significantly increased in water-deprived and decreased in hydrated Wistar rats. Under water deprivation, the rise in corticosterone concentration in the homozygous Brattleboro rats was significantly greater than that in the Wistar rats. The data provide evidence that the CRH-like activity of AVP is not necessary for activation of the hypothalamic-pituitary-adrenal system induced by water deprivation. The observations show that AVP is involved in the activation of TPH induced by water deprivation. This suggests that AVP modulates the metabolism of 5-HT and the response of the 5-HT-ergic system to water deprivation.

Effects of vasopressin on hyaluronate hydrolase activities and water permeability in the frog urinary bladder.

The involvement of enzymes catabolizing hyaluronic acid (hyaluronidase, beta-glucuronidase, N-acetyl-beta-D-hexosaminidase) in the hydroosmotic effect of vasopressin in the frog (Rana ridibunda) urinary bladder was studied. It was observed that vasopressin (50 nM), an agonist of V2 receptors, L-desamino-8-D-arginine-vasopressin (dDAVP, 1.5 microM) and forskolin (30 microM) activated the enzymes and caused their release into Ringer solution at the mucosal side, together with an increase in osmotic water flow. The effect of AVP on enzyme activity developed 10 min after the hydroosmotic response. Cytochalasin B (a specific inhibitor of actin filament elongation, 50 nM) blocked the hydroosmotic response to AVP; hyaluronate hydrolase activity increased in the bladder tissue but not in Ringer solution. It is suggested that the involvement of hyaluronate hydrolases in AVP's effect is mediated by a cAMP-dependent mechanism and provides favorable conditions for an increase in the permeability of glycosaminoglycan structures adjacent to the apical cell surface.

Brain serotonin metabolism during water deprivation and hydration in rats.

The effects of two-day water deprivation and hyperhydration (provision of 4% sucrose solution for 48 h) on levels of serotonin and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the midbrain and hypothalamus were studied in Wistar rats. The rates of diuresis (0.05 +/- 0.01 and 0.84 +/- 0.12 ml/h/100 g in water deprivation and hyperhydration respectively) and urine osmolality (1896 +/- 182 and 50 +/- 13 mOsm/kg) reflected increases and decreases in blood vasopressin levels. Water deprivation was associated with a significant increase in 5-HIAA levels in the midbrain and hypothalamus, along with a decrease in serotonin levels and a three-fold increase in serotonin catabolism (the 5-HIAA:serotonin concentration ratio). Hyperhydration induced moderate increases in serotonin and 5-HIAA levels in the hypothalamus with no changes in the midbrain. The blood corticosterone level doubled in water deprivation and decreased in hyperhydration. It is suggested that activation of the serotoninergic system induces a complex adaptive reaction in water deprivation. including mechanisms specific for the regulation of water-electrolyte homeostasis and non-specific stress mechanisms (vasopressin and corticoliberin secretion).

[Serotonin metabolism in the rat brain during water deprivation and hydration]. / Metabolizm serotonina v mozgu pri vodnoi deprivatsii i gidratatsii krys.

Water deprivation (WD) decreased the serotonin (5-HT) level and significantly increased the 5-hydroxyindoleacetic acid (5-HIAA) in the rat midbrain and hypothalamus, the catabolic 5-HIAA/5-HT ratio increasing three-fold. Hydration (H) produced a moderate increase in the 5-HT and 5-HIAA levels in the hypothalamus with no changes in the 5-HIAA/5-HT ratio. Hydration exerted no significant effect upon the 5-HT level and metabolism in the midbrain. A two-fold increase of corticosterone concentration in water deprivation and its decrease in hydration were shown to occur in peripheral blood plasma.

[Hyaluronate-hydrolases system and hydroosmotic effect of vasopressin]. / Sistema gialuronat-gidrolaz v gidroosmoticheskom éffekte vazopressina.

Involvement of enzymes catabolizing hyaluronic acid (hyaluronidase, beta-glucuronidase, N-acetyl-beta-D-hexosaminidase) in the hydroosmotic action of vasopressin on the amphibian urinary bladder Rana Ridibunda was studied. It was found that vasopressin (50 nM), agonist of V2 receptors dDAVP (1.5 mcM) and forscolin (30 mcM) induce an activation of enzymes and its release into the Ringer solution at the mucosal surface simultaneously with the increase in the osmotic water flow. Maximal effect was observed 10 min later than hydroosmotic response. Release of enzymes under vasopressin effect was found in the absence of osmotic gradient and water flow through the epithelium. The repeated substitution of the outer Ringer solution for the fresh one resulted in the increase in the both the water permeability and the release of enzymes through the mucosal surface. We suggested that involvement of hyaluronate-hydrolases in the vasopressin effect is mediated by the cAMP-dependent mechanism. It is supposed that this effect creates conditions for the increase in the permeability of glycosaminoglycan structures covering adjacent to the apical cell surface.

[Hormonal regulation of sodium excretion by the kidneys during hunger therapy of obese patients]. / Gormonal'naia reguliatsiia ékskretsii natriia pochkami pri lechenii golodaniem bol'nykh ozhireniem.

Sodium excretion and the blood levels of aldosterone, renin, atrial natriuretic peptide (ANP), and insulin were investigated in 9 women with obesity of alimentary-constitutional type during hunger therapy and resumed nutrition. It has been assumed that restricted sodium excretion with the kidneys during fasting is mainly caused by activation of the renin-angiotensin-aldosterone system, with ANP contributing to it, insulin not playing the major role in this process.

[The effect of early postnatal sympathectomy on kidney concentrating function in rats]. / Vliianie rannei postnatal'noi desimpatizatsii na kontsentriruiushchuiu funktsiiu pochki krysy.

Renal concentrating function has been studied in adult Wistar rats after injections of guanethidine (25 mg/kg) or physiological saline (control) to 1-30 days old rat puppies. Urine osmolality in 30- and 60-day guanethidine-treated rats after test injections of ADH (pituitrin, 5 microU/g) or after water deprivation for 24 h was higher than in control animals. Concentrations of potassium, sodium, and urea were practically equal in all the zones of renal tissue from both groups of rats. The data obtained indicate that renal efferent nerves do not affect significantly the formation of renal concentrating function. It is suggested that elimination of influences of alpha 2-adrenoreceptors, which are antagonistic to the effect of ADH, accounts for the observed increase in antidiuretic effect.

[Vasopressin: the ontogeny of antidiuretic action at the cellular level]. / Vazopressin: ontogenez antidiureticheskogo deistviia na kletochnom urovne.

The data on the development of molecular mechanism of the antidiuretic effect of vasopressin and the molecular structure of the AVP receptor, cytosolic cAMP-dependent protein-kinases and renal response to AVP, are discussed. The experiments were performed in normal rats and mice, nephrogenic diabetes insipidus mutants and rats treated with cortisol in early postnatal period. The development of the kidney sensitivity to AVP seems to be closely connected with the development of the molecular structure of the AVP receptor, age-related increase of the AVP-activated adenylate cyclase, and the maturation of cAMP-dependent protein kinases.

Changes in kidney response to ADH under hypogravity: rat models and possible mechanisms.

Brattleboro homo- (DI) and heterozygous (HZ) rats with total or partial deficiency of the antidiuretic hormone (ADH) and also 10-14-day old Wistar rats irresponsive to ADH were used to examine the possible causes of inadequate responses to ADH in cosmonauts after space flights and in humans after prolonged bedrest in antiorthostasis (-60). The experimental results suggested that changes in the intrarenal osmotic gradients, as well as in the aggregate state of the ADH receptors as a result of the decreased ADH blood level under hypogravitation, might be a cause of the inadequate response to ADH in cosmonauts during readaptation to the Earth's gravity.

The response to water-salt loading: sodium metabolism in spontaneously hypertensive rats.

The natriuretic response to loading with Ringer solution or 2% NaCl solution (5% of b.w.) was exaggerated in conscious rats with spontaneous hypertension (SHR) as compared to normotensive Wistar Kyoto rats (WKR). The content of bound sodium in the extracellular fraction was found to be increased in SHR as compared to WKR. The changes in the kinetics of sodium exchange were similar to those observed in Wistar rats maintained on a high sodium diet. The accumulation of sodium in the extracellular bound fraction and its saturation of the tissue pools may be involved in the development of the exaggerated natriuretic response to acute sodium loading produced in SHR.

Volume and ion regulating renal functions in the big gerbil (Rhombomys opimus L.) and the water vole (Arvicola terrestris L.).

1. After iso-osmotic salt loading (1% NaCl, 1.25% KCl, 0.75% MgCl2 solutions, each load making up 5% body weight) the water voles excreted 66.2% sodium, 84.4% potassium, 18.8% magnesium over a 4 hr period. The big gerbil excreted 20%, 58.9% and 7.1% respectively over the same period. The volume of the water excreted was greater in the case of the water vole. 2. There were no considerable changes in plasma ion concentration in rodents of the species studied after salt loading. 3. The gerbils and water voles had no significant changes in the renal cortex electrolyte concentrations as a result of isotonic salt loads. The highest sodium cortico-papillar gradient was found in the gerbils when experimenting with the isotonic NaCl loading. It was somewhat lower with the KCl load, and significantly lower with water and MgCl2 loads. 4. Under the same experimental conditions, no major changes in the papilla sodium concentration were found in the water voles. 5. The concentrations of potassium, calcium and magnesium were practically alike in all zones of the renal tissue of both rodent species, ion loads producing no effect. 6. The comparison of the renal volume and ion regulating function in rodents with different urine osmotic concentration systems proves the independent existence of renal functions. The greater rate of renal fluid and ion excretion in the water voles is coupled with less specific ion regulation.

[Adaptive evolution of osmoregulation in rodents with different ecologies]. / O adaptivnoi évoliutsii osmoreguliatsii u gryzunov s razlichnoi ékologiei

Studies have been made on osmoregulation in aquatic rats (Arvicola terristris), cotton rats (Sigmodou hispidus) and Wistar albino rats under the conditions of usual salt-water regimen and 3-day water deficiency. In water-loving rodents, water deficiency results in significant changes in blood constants which charasterize osmotic homeostasis (sodium and urea concentration, the osmolarity). In albino rats, the state of dehydration is accompanied by a significant increase in antidiuretic activity of the blood serum and by an increase in osmotic concentrating index up to 7.4 +/- 0.2. In A. terestris and S. hispidus, despite of the increase in antidiuretic activity of the blood serum, no significant increase in U/Posm was found (2.7 +/- 0.2 and 4.8 +/-0.3 respectively). Low effectiveness of osmotic concentration in water-loving rodents is due to structural and functional rearrangement of the concentrating mechanism of the kidney, and, as a result, to the decrease in intrarenal gradients of sodium and urea. These peculiarities determine ecological specialization of osmoregulatory system.

[The role of renal acid mucopolysaccharides in the mechanism of reabsorption of osmotically free water]. / O roli kislykh mukopolisakharidov pochki v mekhanizme reabsorbtsii osmoticheski svobodnoî vody

The authors compared the histochemical characteristics of acid mucopolysaccharides (MPS) of the medulla of the kidney with functional indices of the latter in dogs under conditions of water, osmotic diuresis and in polyuria caused by the administration of heparin. There was seen a correlation between the changes in the MPS staining and the intensity of reabsorption of osmotically free water. On the basis of the results obtained a supposition was put forward that the change in the physico-chemical properties of the MPS served as one of the most significant factors determining the permeability of the medulla structures for the passage of water from the tubular lumina into the interstitium.