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.

Mechanism of Natriuretic Effect of Oxytocin.

In rats, intramuscular injection of oxytocin (0.25 nmol/100 g body weight) increased sodium excretion from 19±5 to 120±11 µmol/min. A significant correlation (p<0.001) was revealed between renal excretion of oxytocin and sodium ions. Under the action of oxytocin, natriuresis was characterized by diminished reabsorption of fluid in the proximal tubule of the nephron attested by elevated lithium clearance rate and from stimulation of V1a receptors in the cells of thick ascending loop of Henle. Pmp-Tyr(Me)-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2, a V1a receptors antagonist, prevented the natriuretic effect of oxytocin.

[INFLUENCE OF OLEAMIDE OF WATER AND ION TRANSPORT IN THE OSMOREGULATORY ORGANS].

Application of oleamide (final concentration of 10 µM) at the skin basal surface of the frog, Rana temporaria L., augmented the short-circuit current (SCC) from 59.8 ± 2.5 to 78.2 ± 1.4 µA/cm2. Oleamide added to the serous membrane of the frog urinary bladder at a final dose of 1 µM induced more than 30-fold increase of osmotic permeability. The addition of arginine-vasotocin on the background of oleamide action further increased SCC across the isolated frog skin and osmotic permeability of the frog urinary bladder. Intraperitoneal injection of oleamide at a dose of 0.1 mM/100 g BW to water-loaded non-anesthetized Wistar rats decreased diuresis by 22%, enhanced solute-free water reabsorption and urinary sodium excretion by 31% and 55% respectively, but did not affect the renal potassium excretion. The results obtained provide evidence of similarity of oleamide and neurohypophyseal hormones effects on water and ion transport in epithelial cells of osmoregulatory organs in vertebrates.

[The effect of exenatide analogs on hydruretic function of rat kidney under water load].

Injection (0.05 nmol/100 g b.w.) of exenatide or its amino-acid-substituted synthetic analogs I (substitution at positions 14 and 39) and II (substitution at positions 14, 35, and 39) led to an increase in diuresis and excretion of sodium, magnesium and potassium, but only exenatide caused the excretion of solute free water. In experiments with 1% water load, only exenatide analog I stimulated the solute free water excretion. These features of exenatide and its analogs show the possibility of searching for substances with various power of action upon ion and water excretion by the kidney, which may have a clinical significance.

[Opposite actions of different doses of arginine-vasotocin and 1-deamino-arginine-vasotocin on sodium ion transport in skin of the frog Rana temporaria].

Active transport of sodium ions across the isolated abdominal skin of the frog Rana temporaria after application of arginine-vasotocin (AVT) and 1-deamino-arginine-vasotocin (1dAVT) was studied by measurement of the short-circuit current (SCC). The maximal increase in the SCC values (26 and 19 microA/cm2) was observed after addition of 10 nM AVT or 100 nM 1dAVT, respectively, to the frog skin basal surface. An increase of concentration of AVT to 100 nM and of IdAVT to 1 microM terminated the sodium transport in the frog skin. A preliminary addition of an antagonist of arginine-vasopressin V1a-receptors to the Ringer's solution at the frog skin basal surface led to a rise in the SCC values in response to administration of ineffective doses of AVT or 1dAVT. V2-receptor antagonists did not affect the frog skin reaction to administration of these doses of AVT or IdAVT.

[Selective effect of vasotocin analogues with amino acid substitutions in 4, 7, 8 positions on the water and cations excretion by the rat kidney].

Analogues ofarginine vasotocin with replacement of amino acids in 4, 7 and 8 positions of the hormone were synthesized. After water loading the injection of 1 x 10(-12) mol per 100 g BW 1-deamino-8-homoarginine vasotocin, 1-deamino-4-threonine-8-arginine vasotocin and 1-deamino-4-threonine-8-D-arginine vasotocin increased solute-free water reabsorption, but did not affect cations excretion (Na, K, Ca, Mg). Presence of glycine in 9th position and proline in 7th position ofa vasotocin molecule is essential for hormone interaction with a V2-receptor. In rats, injection of 5 x 10(-11) mol 1-deamino-8-homoarginine vasotocin or 1-deamino-4-threonine-8-arginine vasotocin dramatically increased urinary sodium and potassium excretion and enforced osmotically free water reabsorption but very little affected urinary magnesium and calcium excretion. The injection in the same dose of other synthesized vasotocin analogues did not affect the cations excretion. The issue of physiological mechanisms of kidney's selective response related to water, one- and bivalent cations excretion after injection of vasotocin analogues is discussed. Inhibition of cations transport is associated with activation of any V-receptor (but not V2-receptor). This effect takes place only in presence of L-arginine instead of D-arginine in the analogue.

[Comparative analysis of 1-desamino-arginine-vasotocin, 1-desamino-1-monocarba-arginine-vasotocin and desmopressin antidiuretic effect in rats].

This study was carried out to investigate the antidiuretic efficacy of 1-desamino-arginine-vasotocin (1-dAVT), 1-desamino-1-monocarba-arginine-vasotocin (1-dlmcAVT) in comparison with desmopressin in Wistar rats. Intramuscular injection of 0.0001 nmole/100 g body weight of desmopressin or synthesized analogues of arginine-vasotocin 5 % in the water loading resulted in significant reduction of urinary flow (p < 0.001) and later removed the diuresis maximum. The most expressed decrease of water excretion which was correlated with the diminished diuresis (r = -0.78,p < 0.001) was observed after injection of 0.0001 nmole/100 g body weight desmopressin. The equivalent increase of water reabsorbtion was induced by 0.00005 nmole/100 g body weight 1-dlmcAVT or desmopressin. The differences between excretion of osmotically active substances, sodium or potassium in the action of 1-dAVT, 1 -d-lmcAVT and desmopressin was not revealed.

[Role of prostaglandin E2 in regulation of urine excretion in saluresis, water and osmotic diuresis in rat]. / Issledovanie roli prostaglandina E2 v reguliatsii mocheobrazovaniia pri salureze, vodnom i osmoticheskom diurezakh u krys.

In the saluresis, water and osmotic diuresis were indicating an increase of prostaglandin E2 excretion and a correlation between this index and diuresis. Unselective blockade of cyclooxygenase by diclofenac-natrium leads to a decrease of diuresis in the observed types of urine-production in rats. Inhibition of inducible cyclooxygenase by celebrex didn't change the value of diuresis after water load or administration of osmotic agent, but decreased the diuretic effect of furosemide.

[Possible mechanisms of polyuria in progressive chronic renal failure]. / Vozmozhnye mekhanizmy poliurii pri progressiruiushchei khronicheskoi pochechnoi nedostatochnosti.

AIM: Elucidation of the role of saluresis and osmotic diuresis in renal function of patients with chronic renal failure. MATERIAL AND METHODS: The trial included 68 subjects, among them 25 patients with chronic renal failure (CRF) of the third and fourth degree aged 16 to 72 years. Enzyme immunoassay was used to measure osmolality, sodium, potassium, magnesium, calcium and creatinine concentrations in the serum and urine as well as urine prostaglandin E2. RESULTS: Renal function was studied in CRF patients with a 75-90% fall of glomerular filtration rate. Creatinine clearance was 19.9 +/- 0.96, it varied in different patients from 10.6 to 29.7 ml/min. It is shown that diuresis does not correlate with the total ion excretion (Na+ plus K+)(r = 0.946, p < 0.0001). A correlation was found between excretion of these ions and Mg2+ ions this indicating location of reabsorption reduction in the thick ascending limb of Henle loop. In CRF patients (Na+ plus K+) excretion correlated with PGE2 excretion (r = 0.65, p < 0.0001). CONCLUSION: It is suggested that at this stage of chronic renal failure the mechanism of a diuresis increase is not due to osmotic diuresis but rather to secretion of prostaglandin E2 which inhibits cation reabsorption and stimulates diuresis. Differences are considered between osmotic diuresis and different types of saluresis; their possible mechanisms are discussed.

Study of the role of prostaglandin E2 in urine flow regulation in chronic renal failure.

OBJECTIVE: This study was carried out to investigate the role of prostaglandin E2 in the regulation of urine flow and ion excretion in patients with chronic renal failure. MATERIAL AND METHODS: Twenty patients with chronic renal failure (CRF) and 13 healthy people were studied. CRF develops as a terminal stage of glomerulonephritis, pyelonephritis or polycystic renal disease. Osmolality and sodium, potassium, magnesium, calcium and creatinine concentrations were measured in urine and blood serum. Urine prostaglandin E2 was determined using kits for imminoenzyme analysis. RESULTS: The average creatinine clearance was 19.9 +/- 6.3 ml/min, but it varied from 30 to 10 ml/min in different patients. In patients with CRF a correlation was revealed between diuresis and Na excretion (r = 0.78, p < 0.001) and between Na excretion and PGE2 excretion (r = 0.65, p < 0.001), a correlation that lacking in the healthy subject. A correlation was also found between diuresis and Mg excretion (r = 0.68, p < 0.001) and between Mg excretion and Na excretion (r = 0.83, p < 0.001) in patients with CRF but not in healthy subject. CONCLUSION: It is suggested that in patients with CRF who experience a decrease in the glomerular filtration rate (to 75-90% of the normal value) the increase in urine flow is due to prostaglandin-dependent inhibition of ion reabsorption in the thick ascending limb of the loop of Henle.

[Mechanism f kidney participation in maintaining osmotic and ion homeostasis in chronic renal failure]. / Mekhanizm uchastiia pochki v obespechenii osmoticheskogo i ionnogo gomeostaza pri khronicheskoi pochechnoi nedostatochnosti.

In examination of patients with chronic renal failure (CRF) at glomerular filtration rate below 30 ml/min and blood serum ion concentration within limits of normal values hyperosmia has been found. Under the natural regimen essential differences have been revealed neither in variation limits of renal excretion of ions nor osmotically active substances in CRF patients as compared with healthy controls. Diuresis correlated with renal excretion of osmotically active substances. It is shown that a decrease in reabsorption of osmotically active substances depends on secretion and excretion of prostaglandin E2. A suggestion is made about the role of prostaglandins in regulation of renal tubular function at terminal CRF stages.

[The effect of cyclooxygenase inhibitors on ion and water transport in the human kidney and frog skin and bladder]. / Vliianie ingibitorov tsiklooksigenazy na transport ionov i vody v pochve cheloveka, kozhe i mochevom puzyre liagushki.

In the frog urinary bladder and skin, block of cyclooxygenase with diclofenac (voltaren) resulted in an increase in the water permeability and a decrease in the potential difference and short-circuit current. Addition of 0.01 mumole of prostaglandine E2 decreased the osmotic water permeability to initial values and increased the transepithelial ion transport in the frog skin. In the kidney of children with nocturnal enuresis there was an increase in the night diuresis and in excretion of osmotically active substances. Voltaren by reducing the endogenous autacoid production, restored the kidney function and symptoms of enuresis disappeared. The results obtained indicate an important role of the rate of the endogenous autacoid production in regulation of the water and ion transport in the osmoregulating organs studied.