Regulation Of Water Excretion Research Articles

Clinical and pathophysiological aspects of impaired water and sodium metabolism in newborns and neurological complication

This literature review covers the pathophysiological features of water and sodium exchange in newborns. The main mechanisms regulating fluid and electrolyte balance in newborns are poorly studied. The volume and composition of the extracellular fluid are provided by the functional activity of the kidneys under the control of the neuroendocrine system. The antidiuretic hormone plays the main role in the regulation of water excretion by the kidneys. The volume of intracellular fluid depends on the passive water transport with the participation of aquaporins. Lability of water and electrolyte metabolism in newborns may be accompanied by hyponatremia. For various pathological conditions in the neonatal period, certain types of hyponatremias are characteristic. Correction of hyponatremia should be carried out taking into account its pathophysiological type. Hyponatremia is a common complication associated with severe neonatal brain damage. Hyponatremia contributes to brain damage as an independent factor. The study of indicators of water and electrolyte balance in the neonatal period has an important prognostic value for early detection of damage to the central nervous system.

Differential circadian pattern of water and Na excretion rates in the metabolic syndrome

This study comparatively investigated the chronobiology of water and Na excretion rates (W-ExcR and Na-ExcR) in 46 non-diabetic metabolic syndrome (MS) patients. The circadian pattern of W-ExcR was independently associated with the nocturnal dipping of systolic blood pressure (β = −3.1). During oral glucose tolerance test, the rise in plasma insulin (β = 34.0) and the insulinogenic index (β = 4.1) were independently associated with the day/night ratio of W-ExcR. The circadian pattern of Na-ExcR was not significantly associated with the latter variables. This study strongly suggests that the chronobiology of mechanisms involved in the regulation of water excretion may be more specifically altered in the MS.

Body sodium and volume homeostasis.

maintenance of a “milieu interieur,” which allows our cells to function away from the ancient sea, is one of the most important functions of the body. Maintenance of constant extracellular osmolarity and sodium concentration depends on a precise balance between intake and excretion of sodium and

Impact of the endothelin system on water and sodium excretion in patients with liver cirrhosis

Impaired renal function in patients with liver cirrhosis is a serious complication and is characterized by sodium and water retention in the absence of identifiable specific causes of renal dysfunction. The endothelin system has been shown to be activated in liver cirrhosis and might contribute to impaired renal function. However, the mechanisms leading to an activation of the endothelin system in these patients and the effects of an activated endothelin system on renal function in these patients are as yet unknown. To determine the correlation between the activity of the endothelin system and the ability to excrete water and sodium in patients with liver cirrhosis, we measured plasma endothelin-1 concentrations by reversed phase-HPLC followed by an endothelin RIA and performed an oral water load tests in 10 healthy control subjects and 43 patients with liver cirrhosis. In addition, we analysed possible mechanisms/factors like plasma endotoxin that might contribute to the activation of the endothelin system in liver cirrhosis. This study showed that the endothelin system is activated in patients with liver cirrhosis in a disease-stage-dependent manner. Patients with Child C liver cirrhosis have a 5.45-fold increased plasma ET-1 concentration compared to healthy controls, whereas plasma ET-1 is only increased 2.74-fold in Child A patients. An oral water load test revealed a highly significant (P < 0.0001) inverse correlation between the plasma endothelin-1 concentrations and the ability to excrete a given water load. Plasma endotoxin, a well-known stimulus of ET-1, is significantly (P < 0.03) correlated with plasma ET-1 in cirrhotic patients. The ET-1 concentrations in the ascites of patients with liver cirrhosis were lower and not related to plasma ET-1. The activity of the endothelin system in patients with liver cirrhosis depends on the severity of liver impairment. Plasma endotoxin might be an important stimulus of the endothelin system in liver cirrhosis. We observed a highly significant inverse correlation between the plasma endothelin-1 concentrations and the ability to excrete a given water and sodium load, suggesting that the endothelin system plays a role in the regulation of water excretion in patients with liver cirrhosis.

Vasopressin type-2 receptor and aquaporin-2 water channel mutants in nephrogenic diabetes insipidus.

The regulation of water excretion by the kidney is one of the few physiologic processes that are prominent in everyday life. This process predominantly occurs in renal collecting duct cells, where transcellular water reabsorption is induced after binding of the pituitary hormone arginine-vasopressin to its vasopressin type-2 receptor and the subsequent insertion of aquaporin-2 (AQP2) water channels in the apical membrane of these cells. Removal of the hormone triggers endocytosis of AQP2 and restores the water-impermeable state of the collecting duct cells. Nephrogenic diabetes insipidus is characterized by the inability of the kidney to concentrate urine in response to vasopressin; the vasopressin type-2 receptor and the AQP2 water channel have both been shown to be involved in this disease. This article focuses on mutations in the vasopressin V2 receptor and aquaporin-2 water channel identified in nephrogenic diabetes insipidus patients, and on the effects of these mutations on the transport and function of these proteins upon expression in cell systems.

Vasopressin Type-2 Receptor and Aquaporin-2 Water Channel Mutants in Nephrogenic Diabetes Insipidus

The regulation of water excretion by the kidney is one of the few physiologic processes that are prominent in everyday life. This process predominantly occurs in renal collecting duct cells, where transcellular water reabsorption is induced after binding of the pituitary hormone arginine-vasopressin to its vasopressin type-2 receptor and the subsequent insertion of aquaporin-2 (AQP2) water channels in the apical membrane of these cells. Removal of the hormone triggers endocytosis of AQP2 and restores the water-impermeable state of the collecting duct cells. Nephrogenic diabetes insipidus is characterized by the inability of the kidney to concentrate urine in response to vasopressin; the vasopressin type2 receptor and the AQP2 water channel have both been shown to be involved in this disease. This article focuses on mutations in the vasopressin V2 receptor and aquaporin-2 water channel identified in nephrogenic diabetes insipidus patients, and on the effects of these mutations on the transport and function of these proteins upon expression in cell systems.

Localization and regulation of the rat renal Na(+)-K(+)-2Cl- cotransporter, BSC-1

To investigate the role of the thick ascending limb (TAL) Na(+)-K(+)-2Cl- cotransporter in regulation of water excretion, we have prepared a peptide-derived polyclonal antibody based on the cloned cDNA sequence of the rat type 1 bumetanide-sensitive cotransporter, BSC-1 (also termed "NKCC-2"). Immunoblots revealed a single broad 161-kDa band in membrane fractions of rat renal outer medulla and cortex but not from rat colon or parotid gland. A similar protein was labeled in mouse kidney. Immunoperoxidase immunohistochemistry in rat kidney revealed labeling restricted to the medullary and cortical TAL segments. Because long-term regulation of urinary concentrating ability may depend on regulation of Na(+)-K(+)-2Cl- cotransporter abundance, we used immunoblotting to evaluate the effects of several in vivo factors on expression levels of BSC-1 protein in rat kidney outer medulla. Chronic oral saline loading with 0.16 M NaCl markedly increased BSC-1 abundance. However, long-term vasopressin infusion or thirsting of rats did not affect BSC-1 abundance. Chronic furosemide infusion caused a 9-kDa upward shift in apparent molecular mass and an apparent increase in expression level. These results support the previous identification of BSC-1 as the TAL Na(+)-K(+)-2Cl- transporter and demonstrate that the expression of this transporter is regulated.

Paracrine renal endothelin system in rats with liver cirrhosis.

1. Liver cirrhosis was induced in rats by CCl4 administration. We analysed the expression of endothelin receptor subtypes in the renal cortex and medulla using Scatchard analysis and receptor autoradiography, and measured plasma as well as renal-tissue endothelin-1 concentrations using a specific radioimmunoassay. Furthermore, we analysed the effects of the non-selective (A/B) endothelin receptor antagonist, bosentan (6 and 100 mg kg-1 day-1) on mean arterial blood pressure, water and sodium excretion and glomerular filtration rate. 2. Our study revealed an overexpression of the endothelin B receptor (ETB) in the renal medulla of rats with liver cirrhosis (Cir: 2775 +/- 299 fmol mg-1; Con: 1695 +/- 255 fmol mg-1; n = 8; means +/- s.d., P < 0.01), whereas the density of ETB in the cortex and the endothelin A receptor (ETA) in the cortex and medulla were similar in both cirrhotic and control rats. Receptor autoradiography showed that the upregulation of medullary ETB in cirrhotic rats was due to an upregulation of ETB in the inner medullary collecting duct cells. 3. The tissue endothelin-1 concentrations were increased in the renal medulla of cirrhotic rats (Cir: 271 +/- 68 pg g-1wet wt.; Con: 153 +/- 36 pg g-1 wet wt., n = 8; means +/- s.d., P < 0.01). 4. The glomerular filtration rate was slightly decreased in cirrhotic rats but not altered after bosentan treatment in either cirrhotic or control rats. Bosentan decreased sodium excretion to a similar extent in both cirrhotic and control rats, whereas water excretion was significantly reduced by both dosages of bosentan in cirrhotic rats only (Cir + vehicle: 12.5 +/- 0.62 m day-1, Cir + 6 mg kg-1 day-1 bosentan: 8.6 +/- 1.0 ml day-1; Cir + 100 mg kg-1 day-1 bosentan: 7.4 +/- 0.6 ml day-1; n = 10; means +/- s.e.mean). 5. We therefore suggest that the upregulation of the medullary ETB in cirrhotic rats is involved in the regulation of water excretion in rats with CCl4-induced liver cirrhosis.

Renal Endothelin System in Rats with Liver Cirrhosis

Rats with experimental liver cirrhosis have increased endothelin-1 (ET-1) plasma concentrations and show a tendency toward sodium and water retention. We therefore analyzed the renal ET system in cirrhotic rats and control rats, as the renal ET system is involved in the regulation of water and sodium excretion. Cirrhosis was induced by carbon tetrachloride (CCl4) administration. We analyzed the expression of ET receptor subtypes in the renal cortex and medulla using Scatchard analysis and receptor autoradiography, and measured plasma and renal tissue ET-1 concentrations using a specific radioimmunoassay. Furthermore, we analyzed the effects of the nonselective (A/B) ET receptor antagonist bosentan on water and sodium excretion and glomerular filtration rate. Our study revealed an overexpression of the ETB receptor in the renal medulla of rats with liver cirrhosis, whereas the density of ETB receptor in the cortex and the ETA receptor in the cortex and medulla were similar in both cirrhotic and control rats. Receptor autoradiography showed that the upregulation of medullary ETB in cirrhotic rats was due to an upregulation of ETB in the inner medullary collecting duct cells. The highest ET-1 concentrations were observed in the renal medulla of cirrhotic rats. Glomerular filtration rate decreased in cirrhotic rats but was not altered after bosentan treatment in cirrhotic and control rats. Bosentan decreased sodium excretion in both cirrhotic and control rats to a similar extent, whereas water excretion was reduced by bosentan only in cirrhotic rats. We therefore suggest that the upregulation of medullary ETB in cirrhotic rats is involved int he regulation of water excretion in rats with CCl4-induced cirrhosis.

Effect of dopamine antagonists on the urine flow of rats infused with hypotonic saline.

1. The probable involvement of dopamine in the regulation of water excretion was investigated by administering dopamine antagonists intravenously to barbiturate--anaesthetized rats undergoing a water diuresis induced by the infusion of 0.83% glucose with 0.3% NaCl at the rate of 9 ml h-1. 2. Administration of 100 micrograms of the D1-/D2-dopamine antagonist, haloperidol, reduced the enhanced urine flow of rats infused with the hypotonic solution by 69% (from 75.4 +/- 13.0 to 23.6 +/- 6.0 microliter min-1, P less than 0.01). Similarly, the D1-receptor antagonist, SCH 23390, reduced urine flow by 58% (from 77.5 +/- 9.2 to 32.7 +/- 7.2 microliters min-1, P less than 0.01) and the D2-receptor antagonist, sulpiride, by 47% (from 66.2 +/- 8.6 to 35.1 +/- 6.8 microliter min-1, P less than 0.05). 3. The injection of SCH 23390 increased the urine osmolality from 189.6 +/- 27.5 to 479.8 +/- 45.8 mosm kg-1 (P less than 0.05). There was no significant change in sodium and potassium excretion in any of the experiments. Blood pressure (BP) decreased after haloperidol and SCH 23390 injection from control values of 121.7 +/- 1.7 and 116.5 +/- 7.4 to 113.3 +/- 3.3 and 106.0 +/- 8.8 mmHg respectively (P less than 0.05). 4. To study whether the influence of dopamine antagonists on urine flow during water diuresis depends on antidiuretic hormone (ADH), we administered 0.6 micrograms d(CH2)5-D-Phe-Ile-AVP (an ADH antagonist) shortly after the injection of 100 micrograms SCH 23390. The preferential V2 ADH-antagonist abolished the antidiuretic effect of SCH 23390 but did not affect its blood pressure reducing effect (from 118.6 +/- 5.6 to 103.2 +/- 4.6 mmHg, P <0.01). 5. These results suggest that dopamine antagonists blunted the hypotonic saline-induced diuresis by favouring ADH release through an interference with an inhibitory dopaminergic pathway.

Excretion of 6-keto-PGF 1α and PGE 2 in rats with hereditary hypothalamic diabetes insipidus

We measured the urinary excretion of a stable metabolite of prostacyclin, 6-keto-PGF 1α, and of PGE 2 in homozygous Brattleboro rats, a strain with hereditary hypothalamic diabetes insipidus. Excretion of both prostaglandins was largely increased compared to both heterozygous Brattleboro rats and Long-Evans rats. These results are in contrast to previously published observations demonstrating a subnormal excretion of PGE 2 in Brattleboro rats. It is suggested that prostaglandin synthesis may be under tonic inhibitory control by vasopressin both in the kidney and in the endothelial cells of blood vessels. The findings further support the view that prostaglandins play an important role in the regulation of water excretion and in the pathogenesis of polyuric conditions.

Urinary kallikrein and changes in endogenous aldosterone in the rat

Abstract. Urinary kallikrein excretion was studied during changes in sodium intake. The effect of short‐term (5 days) and long‐term (4 weeks) sodium restriction was also investigated. In order to provide additional evidence for a primary role of endogenous aldosterone on the renal kallikrein system, the effect of dietary potassium restriction was studied in chronically sodium depleted rats. Chronic (4 weeks) sodium restriction was associated with high urinary kallikrein excretion (6.21 ± 0.31 i.u./24 h/100 g body weight). Urinary kallikrein was lower in high salt and normal salt rats (2.38 ± 0.18 and 2.71 ± 0.18 i.u./24 h/100 g bw). A negative correlation (r= ‐0.88, P&lt;0.001) between urinary kallikrein and the logarithm of natriuresis was obtained. Positive correlations between urinary kallikrein and diuresis were obtained within each group of rats equilibrated with different sodium intakes. When chronically sodium loaded rats were given a low sodium diet for a 5‐day period, urinary kallikrein increased from 1.99 ± 0.17 to 3.64 ± 0.3 i.u./24 h/100 g bw (P&lt;0.001). The mean value achieved after 5 days of sodium restriction was significantly lower (P&lt;0.001) than the value obtained in long‐term (4 weeks) sodium depleted rats. When low sodium rats were fed a low sodium‐low potassium diet for 7 days, urinary kallikrein decreased by 34 ± 8% (P&lt;0.005) and urinary aldosterone fell from 112 ± 27 to 43 ± 11 ng/24 h (P&lt;0.01). Natriuresis remained constant throughout the study. These results suggest that endogenous aldosterone is one of the main determinant of renal kallikrein activity. Kallikrein may participate in the regulation of water excretion. In addition, the kallikrein‐kinin system may be involved in the renal adaptation to long‐term sodium restriction in the rat.

Hormonal control of renal water excretion

Antidiuretic hormone (ADH) is clearly the hormone of paramount importance in the regulation of water excretion by the mammalian kidney. However, other hormones also influence renal water excretion and this portion of the symposium will examine how some of these hormones exert their effects. Because of the interrelationships of endocrine systems in homeostasis, almost any known hormone might be construed as having some effect; however, we shall consider here only those hormones which are thought to have major effects on renal handling of water. In theory, these effects might be mediated directly by hormonal alteration of renal tubular permeability to water, renal hemodynamics, tubular fluid and plasma electrolyte concentrations, collecting duct sensitivity to ADH or tubular fluid delivery to concentrating and diluting segments of the nephron. As will be apparent from this review, some hormones are known to combine several of these actions while the actions of others remain uncertain.