Aldosterone increases urine production and decreases apical AQP2 expression in rats with diabetes insipidus

2006 ◽  
Vol 290 (2) ◽  
pp. F438-F449 ◽  
Author(s):  
Jakob Nielsen ◽  
Tae-Hwan Kwon ◽  
Jeppe Praetorius ◽  
Jørgen Frøkiær ◽  
Mark A. Knepper ◽  
...  
Keyword(s):  
Creatinine Clearance ◽  
Diabetes Insipidus ◽  
Free Water ◽  
Sodium Balance ◽  
Apical Plasma Membrane ◽  
Sodium Reabsorption ◽  
Outer Medulla ◽  
Free Water Clearance ◽  
Urine Production ◽  
Water Clearance

Vasopressin and aldosterone are essential hormones in the regulation of water and sodium balance. Aldosterone regulates sodium reabsorption, although synergistic effects on collecting duct water permeability have been shown. We investigated the effects of 7-day aldosterone infusion or oral spironolactone treatment on water balance and aquaporin (AQP) 2 expression in rats with 21 days of lithium-induced nephrogenic diabetes insipidus (Li-NDI). In rats with Li-NDI, aldosterone markedly increased (271 ± 14 ml/24 h), whereas spironolactone decreased (74 ± 11 ml/24 h) urine production compared with rats treated with lithium only (120 ± 11 ml/24 h). Aldosterone increased free-water clearance and creatinine clearance, whereas spironolactone caused a decreased creatinine clearance but unchanged free-water clearance. Immunoblotting showed unchanged AQP2 expression in cortex/outer stripe of the outer medulla and inner medulla. In the inner stripe of the outer medulla aldosterone caused a decreased AQP2 expression, whereas spironolactone caused an increase compared with rats treated with lithium only. Semiquantitative confocal immunofluorescence microscopy of AQP2 immunolabeling showed reduced AQP2 expression in the apical plasma membrane domain in connecting tubule (CNT) and initial cortical collecting ducts (iCCD) in response to aldosterone-treated rats compared with rats treated with lithium only. Spironolactone significantly increased apical AQP2 expression in the iCCD compared with rats treated with lithium only. We also tested whether similar changes could be observed in vasopressin-deficient BB rats and found similar changes in urine production and subcellular AQP2 expression in the CNT and iCCD in response to aldosterone and spironolactone. This study shows that aldosterone treatment perturbs diabetes insipidus and is associated with AQP2 redistribution in CNT and iCCD likely mediated by the spironolactone-sensitive mineralocorticoid receptor.

RENAL DIURESIS AFTER INJECTIONS OF THE FRESHWATER EEL AND ANTIDIURESIS ARGININE VASOTOCIN IN (ANGUILLA ANGUILLA L.)

1974 ◽  
Vol 61 (3) ◽  
pp. 487-500 ◽  
Author(s):  
I. W. HENDERSON ◽  
N. A. M. WALES
Keyword(s):  
Body Weight ◽  
Glomerular Filtration ◽  
Free Water ◽  
Anguilla Anguilla ◽  
Arginine Vasotocin ◽  
Free Water Clearance ◽  
Response Characteristics ◽  
Arterial Blood ◽  
Urine Production ◽  
Water Clearance

SUMMARY The renal responses of the freshwater-adapted eel, Anguilla anguilla L. to arginine vasotocin ([8-arginine]-oxytocin) have been examined. The quality of the responses to the intravenously administered peptide was found to vary with the dose. Less than 0·1 ng/kg body weight reduced glomerular filtration rate, free water clearance and rate of urine production for up to 60 min. Doses greater than 1·0 ng/kg body weight induced a 'glomerular diuresis', i.e. increased rates of urine production, glomerular filtration and free water clearance for 40–60 min. Neither the diuretic nor the antidiuretic doses produce changes in urinary composition, and no obvious direct tubular actions of the peptide were found. Arterial blood pressure, measured in the dorsal aorta, increased with some of the diuretic doses, whilst the lower doses (less than 10 ng/kg body weight) had little or no cardiovascular actions. The mechanisms involved in these dose—response characteristics are discussed with particular regard to the renal function of lower vertebrates. It is suggested that arginine vasotocin plays a primary or secondary role in the modulation of 'glomerular intermittency'.

The Effect of Indomethacin on Vasopressin-Induced Antidiuresis in Man

1981 ◽  
Vol 61 (4) ◽  
pp. 493-495 ◽  
Author(s):  
P. L. Padfield ◽  
R. J. Grekin
Keyword(s):  
Weight Gain ◽  
Healthy Volunteer ◽  
Creatinine Clearance ◽  
Serum Potassium ◽  
Free Water ◽  
Free Water Clearance ◽  
Renal Response ◽  
Prostaglandin Production ◽  
Endogenous Prostaglandins ◽  
Water Clearance

1. The effect of 3 days' treatment with indomethacin on the renal response to infused vasopressin was assessed in eight healthy volunteer subjects. 2. Indomethacin produced significant weight gain and an increase in serum potassium without a change in creatinine clearance. 3. Although indomethacin reduced maximum free water clearance in five subjects, the antidiuresis produced by an incremental infusion of physiological amounts of vasopressin was no different whether indomethacin had been taken or not. 4. Indomethacin, in the dose we have used, is known to reduce prostaglandin production and we therefore conclude that endogenous prostaglandins do not inhibit the effect of physiological amounts of vasopressin on water clearance, which makes it unlikely that prostaglandins are important in the day-to-day modulation of the response to vasopressin.

Cooperative mechanisms of acute antidiuretic response to bendroflumethiazide in rats with lithium-induced nephrogenic diabetes insipidus

2010 ◽  
Vol 88 (12) ◽  
pp. 1191-1201 ◽  
Author(s):  
S. Mostafa Shid Moosavi ◽  
Masoud Haghani
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Urine Volume ◽  
Free Water ◽  
Urine Flow ◽  
Water Reabsorption ◽  
Free Water Clearance ◽  
Urinary Osmolality ◽  
Antidiuretic Effect ◽  
Water Clearance

The exact mechanism underlying thiazides-induced paradoxical antidiuresis in diabetes insipidus is still elusive, but it has been hypothesized that it is exerted either via Na+-depletion activating volume-homeostatic reflexes to decrease distal delivery, or direct stimulation of distal water reabsorption. This study examined how these two proposed mechanisms actually cooperate to induce an acute bendroflumethiazide (BFTZ)-antidiuretic effect in nephrogenic diabetes insipidus (NDI). Anaesthetized rats with lithium (Li)-induced NDI were prepared in order to measure their renal functional parameters, and in some of them, bilateral renal denervation (DNX) was induced. After a 30 min control clearance period, we infused either BFTZ into 2 groups, NDI+BFTZ and NDI/DNX+BFTZ, or its vehicle into a NDI+V group, and six 30 min experimental clearance periods were taken. During BFTZ infusion in the NDI+BFTZ group, transiently elevated Na+ excretion was associated with rapidly increased urinary osmolality and decreased free water clearance, but Li clearance and urine flow declined in the later periods. However, in the NDI/DNX+BFTZ group, there was persistently elevated Na+ excretion with unchanged Li clearance and urine flow during the experimental period, while alterations in free water clearance and urinary osmolality resembled those in the NDI+BFTZ group. In conclusion, BFTZ initially exerted two direct effects of natriuresis–diuresis and stimulating free water reabsorption at the distal nephron in NDI, which together elevated Na+ excretion and urinary osmolality but kept the urine volume unchanged in the first hour. Thereafter, the resultant sodium depletion led to the activation of neural reflexes that reduced distal fluid delivery to compensate for BFTZ-induced natriuresis–diuresis which, in cooperation with the direct distal BFTZ-antidiuretic effect, resulted in excretion of urine with a low volume, high osmolality, and normal sodium.

Nonoxidative glucose metabolism a prerequisite for formation of dilute urine

1982 ◽  
Vol 242 (5) ◽  
pp. F491-F498
Author(s):  
A. D. Baines ◽  
B. D. Ross
Keyword(s):  
Glucose Metabolism ◽  
Free Water ◽  
Glucose Production ◽  
Inhibitory Effect ◽  
Sodium Reabsorption ◽  
Diluting Segment ◽  
Free Water Clearance ◽  
Water Excretion ◽  
Total Sodium ◽  
Water Clearance

To examine links between norepinephrine- (NE) stimulated sodium transport and gluconeogenesis, we perfused isolated rat kidneys with 6% albumin, containing various combinations of glucose, alanine, pyruvate. and lactate and inhibitors of gluconeogenesis (0.1 mM mercaptopicolinate, MP) or glucose metabolism (0.2-0.5 mM 2-deoxyglucose, DG). Inulin clearance, fractional potassium reabsorption, total sodium reabsorption, and free water clearance were higher in kidneys perfused with 5 mM glucose plus 2 mM alanine than in kidneys perfused with either 10 mM lactate or 5 mM pyruvate. NE, added after 40 min of perfusion, decreased fractional sodium and potassium excretion in all experiments. In lactate- and/or pyruvate-perfused kidneys NE decreased fractional water excretion with little increase in free water clearance; free water formation was lowest in kidneys perfused with DG or MP. Glucose (5 mM) reversed the inhibitory effect of MP on free water clearance. In glucose-perfused kidneys NE did not decrease fractional water excretion, whereas free water clearance increased threefold. NE stimulated glucose production from pyruvate 2.4-fold and from lactate 1.6-fold. MP inhibited gluconeogenesis both in the basal state and after NE. We conclude that the formation of dilute urine requires nonoxidative glucose metabolism to maintain low water permeability in the diluting segment and a high peritubular glucose concentration that is ensured by gluconeogenesis in adjacent proximal tubules.

scholarly journals Impaired Urine Dilution Capability in HIV Stable Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Waldo H. Belloso ◽  
Mariana de Paz Sierra ◽  
Matilde Navarro ◽  
Marisa L. Sanchez ◽  
Ariel G. Perelsztein ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Proximal Tubule ◽  
Free Water ◽  
Antiretroviral Drugs ◽  
Control Group ◽  
Sodium Reabsorption ◽  
Thick Ascending Limb ◽  
Free Water Clearance ◽  
Proximal Tubular Function ◽  
Water Clearance

Renal disease is a well-recognized complication among patients with HIV infection. Viral infection itself and the use of some antiretroviral drugs contribute to this condition. The thick ascending limb of Henle’s loop (TALH) is the tubule segment where free water clearance is generated, determining along with glomerular filtration rate the kidney’s ability to dilute urine.Objective. We analyzed the function of the proximal tubule and TALH in patients with HIV infection receiving or not tenofovir-containing antiretroviral treatment in comparison with healthy seronegative controls, by applying a tubular physiological test, hyposaline infusion test (Chaimowitz’ test).Material & Methods. Chaimowitz’ test was performed on 20 HIV positive volunteers who had normal renal functional parameters. The control group included 10 healthy volunteers.Results. After the test, both HIV groups had a significant reduction of serum sodium and osmolarity compared with the control group. Free water clearance was lower and urine osmolarity was higher in both HIV+ groups. Proximal tubular function was normal in both studied groups.Conclusion. The present study documented that proximal tubule sodium reabsorption was preserved while free water clearance and maximal urine dilution capability were reduced in stable HIV patients treated or not with tenofovir.

Bicarbonate and sodium reabsorption by the isolated perfused kidney

1975 ◽  
Vol 228 (5) ◽  
pp. 1525-1530 ◽  
Author(s):  
A Besarab ◽  
P Silva ◽  
B Ross ◽  
FH Epstein
Keyword(s):  
Rat Kidney ◽  
Large Fraction ◽  
Free Water ◽  
Sodium Reabsorption ◽  
Renal Tubules ◽  
Free Water Clearance ◽  
Isolated Perfused Kidney ◽  
Bicarbonate Reabsorption ◽  
Perfused Kidney ◽  
Water Clearance

The role of bicarbonate reabsorption and of transtubular chloride gradients in the bulk reabsorption of sodium and water by renal tubules can be tested in the isolated perfused kidney by perfusing with a medium from which bicarbonate has been omitted. Perfusion of the isolated rat kidney with an artificial medium in which bicarbonate is replaced by chloride results in a fall in fractional reabsorption of sodium from 97 to 84%. Stepwise restoration of bicarbonate concentration in the perfusion medium to 25 meq/liter is associated with a parallel recovery of sodium reabsorption to control levels. Inhibition of bicarbonate reabsorption with acetazolamide produces a slightly smaller reduction in sodium reabsorption (97-89%), an effect not seen in the absence of bicarbonate. Acetazolamide greatly increases phosphate excretion and free water clearance in a way consistent with suppression of proximal tubular reabsorption. By contrast, simple omission of bicarbonate from the perfusing medium does not alter phosphaturia or free water clearance. Reabsorption of bicarbonate appears to account for a fraction of sodium reabsorption roughly equivalent to the proportion of sodium associated stoichiometrically with bicarbonate in the glomerule filtrate. The data do not support the hypothesis that the development of a transtubular chloride gradient is critically important for the reabsorption of a large fraction of the glomerular filtrate.

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