Thiazide induces water absorption in the inner  medullary collecting duct of normal and Brattleboro rats

Cesar, Katia R.; Magaldi, Antonio J.

doi:10.1152/ajprenal.1999.277.5.f756

Cited by 39 publications

(39 citation statements)

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“…Therefore, the Li-induced AQP2 downregulation was partially (from 20 to 40% of normal controls) reversed by chronic HCTZ treatment. Recently, an in vitro microperfusion study performed by Cesar and Magaldi (11) showed that HCTZ increased osmotic and diffusional water permeabilities in inner medullary collecting duct from normal rats (in the absence of vasopressin) and from Brattleboro rats. Our results suggest that the increase in water permeability induced by HCTZ in NDI should not be limited to the inner medullary collecting duct because our AQP2 immunohistochemistry in cortex showed the similar pattern to that in inner medulla (Figure 3).…”

Section: Hctz Treatment Partially Reverses Li-induced Aqp2 Downregulamentioning

confidence: 99%

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Antidiuretic Effect of Hydrochlorothiazide in Lithium-Induced Nephrogenic Diabetes Insipidus Is Associated with Upregulation of Aquaporin-2, Na-Cl Co-transporter, and Epithelial Sodium Channel

Kim

Lee²,

Oh³

et al. 2004

Journal of the American Society of Nephrology

133

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Abstract. Thiazides have been used in patients with nephrogenic diabetes insipidus (NDI) to decrease urine volume, but the mechanism by which it produces the paradoxic antidiuretic effect remains unclear. Previous studies have reported that downregulation of aquaporin-2 (AQP2) is important for the development of lithium-induced (Li-induced) polyuria and that hydrochlorothiazide (HCTZ) increases renal papillary osmolality and Na ϩ concentration in Brattleboro rats. For elucidating the molecular basis of the antidiuretic action of HCTZ in diabetes insipidus, whether administration of HCTZ may affect the expression of AQP2 and major renal Na ϩ transporters in Li-induced NDI rats was investigated, using semiquantitative immunoblotting and immunohistochemistry. After feeding male Sprague-Dawley rats Li chloride-containing rat diet for 4 wk, HCTZ or vehicle was infused subcutaneously via osmotic minipump. Urine output was significantly decreased by HCTZ treatment, whereas it was not changed in vehicle-treated rats. Urine osmolality was also higher in HCTZ-treated rats than in vehicle-treated rats. Semiquantitative immunoblotting using whole-kidney homogenates revealed that HCTZ treatment caused a significant partial recovery in AQP2 abundance from Li-induced downregulation. AQP2 immunohistochemistry showed compatible findings with the immunoblot results in both cortex and medulla. The abundances of thiazide-sensitive NaCl co-transporter and ␣-epithelial sodium channel were increased by HCTZ treatment. Notably, HCTZ treatment induced a shift in molecular weight of ␥-epithelial sodium channel from 85 to 70 kD, consistent with previously demonstrated aldosterone stimulation. The upregulation of AQP2 and distal renal Na ϩ transporters in response to HCTZ treatment may account for the antidiuretic action of HCTZ in NDI.In nephrogenic diabetes insipidus (NDI), the kidney is unable to concentrate urine despite normal or elevated concentrations of the antidiuretic hormone arginine vasopressin. The acquired form of NDI is much more common than the congenital form, which has mutations either in the vasopressin V 2 receptor gene or in the aquaporin-2 (AQP2) gene (1). Lithium (Li) treatment (2), hypokalemia (3), and ureteral obstruction (4) are three common causes of acquired NDI, and all have been associated with downregulation of AQP2 (2-4).One of the recommended regimens for the treatment of NDI is low-sodium diet coupled with thiazides, although amiloride is preferably used to mitigate Li-induced polyuria in humans because of its blunting the inhibitory effect of Li on water transport in the collecting duct (5). Thiazide diuretics paradoxically decrease urine volume and increase urine osmolality presumably by producing a mild sodium depletion (6). The widely accepted hypothesis suggests that thiazide-induced sodium depletion causes a reduction in distal delivery associated with enhanced fractional water reabsorption in the collecting duct (6,7). However, the mechanism by which thiazide diuretics produce their paradoxic antidi...

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Section: Hctz Treatment Partially Reverses Li-induced Aqp2 Downregulamentioning

confidence: 99%

“…In addition, the possibility that thiazide diuretics can directly affect water permeability in the collecting duct epithelium was suggested (10), and a recent in vitro microperfusion study reported that HCTZ enhanced water absorption in inner medullary collecting duct from normal rats and from Brattleboro rats (11).…”

mentioning

confidence: 99%

Antidiuretic Effect of Hydrochlorothiazide in Lithium-Induced Nephrogenic Diabetes Insipidus Is Associated with Upregulation of Aquaporin-2, Na-Cl Co-transporter, and Epithelial Sodium Channel

Kim

Lee²,

Oh³

et al. 2004

Journal of the American Society of Nephrology

133

View full text Add to dashboard Cite

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“…Interestingly, in these experiments, addition of prostaglandins diminished the effect of thiazides, possibly explaining why prostaglandin synthesis inhibitors (e.g. indomethacin) augment the effect of thiazides in DI (17).…”

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confidence: 81%

“…Furthermore, functional studies by Shirley et al (12) and Gronbeck et al (16) suggested that water reabsorption downstream of the proximal tubule must also contribute to the antidiuresis seen after prolonged thiazide treatment of central DI. Cesar and Magaldi reported that hydrochlorothiazide (HCTZ) is able to directly increase the water permeability in inner medullary collecting ducts isolated from normal or Brattleboro rats and perfused in vitro (17). Interestingly, in these experiments, addition of prostaglandins diminished the effect of thiazides, possibly explaining why prostaglandin synthesis inhibitors (e.g.…”

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confidence: 98%

Paradoxical Antidiuretic Effect of Thiazides in Diabetes Insipidus

Loffing¹

2004

Journal of the American Society of Nephrology

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Diabetes insipidus (DI) is a temporary or chronic disorder characterized by the excretion of excessive quantities of very dilute, but otherwise normal urine. The disease results either from impaired synthesis and secretion of antidiuretic hormone (ADH, vasopressin) by the hypothalamus and posterior pituitary, respectively (central DI), or from an unresponsiveness of the kidneys to the hormone itself (nephrogenic DI) (1-3). The renal water transport defect is located in the collecting system (i.e. the connecting tubule -CNT and the collecting duct -CD) in which vasopressin normally controls the expression and cell surface targeting of the apical water channel aquaporin-2 (AQP2) (4). The CNT and CD are also the site of amiloridesensitive sodium reabsorption via the epithelial sodium channel (ENaC) (5). Sodium transport across ENaC may osmotically drive transepithelial water reabsorption. Consistently, both AQP2 and ENaC are regulated by vasopressin via V2-receptordependent cAMP production (4,5). While exogenous application of vasopressin efficiently corrects the reduced AQP2 expression and the urinary concentration defect in central DI (4), the treatment of nephrogenic DI is usually less obvious and may include different approaches such as dietary sodium restriction, prostaglandin synthesis inhibitors, potassium-sparing diuretics and/or thiazide diuretics (3,6). The use of diuretics for the treatment of a polyuric disease appears paradoxical, but the beneficial effect of thiazides has now been proven for more than 45 yr. In 1959, Crawford and Kennedy showed in a seminal paper that thiazides reduce polyuria and increase urine osmolality in DI (7). Since then, thiazides have become an important component in the therapeutic repertoire for treatment of DI. Nevertheless, the precise mechanisms by which thiazide diuretics elicit their paradoxical anti-diuretic effect in DI are still largely elusive.Thiazide diuretics inhibit the NaCl co-transporter (NCC/ TSC) in the renal distal convoluted tubule (DCT) (8). The DCT is water impermeable and considered to be part of the diluting segment (8). Therefore, the water-preserving effect of thiazides is unlikely related to a direct effect on the DCT. In fact, the most widely accepted hypothesis suggests that the antidiuretic action of thiazides is secondary to increased renal sodium excretion (1,2,6). The renal sodium loss causes extracellular volume contraction leading to lowered GFR and increased proximal tubular sodium and water reabsorption. Hence, less water and solutes are delivered to the distal tubule and collecting duct and are lost as urine (1,2,6). Indeed, micropuncture and renal clearance studies on normal rats (9 -11) or rats with DI (12,13) support this hypothesis. However, there is also increasing evidence that sodium depletion and increased proximal water reabsorption does not solely account for the antidiuretic effect. Spannow et al. demonstrated that the replacement of renal sodium losses by a servo-controlled system does not prevent the acute antidiuretic effe...

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“…Thus, there is less delivery of fluid to the collecting duct, resulting in a lower urine output. However, some studies indicate that there may also be a more direct effect of thiazides to increase water permeability of collecting duct principal cells (30,76).…”

Section: Nephrogenic Diabetes Insipidusmentioning

confidence: 99%

New insights into the dynamic regulation of water and acid-base balance by renal epithelial cells

Brown

Bouley

Păunescu

et al. 2012

American Journal of Physiology-Cell Physiology

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Maintaining tight control over body fluid and acid-base homeostasis is essential for human health and is a major function of the kidney. The collecting duct is a mosaic of two cell populations that are highly specialized to perform these two distinct processes. The antidiuretic hormone vasopressin (VP) and its receptor, the V2R, play a central role in regulating the urinary concentrating mechanism by stimulating accumulation of the aquaporin 2 (AQP2) water channel in the apical membrane of collecting duct principal cells. This increases epithelial water permeability and allows osmotic water reabsorption to occur. An understanding of the basic cell biology/physiology of AQP2 regulation and trafficking has informed the development of new potential treatments for diseases such as nephrogenic diabetes insipidus, in which the VP/V2R/AQP2 signaling axis is defective. Tubule acidification due to the activation of intercalated cells is also critical to organ function, and defects lead to several pathological conditions in humans. Therefore, it is important to understand how these "professional" proton-secreting cells respond to environmental and cellular cues. Using epididymal proton-secreting cells as a model system, we identified the soluble adenylate cyclase (sAC) as a sensor that detects luminal bicarbonate and activates the vacuolar proton-pumping ATPase (V-ATPase) via cAMP to regulate tubular pH. Renal intercalated cells also express sAC and respond to cAMP by increasing proton secretion, supporting the hypothesis that sAC could function as a luminal sensor in renal tubules to regulate acid-base balance. This review summarizes recent advances in our understanding of these fundamental processes. aquaporin 2; vacuolar ATPase; intercalated cell; principal cell; kidney; epididymis IT HAS BEEN KNOWN FOR MANY years that the major functions of collecting duct principal cells and intercalated cells (Fig. 1) can be regulated by the recycling of aquaporin 2 (AQP2) and the vacuolar H ϩ -ATPase (V-ATPase), respectively, between cytoplasmic vesicles and the plasma membrane (1,26,28,40,54,67,85,142). A considerable amount of the earlier data illuminating these processes was generated using readily accessible model epithelial systems such as the toad urinary bladder (48,83,140) and the turtle bladder (3,127,128), in which cellular function and morphology could be correlated with measurements of water flux and acid-base transport. More recently, a variety of in vitro cell culture models have replaced the toad bladder as an experimental system for water channel trafficking and function. This review will show how cell cultures have provided novel and important information on aquaporin 2 trafficking that has been translatable to the in vivo situation and has allowed the development of strategies to bypass the vasopressin (VP)/vasopressin type 2 receptor (V2R) signaling axis that is defective in nephrogenic diabetes insipidus (NDI). We will go on to demonstrate how the epididymis and vas deferens (from the male reproductive tract) ha...

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Thiazide induces water absorption in the inner medullary collecting duct of normal and Brattleboro rats

Cited by 39 publications

References 32 publications

Antidiuretic Effect of Hydrochlorothiazide in Lithium-Induced Nephrogenic Diabetes Insipidus Is Associated with Upregulation of Aquaporin-2, Na-Cl Co-transporter, and Epithelial Sodium Channel

Antidiuretic Effect of Hydrochlorothiazide in Lithium-Induced Nephrogenic Diabetes Insipidus Is Associated with Upregulation of Aquaporin-2, Na-Cl Co-transporter, and Epithelial Sodium Channel

Paradoxical Antidiuretic Effect of Thiazides in Diabetes Insipidus

New insights into the dynamic regulation of water and acid-base balance by renal epithelial cells

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