Role of aquaporin-2 gene expression in hyponatremic rats with chronic vasopressin-induced antidiuresis

Saitô, Takako; Higashiyama, Minori; Nagasaka, Shoichiro; Sasaki, Sei; Saito, Toshikazu; Ishikawa, San‐e

doi:10.1046/j.1523-1755.2001.00965.x

Cited by 36 publications

(49 citation statements)

References 38 publications

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“…In agreement with results of others (30,44,45,60,73), our liquid diet/ dDAVP-treated control rats developed all the characteristics of SIADH. Due to increased AVP-mediated renal water uptake, they were hyponatremic (99 Ϯ 1 mM) and hypoosmotic (236 Ϯ 10 mosM), as untreated control rats held under similar conditions displayed plasma Na ϩ concentrations and osmolalities of 141 mmol/l and 283 mosM, respectively (32).…”

Section: Discussionsupporting

confidence: 93%

“…As anticipated based on previous studies (30,44,45,60,73), our control rats were hyponatremic and hypoosmotic [normal values: 141 Ϯ 1 and 283 Ϯ 5, respectively (32); Table 1]. Treatment with demeclocycline resulted in a significant reduction of hyponatremia and a nearly significant correction of the hypoosmolality (P ϭ 0.08).…”

Section: Effect Of Tetracycline Antibiotics On Aqp2 Abundance In Vitrosupporting

confidence: 78%

“…Total collagen abundance was assessed using picrosirius red labeling in control (A-C) and demeclocycline-treated (D-F) rats. 60,74). In line with the beneficial effects of demeclocycline on hyponatremic patients (17,51), demeclocycline increased the fractional excretion of water, resulting in increased urine volume, decreased urine osmolality, and attenuated hyponatremia.…”

Section: Discussionmentioning

confidence: 82%

“…Previously, it has been shown that in SIADH and SIADH models, free water excretion is higher and AQP2 abundance is lower than anticipated, considering the high blood AVP levels, a phenomenon called "vasopressin escape" (13). Vasopressin escape indicated that variables other than AVP, such as hypervolemia or hypotoniciy, influence AQP2 expression (7,22,34,60). Based on these data, it is to be expected that some vasopressin escape is present in our animals, meaning that AQP2 levels would have likely been higher without this escape.…”

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confidence: 99%

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Demeclocycline attenuates hyponatremia by reducing aquaporin-2 expression in the renal inner medulla

Kortenoeven

Sinke

Hadrup

et al. 2013

American Journal of Physiology-Renal Physiology

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Kortenoeven ML, Sinke AP, Hadrup N, Trimpert C, Wetzels JF, Fenton RA, Deen PM. Demeclocycline attenuates hyponatremia by reducing aquaporin-2 expression in the renal inner medulla. Am J Physiol Renal Physiol 305: F1705-F1718, 2013. First published October 23, 2013 doi:10.1152/ajprenal.00723.2012.-Binding of vasopressin to its type 2 receptor in renal collecting ducts induces cAMP signaling, transcription and translocation of aquaporin (AQP)2 water channels to the plasma membrane, and water reabsorption from the prourine. Demeclocycline is currently used to treat hyponatremia in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Demeclocycline's mechanism of action, which is poorly understood, is studied here. In mouse cortical collecting duct (mpkCCD) cells, which exhibit deamino-8-D-arginine vasopressin (dDAVP)-dependent expression of endogenous AQP2, demeclocycline decreased AQP2 abundance and gene transcription but not its protein stability. Demeclocycline did not affect vasopressin type 2 receptor localization but decreased dDAVP-induced cAMP generation and the abundance of adenylate cyclase 3 and 5/6. The addition of exogenous cAMP partially corrected the demeclocycline effect. As in patients, demeclocycline increased urine volume, decreased urine osmolality, and reverted hyponatremia in an SIADH rat model. AQP2 and adenylate cyclase 5/6 abundances were reduced in the inner medulla but increased in the cortex and outer medulla, in the absence of any sign of toxicity. In conclusion, our in vitro and in vivo data indicate that demeclocycline mainly attenuates hyponatremia in SIADH by reducing adenylate cyclase 5/6 expression and, consequently, cAMP generation, AQP2 gene transcription, and AQP2 abundance in the renal inner medulla, coinciding with a reduced vasopressin escape response in other collecting duct segments. aquaporin 2; collecting duct; demeclocycline; syndrome of inappropriate antidiuretic hormone secretion; vasopressin THE KIDNEY is the main organ for the regulation of water homeostasis. In states of hypernatremia or hypovolemia, the hormone arginine vasopressin (AVP) is released from the pituitary and binds to the vasopressin type 2 receptor (V2R), which is expressed in the basolateral membrane of renal collecting duct principal cells (48). Activated V2R increases intracellular cAMP levels via G s protein and adenylate cyclase (AC), which eventually leads to the activation of PKA and subsequent phosphorylation of aquaporin (AQP)2 water channels (19,29). This results in the redistribution of AQP2 from intracellular vesicles to the apical membrane (19,29,46,72). Driven by the transcellular osmotic gradient, water enters principal cells through AQP2 and exits cells through AQP3 or AQP4, which are located in the basolateral membrane, resulting in concentrated urine. In addition, AVP also increases the expression of AQP2 via the phosphorylation of cAMP-responsive element-binding protein, which binds and activates transcription via a cAMP-responsive element in the A...

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Section: Discussionsupporting

confidence: 93%

Section: Effect Of Tetracycline Antibiotics On Aqp2 Abundance In Vitrosupporting

confidence: 78%

Section: Discussionmentioning

confidence: 82%

mentioning

confidence: 99%

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Demeclocycline attenuates hyponatremia by reducing aquaporin-2 expression in the renal inner medulla

Kortenoeven

Sinke

Hadrup

et al. 2013

American Journal of Physiology-Renal Physiology

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“…In the acute phase, there is an excess of extracellular fluid due to increased water reabsorption, which leads to dilutional hyponatremia. In the steady state, the metabolism of both water and sodium is altered in order to reduce excessive water retention, thereby resulting in euvolemic hyponatremia (7,8). Tolvaptan is the best drug for treating hyponatremia in patients with SIADH (6) and is currently available in the United States and Europe, although unfortunately not in Japan as of yet.…”

Section: Discussionmentioning

confidence: 99%

Prompt Efficacy of Tolvaptan in Treating Hyponatremia of Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH) Closely Associated with Rupture of a Gastric Artery Aneurysm

et al. 2014

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A 78-year-old man with abdominal pain was diagnosed with a rupture of a gastric artery aneurysm. The serum Na level promptly decreased from 135 to 110 mmol/L within several days. Brain magnetic resonance angiography revealed severe vasoconstriction of the cerebral basilar artery and anterior cerebral artery. There was neither dehydration nor edema. The plasma arginine vasopressin level was 3.3 pg/mL, despite hypoosmolality. These findings indicated a diagnosis of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) derived from severe vasoconstriction of the cerebral arteries. The administration of 7.5 mg of tolvaptan rapidly increased the serum Na level from 123 to 138 mmol/L within the first 24 hours, thereafter continuously maintaining a normal level. Treatment with tolvaptan corrected the patient's dilutional hyponatremia.

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Vasopressin and the regulation of aquaporin-2

2013

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Water excretion is regulated in large part through the regulation of the osmotic water permeability of the renal collecting duct epithelium. The water permeability is controlled by vasopressin through regulation of the water channel, aquaporin-2 (AQP2). Two processes contribute: 1) regulation of AQP2 trafficking to the apical plasma membrane; and 2) regulation of the total amount of the AQP2 protein in the cells. Regulation of AQP2 abundance is defective in several water balance disorders including many polyuric disorders and the syndrome of inappropriate antidiuresis (SIADH). Here we review vasopressin signaling in the renal collecting duct that is relevant to the two modes of water permeability regulation.

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Role of aquaporin-2 gene expression in hyponatremic rats with chronic vasopressin-induced antidiuresis

Cited by 36 publications

References 38 publications

Demeclocycline attenuates hyponatremia by reducing aquaporin-2 expression in the renal inner medulla

Demeclocycline attenuates hyponatremia by reducing aquaporin-2 expression in the renal inner medulla

Prompt Efficacy of Tolvaptan in Treating Hyponatremia of Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH) Closely Associated with Rupture of a Gastric Artery Aneurysm

Vasopressin and the regulation of aquaporin-2

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