Effect of water deprivation and hypertonic saline infusion on urinary AQP2 excretion in healthy humans

Pedersen, Robert S.; Bentzen, Hans; Bech, Jesper N.; Pedersen, E. B.

doi:10.1152/ajprenal.2001.280.5.f860

Cited by 84 publications

(87 citation statements)

References 19 publications

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“…However, both u-AQP2 and u-ENaC b increased significantly just as p-AVP, p-ANP, and pulse rate. The amount of ENaC b in urine is supposed to reflect the activity of sodium transport via the ENaCs, just as u-AQP2 reflects the functional status of the AQP2 water channels (6). Our analyses showed that the assay has a satisfactory reliability.…”

Section: Discussionmentioning

confidence: 70%

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Direct effect of methylprednisolone on renal sodium and water transport via the principal cells in the kidney

Lauridsen

Vase²,

Bech³

et al. 2010

European Journal of Endocrinology

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Background: Glucocorticoids influence renal concentrating and diluting ability. We tested the hypothesis that methylprednisolone treatment increased renal water and sodium absorption by increased absorption via the aquaporin-2 (AQP2) water channels and the epithelial sodium channels (ENaCs) respectively. Methods: The effect of methylprednisolone was measured during fasting in a randomized, placebocontrolled, single-blinded cross-over study of 15 healthy humans. The subjects received a standardized diet on day 1, fasted on day 2, and received 500 mg methylprednisolone intravenously on day 3. The effect variables were urinary excretions of AQP2 (u-AQP2), urinary excretion of the b-fraction of the ENaC (u-ENaC b ), cAMP (u-cAMP), prostaglandin E 2 (u-PGE 2 ), free water clearance (C H 2 O ), and fractional excretion of sodium (FE Na ), and plasma vasopressin (p-AVP), angiotensin II (p-Ang II), aldosterone (p-Aldo), atrial natriuretic peptide (p-ANP), and brain natriuretic peptide (p-BNP). Results: Methylprednisolone treatment increased u-AQP2, u-ENaC b , and p-AVP significantly, but did not change u-cAMP, C H 2 O , and FE Na . P-ANP increased during methylprednisolone treatment, but after the increase in u-AQP2 and u-ENaC b . U-PGE 2 , p-Ang II, and p-BNP were unchanged. Heart rate increased and diastolic blood pressure fell. Conclusions: Methylprednisolone increased u-AQP2 and u-ENaC. Neither the AVP-cAMP axis nor changes in the renin-angiotensin-Aldo system, or the natriuretic peptide system seems to bear a causal relationship with the increase in either u-AQP2 or u-ENaC. Most probably, the effect is mediated via a direct effect of methylprednisolone on the principal cells. The lack of decrease in urinary output and sodium reabsorption most likely can be attributed to the diuretic and natriuretic properties of the increased secretion of ANP.

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Section: Discussionmentioning

confidence: 70%

“…The degree of water transport via AQP2 is reflected by the level of urinary excretion of AQP2 (u-AQP2) (6). Correspondingly, the sodium transport via ENaCs is supposed to be reflected by the level of urinary excretion of the b-fraction of ENaC (u-ENaC b ).…”

Section: Introductionmentioning

confidence: 99%

Direct effect of methylprednisolone on renal sodium and water transport via the principal cells in the kidney

Lauridsen

Vase²,

Bech³

et al. 2010

European Journal of Endocrinology

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“…As urinary AQP2 excretion is very low compared to the total AQP2 in the kidney (E3%), it may not reflect intrarenal changes in the protein. Nevertheless, a positive correlation has been found recently between the maximum changes in the urinary excretion of AQP2 and the maximum changes in plasma vasopressin in healthy subjects (Pedersen et al, 2001) (Figure 1b).…”

Section: Renal Consequences Of a High Level Of Vasopressin In A Healtmentioning

confidence: 70%

Mild dehydration, vasopressin and the kidney: animal and human studies

Bouby

Fernandes

2003

Eur J Clin Nutr

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Water balance depends essentially on fluid intake and urine excretion. Mild dehydration and the consequent hypertonicity of the extracellular fluid induce an increase in vasopressin secretion, thus stimulating urine concentrating processes and the feeling of thirst. The osmotic threshold for the release of vasopressin is lower than that for thirst and also shows appreciable individual variation. Sustained high levels of vasopressin and low hydration induce morphological and functional changes in the kidney. However, they could also be risk factors in several renal disorders, such as chronic renal failure, diabetic nephropathy and saltsensitive hypertension.

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“…94 Urinary AQP2 is a commonly used assessment of AQP2 membrane targeting because it has been shown to reflect the physiologic response to VP in the CD. 95 This suggests that prostanoid-induced AQP2 membrane targeting is also observed in humans, which increases the clinical relevance of these findings.…”

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confidence: 73%

Is There a Role for PGE2 in Urinary Concentration?

Olesen

Fenton

2013

Journal of the American Society of Nephrology

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Prostanoids are prominent, yet complex, components in the maintenance of body water homeostasis. Recent functional and molecular studies have revealed that the local lipid mediator PGE2 is involved both in water excretion and absorption. The biologic actions of PGE2 are exerted through four different G-protein-coupled receptors; designated EP1-4, which couple to separate intracellular signaling pathways. Here, we discuss new developments in our understanding of the actions of PGE2 that have been uncovered utilizing receptor specific agonists and antagonists, EP receptor and PG synthase knockout mice, polyuric animal models, and the new understanding of the molecular regulation of collecting duct water permeability. The role of PGE2 in urinary concentration comprises a variety of mechanisms, which are not fully understood and likely depend on which receptor is activated under a particular physiologic condition. EP3 and microsomal PG synthase type 1 play a role in decreasing collecting duct water permeability and increasing water excretion, whereas EP2 and EP4 can bypass vasopressin signaling and increase water reabsorption through two different intracellular signaling pathways. PGE2 has an intricate role in urinary concentration, and we now suggest how targeting specific prostanoid receptor signaling pathways could be exploited for the treatment of disorders in water balance. The neurohypophyseal hormone, vasopressin (VP), is a major regulator of renal water excretion, predominantly through the seven trans-membrane receptor (7TMR) V2R. It binds to Gas, inducing the cAMP second messenger system, resulting in increased NaCl absorption by the thick ascending limb and increased urea transport in the inner medullary collecting ducts (IMCDs). [1][2][3] In addition, VP induces accumulation of the water channel aquaporin-2 (AQP2) in the rate-limiting apical plasma membrane of collecting duct (CD) principal cells, 4 a process that involves a diverse range of post-translational modifications including phosphorylation of AQP2. 5 Thus, VP increases the osmotic gradient for water transport and the water permeability (Pf) of the CD simultaneously.In addition to systemic hormones, local regulatory factors play a role in the CD, of which PGE2 (Figure 1) is the focus of this review. 6-9 PGE2 has a diverse range of biologic actions elicited by four different 7TMRs. The renal localization of EP receptors and intracellular signaling pathways are diverse (Table 1). Here, we propose that urinary concentration does not rely exclusively on fluctuations in plasma VP concentrations, but that the locally derived lipid mediator, PGE2, plays an important role in regulating water excretion. PGE2 IN THE MODULATION OF URINARY CONCENTRATING MECHANISMSThe ability of PGE2 to modulate the effects of VP in the CD has been described in a range of experimental studies and discussed in previous reviews. [36][37][38][39] The present focus is on understanding the mechanisms for this effect, and on recent in vivo studies elucidating the role of P...

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Effect of water deprivation and hypertonic saline infusion on urinary AQP2 excretion in healthy humans

Cited by 84 publications

References 19 publications

Direct effect of methylprednisolone on renal sodium and water transport via the principal cells in the kidney

Direct effect of methylprednisolone on renal sodium and water transport via the principal cells in the kidney

Mild dehydration, vasopressin and the kidney: animal and human studies

Is There a Role for PGE2 in Urinary Concentration?

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