Body Water Homeostasis

Abstract

T he discovery of the aquaporin-1 (AQP1) water channel by Agre and colleagues (1,2), which led to the Nobel Prize in 2003, has revolutionized the understanding of body fluid water regulation by the kidney. Moreover, the identification of other water channels in the kidney, namely AQP2, 3, and 4, along with urea and ion transporters, has allowed a much improved understanding of urinary dilution and concentration in health and disease at the cellular and molecular levels (3-8).The AQP have provided a pathway for water movement across cellular membranes that could not be explained by simple diffusion through the lipid bilayers of cell membranes. AQP1 has been found to be expressed constitutively on both the apical and the basolateral membranes of the proximal tubule and descending limb of Henle's loop. This water channel is not under control of vasopressin but is important in urinary concentration. Water efflux through these channels in the descending limb is an important factor in the countercurrent concentrating mechanism, and diminished maximal urinary osmolality has been shown in AQP1 knockout mice (9) and humans without the AQP1 gene (10).AQP2, 3, and 4 are expressed in the cortical and medullary collecting duct ( Figure 1) (11). AQP2 is found exclusively in the principal cells of the collecting tubule and collecting duct and is known to be regulated by arginine vasopressin (AVP). AQP3 and 4 are located on the basolateral membrane of the principal cells in the collecting duct. AQP3 knockout mice exhibit substantial polyuria secondary to vasopressin-resistant nephrogenic diabetes insipidus (NDI) (12). AQP3 is regulated by AVP. AQP4 predominates on the basolateral membrane of the inner medulla and is not regulated by AVP. AQP4 knockout mice also exhibit an NDI that is less severe than that observed in the AQP3 knockout mice (13). Whereas AQP3 and AQP4 constitute the exit channels for water movement across the basolateral membrane of the collecting duct, AQP2 is the water channel for water reabsorption across the apical membrane of the principal cells of the collecting duct. These transgenic mouse models of AQP deletion/mutation are of importance not only for kidney function but also for other epithelia (14).AVP regulates AQP2 in both an acute (short term) (15) and chronic (long term) manner (16,17). The short-term regulation by AVP involves trafficking of vesicles that contain AQP2 to the apical membrane with resultant increased water permeability. Suppression of plasma AVP reverses this exocytosis of AQP2, and the vesicles are retrieved from the membrane (endocytosis) into the cytoplasm. Both the short-and long-term regulation of AQP2 by AVP is initiated by activation of the V2 receptor on the basolateral membrane of the collecting duct. The binding of AVP to the V2 receptor, which is coupled to a guanine-nucleotide-binding protein Gs, results in activation of adenylyl cyclase. This results in an increase in intracellular cAMP concentration that mediates the activation of protein kinase A (PKA). Activated PKA p...

Downregulation of UT-A1/UT-A3 Is Associated with Urinary Concentrating Defect in Glucocorticoid-Excess State

“…Most important, the protein expression of AQP2 water channel in the principal cells of the collecting duct are vasopressin dependent and are therefore the primary regulator of renal water excretion. 9 In this study, however, the increased urine output of glucocorticoid excess was not associated with any alteration in AQP2 expression. Thus, the increased urine output could not be explained by alterations in renal AQP1, 2, or 3 water channels.…”

Hyponatremia Treatment Guidelines 2007: Expert Panel Recommendations

“…A spot urine [Na ϩ ] should be Ͻ30 mmol/L in patients with hypovolemic hyponatremia unless the kidney is the site of sodium loss. 9 When the clinical assessment is equivocal, a trial of volume expansion can be helpful in establishing the diagnosis, and will be therapeutic if volume depletion is the cause of the hyponatremia. After a 0.5 to 1 L infusion of isotonic (0.9%) NaCl, patients with hypovolemic hyponatremia will begin to correct their hyponatremia without developing signs of volume overload.…”

“…A spot urine [Na ϩ ] should be Ն30 mmol/L in most patients with euvolemic hyponatremia unless they have become secondarily sodium depleted. 9 When the clinical assessment of ECF volume is equivocal, or the urine [Na ϩ ] is Ͻ30 mmol/L, a trial of volume expansion with isotonic saline can be helpful to ascertain the correct diagnosis (see above under "Hypovolemic hyponatremia").…”

Les troubles de l’équilibre hydrosodé chez les patients hospitalisés

“…In addition, AVP is an adrenocorticotropic hormone (ACTH) secretagogue, thus AVP release may be stimulated secondary to increased release of ACTH, due to the lack of negative feedback from absent serum cortisol. 18 Similarly, aldosterone deficiency leads to sodium wasting and reductions in ECV stimulating AVP release.…”