Urinary Concentrating Defect in Hypothyroid Rats

Cadnapaphornchai, Melissa A.; Kim, Yang-Wook; Gurevich, Andrey; Summer, Sandra N.; Falk, Sandor; Thurman, Joshua M.; Schrier, Robert W.

doi:10.1097/01.asn.0000053417.33945.63

Cited by 39 publications

(25 citation statements)

References 17 publications

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“…This was anticipated, as all rats received the same intake of powdered rat chow. Consistent with our previous studies in short-term hypothyroidism (2), no significant differences were noted in water intake, urine output, urine osmolality, dietary sodium intake, serum osmolality, serum creatinine concentration, 24-h creatinine clearance, or urea or osmolar clearance between the three study groups before oral water loading. Fractional excretion of sodium was significantly higher in HT than HTϩT.…”

Section: Resultssupporting

confidence: 91%

See 1 more Smart Citation

Nonosmotic release of vasopressin and renal aquaporins in impaired urinary dilution in hypothyroidism

Chen

Cadnapaphornchai²,

Yang³

et al. 2005

American Journal of Physiology-Renal Physiology

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-The purpose of this study was to examine protein expression of renal aquaporins (AQP) and ion transporters in hypothyroid (HT) rats in response to an oral water load compared with controls (CTL) and HT rats replaced with L-thyroxine (HTϩT). Hypothyroidism was induced by aminotriazole administration for 10 wk. Body weight, water intake, urine output, solute and urea excretion, and serum and urine osmolality were comparable among the three groups at the conclusion of the 10-wk treatment period. One hour after oral gavage of water (50 ml/kg body wt), HT rats demonstrated significantly less water excretion, higher minimal urinary osmolality, and decreased serum osmolality compared with CTL and HTϩT rats. Despite the hyposmolality, plasma vasopressin concentration was elevated in HT rats. These findings in HT rats were associated with an increase in protein abundance of renal cortex AQP1 and inner medulla AQP2. AQP3, AQP4, and the Na-K-2Cl cotransporter were also increased. Moreover, 1 h following the oral water load, HT rats demonstrated a significant increase in the membrane-to-vesicle fraction of AQP2 by Western blot analysis. The defect in urinary dilution in HT rats was reversed by the V 2 vasopressin antagonist OPC-31260. In conclusion, impaired urinary dilution in HT rats is primarily compatible with the nonosmotic release of vasopressin and increased protein expression of renal AQP2. The impairment of maximal solute-free water excretion in HT rats, however, appears also to involve diminished distal fluid delivery.water transport; solute-free water excretion; thyroid disease HYPOTHYROIDISM IS A COMMON clinical disorder that is associated with significant abnormalities in systemic and renal hemodynamics and renal handling of salt and water. Patients and experimental animals with hypothyroidism demonstrate impaired water excretion, failure to achieve maximal urinary dilution, and hyponatremia (4,6,15,20). Maximal solute-free water excretion is dependent on factors including 1) appropriate delivery of fluid to the diluting segments of the distal nephron, determined by glomerular filtration rate and proximal tubular fluid and sodium reabsorption; 2) ion reabsorption in water-impermeable segments of the nephron; 3) decreased secretion of arginine vasopressin (AVP) in response to serum hyposmolality; and 4) decreased collecting duct solute-free water reabsorption via aquaporin (AQP)-2 water channels in response to suppressed plasma AVP concentrations. Previous studies have suggested that dysregulation of each of these factors contributes to impaired urinary dilution in hypothyroidism (4,6,15,20). However, a comprehensive molecular analysis has not been undertaken. The goal of this study was to examine the molecular mechanisms contributing to impaired urinary dilution in hypothyroidism. METHODSAnimal model. The study protocol was approved by the University of Colorado Institutional Animal Care and Use Committee. Animals were housed individually in metabolic cages (Nalgene metabolic cages; Nalge, Rochester, NY) and w...

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Section: Resultssupporting

confidence: 91%

“…Toward the conclusion of the aminotriazole treatment period, echocardiography was performed in nine rats in each of the three study groups using a GE Vingmed System Five imaging tool for small rodents with a 10-MHz probe (2). The animals were anesthetized with ketamine (40 mg/kg body wt ip) and xylazine (5 mg/kg body wt ip).…”

Section: Methodsmentioning

confidence: 99%

Nonosmotic release of vasopressin and renal aquaporins in impaired urinary dilution in hypothyroidism

Chen

Cadnapaphornchai²,

Yang³

et al. 2005

American Journal of Physiology-Renal Physiology

Self Cite

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“…Of interest, a defect in maximal urinary concentration was observed at a somewhat less prolonged stage of experimental hypothyroidism (30). Maximal urinary osmolality with fluid deprivation was associated with decreased Na-K-2Cl expression and diminished medullary osmolality.…”

Section: Hypothyroidismmentioning

confidence: 97%

Body Water Homeostasis

Schrier¹

2006

Journal of the American Society of Nephrology

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173

110

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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...

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“…In severe hypothyroidism with myxedema, increased release of antidiuretic hormone (ADH) and decreased delivery to the diluting tubular segments caused by reduced CO and GFR led to hyponatremia (60). The urine concentrating ability is impaired in hypothyroid state due to decreased osmotic driving force in the collecting duct, to decrease response of vasopressin and to impaired water handling (61,62). In addition, Na + reabsorption through NHE and Na+ -Pi co-transporter activity are decreased in animals with hypothyroidism (63).…”

Section: Thyroid Disorders and Tubular Functionmentioning

confidence: 99%

The Thyroid and the Kidney: A Complex Interplay in Health and Disease

et al. 2014

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Thyroid hormones may directly affect the kidney and altered kidney function may also contribute to thyroid disorders. The renal manifestations of thyroid disorders are based on hemodynamic alterations or/and to direct effects of thyroid hormones. The renin-angiotensin system plays a crucial role in the cross-talk between the thyroid and the kidney. Hypothyroidism may be accompanied by an increase of serum creatinine and reduction of glomerular filtration rate (GFR), whereas hyperthyroidism may increase GFR. Treatment of thyroid disorders may lead to normalization of GFR. Primary and subclinical hypothyroidism and low triiodothyronine (T3) syndrome are common features in patients with chronic kidney disease (CKD). In addition low levels of thyroid hormones may predict a higher risk of cardiovascular and overall mortality in patients with end-stage renal disease. The causal nature of this correlation remains uncertain. In this review, special emphasis is given to the thyroid pathophysiology, its impact on kidney function and CKD and the interpretation of laboratorial findings of thyroid dysfunction in CKD.

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Urinary Concentrating Defect in Hypothyroid Rats

Cited by 39 publications

References 17 publications

Nonosmotic release of vasopressin and renal aquaporins in impaired urinary dilution in hypothyroidism

Nonosmotic release of vasopressin and renal aquaporins in impaired urinary dilution in hypothyroidism

Body Water Homeostasis

The Thyroid and the Kidney: A Complex Interplay in Health and Disease

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