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

Chen, Yung‐Chang; Cadnapaphornchai, Melissa A.; Yang, Jianhui; Summer, Sandra N.; Falk, Sandor; Li, Chunling; Wang, Weidong; Schrier, Robert W.

doi:10.1152/ajprenal.00384.2004

Cited by 51 publications

(41 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Additionally, the impaired cardiac function that often occurs with advanced myxedema can lead to an elevation in plasma AVP levels, and in experimental hypothyroidism, the impaired response to an acute water load was reversed by a V 2 R antagonist. 32 Whether hyponatremia develops at any stage of disease progression depends on the relative balance between water intake and excretory capacity; since maximal solute-free water clearance decreases as these defects become more pronounced, the incidence of hyponatremia increases as the severity of the underlying hypothyroidism worsens.…”

Section: Nephrogenic Syndrome Of Inappropriate Antidiuresismentioning

confidence: 99%

Hyponatremia Treatment Guidelines 2007: Expert Panel Recommendations

Verbalis

Goldsmith

Greenberg

et al. 2007

The American Journal of Medicine

Self Cite

523

498

View full text Add to dashboard Cite

Although hyponatremia is a common, usually mild, and relatively asymptomatic disorder of electrolytes, acute severe hyponatremia can cause substantial morbidity and mortality, particularly in patients with concomitant disease. In addition, overly rapid correction of chronic hyponatremia can cause severe neurologic deficits and death, and optimal treatment strategies for such cases are not established. Hyponatremia is the most common disorder of electrolytes encountered in clinical practice, occurring in up to 15% to 30% of both acutely and chronically hospitalized patients. 1 Although most cases are mild and relatively asymptomatic, hyponatremia is important clinically because: (1) acute severe hyponatremia can cause substantial morbidity and mortality; (2) mortality is higher in patients with hyponatremia who have a wide range of underlying diseases; and (3) overly rapid correction of chronic hyponatremia can cause severe neurologic deficits and death.Despite knowledge of hyponatremia since the mid-20th century, this common disorder remains incompletely understood in many basic areas because of its association with a plethora of underlying disease states, and its multiple etiologies with differing pathophysiologic mechanisms. 2 Optimal treatment strategies have not been well defined, both for these reasons and because of marked differences in symptomatology and clinical outcomes based on the acuteness or chronicity of the hyponatremia. 3 Vasopressin receptor antagonists have long been anticipated as a more effective method to treat hyponatremia by virtue of their unique aquaretic effect to selectively increase solute-free water excretion by the kidneys. 4 The recent approval of the first such agent, conivaptan, for clinical use by the US Food and Drug Administration (FDA) heralds the beginning of a new era in the management of hyponatremic disorders. However, effective therapy with these agents will require intelligent guidelines for their use. To this end, a panel of experts in hyponatremia convened to review current therapies for hyponatremia and to evaluate the situations in which aquaretic agents should be considered as alternatives or supplements to accepted current therapies. This review is a summary of the conclusions of this panel.

show abstract

Section: Nephrogenic Syndrome Of Inappropriate Antidiuresismentioning

confidence: 99%

Hyponatremia Treatment Guidelines 2007: Expert Panel Recommendations

Verbalis

Goldsmith

Greenberg

et al. 2007

The American Journal of Medicine

Self Cite

523

498

View full text Add to dashboard Cite

show abstract

“…In this rat model of hypothyroidism the increase in plasma AVP was associated with upregulation of AQP2. Moreover, a V2 receptor antagonist has been shown in this rat model of hypothyroidism to reverse the increased AQP2 and the impaired response to an acute water load (Figure 4) (44). The hypothyroid rats also demonstrated a diminution in maximal urinary concentration which was associated with a defect in the counter-current concentrating mechanism (45).…”

Section: Hypo-and Hyperthyroidismmentioning

confidence: 77%

“…Advanced hypothyroidism may be associated with a decrease in blood pressure secondary to diminished myocardial contractability and heart rate. These hemodynamics are mimicked in hypothyroid rats and are reversed with thyroxin replacement (44). These impaired systemic hemodynamics would be expected to activate baroreceptor-mediated, non-osmotic AVP release and indeed this is the case.…”

Section: Hypo-and Hyperthyroidismmentioning

confidence: 96%

See 1 more Smart Citation

Vasopressin and Aquaporin 2 in Clinical Disorders of Water Homeostasis

Schrier

2008

Seminars in Nephrology

Self Cite

View full text Add to dashboard Cite

The cloning of the V2 vasopressin receptor was a major advance in understanding the mechanisms involved in regulation of solute-free water excretion by arginine vasopressin (AVP) (1). Subsequently, mutations of the V2 receptor gene were found to account for approximately 85% of cases of congenital nephrogenic diabetes insipidus (2). The mechanisms whereby AVP activates the V2 receptor on the basolateral membrane of the principal cells of the collecting duct and leads to increased water permeability of the apical membrane were, however, quite perplexing. The water transport across the bilipid apical membrane of the principal cells was too fast to be due to diffusion alone. Thus, the shuttle hypothesis was proposed whereby theoretical water channels would be moved from the cytoplasm to the apical membrane of the principal cells by AVP (3). The discovery of the first water channel, aquaporin 1 (AQP1), by Agre and associates led to great excitement in the biomedical community and the awarding of the Nobel Prize in Chemistry in 2003 to Peter Agre (4). Subsequently, aquaporin 2 (AQP2) was identified by Sasaki et al. in the principal cells of the collecting duct (5). Further investigations have demonstrated that AVP is the major regulator of the AQP2 water channels (6). Activation of the V2 receptor on the principal cells of the collecting duct by AVP is associated with a cascade of events involving adenylyl cyclase-mediated cyclic AMP (Figure 1) (7) which leads to both short term and long term regulation of AQP2 (8,9). The short term regulation of AVP involves shuttling the AQP2 containing vesicles from the cytoplasm to the apical membrane. With suppression of vasopressin these apical AQP2 water channels then undergo endocytosis into the cytoplasm (3). The 5' flanking region of the AQP2 gene has a cyclic AMP response element which is involved in the long term upregulation of AQP2 protein expression by AVP (9).The discovery of non-peptide antagonists to the V2 receptor have added yet another important dimension to the understanding of total body water homeostasis (10). These V2 receptor antagonists are agents that specifically block the action of AVP in humans. The several V2 receptor antagonists presently involved in clinical studies are shown in Table 1 (11). In contrast to diuretics, which enhance urine water and electrolyte excretion, the V2 receptor antagonists increase electrolyte-free water excretion.A relative excess of total body water to cation concentration leads to hyponatremia in many clinical circumstances. In fact, hyponatremia is the most frequent electrolyte disturbance in hospitalized patients (12). V2 receptor antagonists have substantial clinical implications, since the majority of the hyponatremic states are due to the non-osmotic release of AVP (13). These V2 receptor antagonists have also been important vehicles to understand several waterPublisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers

show abstract

“…The increase in ADH levels has been mainly attributed to the hypothyroidism-induced decrease in cardiac output, which stimulates the carotid sinus baroreceptors and induces the release of ADH (11,12,13,14). Thus, hyponatremia in most of hypothyroid patients is the result of the inability to suppress maximally the secretion of ADH, which results in reduced water excretion (3,15). Indeed, it has been shown that the impaired water excretion in hypothyroidism is mediated through the upregulation of ADH-induced acquaporin-2 expression in the collecting tubules (15).…”

Section: Possible Mechanisms Of Hyponatremia In Patients With Hypothymentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Hypothyroidism-associated hyponatremia: mechanisms, implications and treatment

Liamis

Filippatos

Liontos

et al. 2017

European Journal of Endocrinology

View full text Add to dashboard Cite

Background: Patients with moderate to severe hypothyroidism and mainly patients with myxedema may exhibit reduced sodium levels (<135 mmol/L). Summary: The aim of this short review is the presentation of the mechanisms of hyponatremia and of the available data regarding its implications and treatment in patients with hypothyroidism. Hypothyroidism is one of the causes of hyponatremia, thus thyroid-stimulating hormone determination is mandatory during the evaluation of patients with reduced serum sodium levels. The main mechanism for the development of hyponatremia in patients with chronic hypothyroidism is the decreased capacity of free water excretion due to elevated antidiuretic hormone levels, which are mainly attributed to the hypothyroidism-induced decrease in cardiac output. However, recent data suggest that the hypothyroidism-induced hyponatremia is rather rare and probably occurs only in severe hypothyroidism and myxedema. Other possible causes and superimposed factors of hyponatremia (e.g. drugs, infections, adrenal insufficiency) should be considered in patients with mild/moderate hypothyroidism. Treatment of hypothyroidism and fluid restriction are usually adequate for the management of mild hyponatremia in patients with hypothyroidism. Patients with possible hyponatremic encephalopathy should be urgently treated according to current guidelines. Conclusions: Severe hypothyroidism may be the cause of hyponatremia. All hypothyroid patients with low serum sodium levels should be evaluated for other causes and superimposed factors of hyponatremia and treated accordingly.

show abstract

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

Cited by 51 publications

References 24 publications

Hyponatremia Treatment Guidelines 2007: Expert Panel Recommendations

Hyponatremia Treatment Guidelines 2007: Expert Panel Recommendations

Vasopressin and Aquaporin 2 in Clinical Disorders of Water Homeostasis

MANAGEMENT OF ENDOCRINE DISEASE: Hypothyroidism-associated hyponatremia: mechanisms, implications and treatment

Contact Info

Product

Resources

About