Recent Advances in the Understanding of Water Metabolism in Heart Failure

Schrier, Robert W.; Martin, Pierre‐Yves

doi:10.1007/978-1-4615-4871-3_53

Cited by 41 publications

(21 citation statements)

References 63 publications

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“…The increased reabsorption of sodium in the proximal tubule of the nephron, leading to a decreased distal sodium delivery, results in an inability of the nephron to generate free water. In addition, the nonosmotic release of vasopressin through osmoreceptor and nonosmoreceptor pathways 18,19 further impairs free water clearance, ultimately resulting in hyponatremia. In the management of patients with cirrhosis and severe hyponatremia, the usual practice is to expand the intravascular volume of these patients in an attempt to counteract the hemodynamic abnormalities; or to correct the causes of systemic vasodilatation such as infection; or to eliminate the causes of dehydration such as diuretic therapy or excessive diarrhea from over-zealous use of lactulose.…”

Section: Discussionmentioning

confidence: 99%

A vasopressin receptor antagonist (VPA-985) improves serum sodium concentration in patients with hyponatremia: A multicenter, randomized, placebo-controlled trial

et al. 2003

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for The North American VPA-985 Study Group Hyponatremia in advanced cirrhosis and ascites or congestive heart failure (CHF) is the result of an inappropriate increase in vasopressin secretion, which acts through activation of specific V 2 receptors in the distal renal nephron to increase water reabsorption. This study investigates the efficacy and safety of 3 different doses of the V 2 receptor antagonist, VPA-985, in correcting hyponatremia over a 7-day inpatient study period. Forty-four hospitalized patients (33 patients with cirrhosis, 6 with CHF, and 5 with syndrome of inappropriate antidiuretic hormone (SIADH) were studied on a constant sodium intake, with VPA doses of 25, 125, and 250 mg twice daily or placebo. Serum sodium measurements were repeated after every daily dose, and the next dose withheld for excessive serum sodium rises. Fluid intake was adjusted according to previous 24-hour urinary outputs. Adverse events were based on clinical signs of dehydration or encephalopathy. VPA-985 produced a significant overall aquaretic response compared with placebo, with significant dose related increases in free water clearance (P < .05) and serum sodium (P < .05), without significant changes in orthostatic blood pressure or serum creatinine levels. Five patients (50%) on 250 mg twice daily had to have medication withheld on multiple occasions. End-of-study plasma vasopressin levels increased significantly in the 2 larger dose groups. In conclusion, VPA-985 appears effective and safe in appropriate doses in correcting abnormal renal water handling and hyponatremia in conditions associated with water retention. Higher doses of VPA-985 may produce significant dehydration and will require close monitoring with their use. (HEPATOLOGY 2003;37:182-191.)See Editorial on Page 13 P atients with advanced cirrhosis and ascites or with congestive heart failure (CHF) have a disturbance in water metabolism, resulting in decreased renal free water excretion and dilutional hyponatremia. 1 The presence of hyponatremia in hospitalized patients with alcoholic cirrhosis or CHF is associated with a significantly increased mortality. 2,3 The inability of these patients to excrete an appropriate amount of free water is related to many factors, the most important of which is the nonosmotic stimulation of vasopressin release. [4][5][6] Plasma vasopressin levels are increased despite low plasma osmolality, 7 reflecting the resetting of the osmostat to a lower osmolar threshold for vasopressin suppression. 8 Vasopressin exerts its effects on water metabolism through the activation of specific V 2 receptors, which are expressed on the cells of the ascending limb of the loop of Henle and on the cells of the collecting duct of the nephron. 9 In the collecting duct, the activation of the V 2 receptor increases water reabsorption directly through the insertion of water channels into the otherwise water-impermeable collecting duct cells. 10 V 2 receptor antagonists, by competitive binding to the V 2 receptor, can displace vasopressin and, the...

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Section: Discussionmentioning

confidence: 99%

A vasopressin receptor antagonist (VPA-985) improves serum sodium concentration in patients with hyponatremia: A multicenter, randomized, placebo-controlled trial

et al. 2003

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“…The increase in AVP levels results in impaired excretion of free water in patients with heart failure due to an increase in the number of AQP channels in the collecting duct (8). This results not only in abnormal water retention but also in hyponatremia (11). Water retention has detrimental effect in patients with heart failure because it leads to increased congestion, while hyponatremia is associated with increased mortality (12).…”

Section: Therapeutic Potential Of Vasopressin-receptor Antagonists Inmentioning

confidence: 99%

Therapeutic Potential of Vasopressin-Receptor Antagonists in Heart Failure

2014

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Abstract. Arginine vasopressin (AVP) is a 9-amino acid peptide that is secreted from the posterior pituitary in response to high plasma osmolality and hypotension. AVP has important roles in circulatory and water homoeostasis, which are mediated by oxytocin receptors and by AVP receptor subtypes: V 1a (mainly vascular), V 1b (pituitary), and V 2 (renal). Vaptans are orally and intravenously active nonpeptide vasopressin-receptor antagonists. Recently, subtype-selective nonpeptide vasopressin-receptor agonists have been developed. A selective V 1a -receptor antagonist, relcovaptan, has shown initial positive results in the treatment of Raynaud's disease, dysmenorrhea, and tocolysis. A selective V 1b -receptor antagonist, nelivaptan, has beneficial effects in the treatment of psychiatric disorders. Selective V 2 -receptor antagonists including mozavaptan, lixivaptan, satavaptan, and tolvaptan induce highly hypotonic diuresis without substantially affecting the excretion of electrolytes. A nonselective V 1a /V 2 -receptor antagonist, conivaptan, is used in the treatment for euvolaemic or hypervolemic hyponatremia. Recent basic and clinical studies have shown that AVP-receptor antagonists, especially V 2 -receptor antagonists, may have therapeutic potential for heart failure. This review presents current information about AVP and its antagonists.

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“…The same is true for activation of the RAAS. 23,24 In fact, Lilly and associates 25 showed that hyponatremic patients had significantly increased plasma renin activity and norepinephrine and epinephrine levels compared with patients with normal serum sodium levels. Along those lines, hyonatremic patients had a significantly better outcome when treated with angiotensin-converting enzyme inhibitors than when treated with vasodilators (median survival, 232 vs 108 days).…”

Section: The Pathologic Role Of Vasopressin In Hfmentioning

confidence: 99%

“…26 In concert with other neurohormonal systems that are activated in HF, elevated AVP levels contribute to abnormal hemodynamics by increasing systemic vascular resistance, afterload, and pulmonary capillary wedge pressure. 23,24 Furthermore, prolonged exposure to high levels of AVP may contribute to vascular smooth muscle cell hypertrophy and hyperplasia as well as myocardial hypertrophy and adverse cardiac remodeling. 27 Excess AVP is also critically important in the pathogenesis of impaired free water excretion, which commonly complicates HF.…”

Section: The Pathologic Role Of Vasopressin In Hfmentioning

confidence: 99%

Hyponatremia in Heart Failure: The Role of Arginine Vasopressin and Its Antagonism

Rosner

Ronco

2010

Congestive Heart Failure

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Congest Heart Fail. 2010;16(4)(suppl 1):S7–S14. ©2010 Wiley Periodicals, Inc.Heart failure (HF) is associated with substantial cost, morbidity, and mortality. One of the common complications associated with HF, as well as with its treatment, is the development of hyponatremia. Hyponatremia is due to the nonosmotic release of arginine vasopressin (AVP) along with neurohormonal activation of the renin‐angiotensin‐aldosterone and sympathetic nervous systems. Hyponatremia in patients with HF is associated with poor outcomes and can limit the use of diuretic therapy. Given that AVP is the primary stimulus for the development of hyponatremia in these patients, therapies that target AVP action would seem a logical choice in the therapeutic regimen for HF. Drugs that antagonize the action of AVP at the vasopressin V2 receptor, which is primarily responsible for water resorption in the kidney, are now available and have been studied in patients with HF. These drugs (termed vaptans) have been associated with improvements in serum sodium concentration, urine output, body weight, and mental functioning but have shown no long‐term mortality benefit in patients with HF. The role of vaptans in the HF armament will require further studies that center on the proper timing and indications for their use as well as their cost‐efficacy.

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Recent Advances in the Understanding of Water Metabolism in Heart Failure

Cited by 41 publications

References 63 publications

A vasopressin receptor antagonist (VPA-985) improves serum sodium concentration in patients with hyponatremia: A multicenter, randomized, placebo-controlled trial

A vasopressin receptor antagonist (VPA-985) improves serum sodium concentration in patients with hyponatremia: A multicenter, randomized, placebo-controlled trial

Therapeutic Potential of Vasopressin-Receptor Antagonists in Heart Failure

Hyponatremia in Heart Failure: The Role of Arginine Vasopressin and Its Antagonism

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