Vasopressin receptor antagonism — a therapeutic option in heart failure and hypertension

Burrell, Louise M.; Risvanis, John; Johnston, Colin I.; Naitoh, Motoko; Balding, Leanne C.

doi:10.1111/j.1469-445x.2000.tb00031.x

Cited by 40 publications

(36 citation statements)

References 49 publications

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“…The antagonism of V 2 receptors induces the elimination of free-water (''aquaresis'') without depleting electrolytes or activating neurohormonal systems, common side effects of diuretic therapy [51]. Furthermore, the antagonism of V 1A /V 2 receptors provides aquaresis induced by the V 2 receptor stimulation and should suppress the deleterious cardiac effects caused by the activation of the V 1A receptor [49,52]. Experimental models and clinical trials have shown that AVP receptor antagonists represent a promising approach for the treatment of hyponatremia in HF [53,54].…”

Section: Treatment and Avp Antagonismmentioning

confidence: 98%

Significance of hyponatremia in heart failure

Bettari¹,

Fiuzat

Felker

et al. 2010

Heart Fail Rev

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Heart failure is one of the most common, costly, disabling and growing diseases (McMurray and Pfeffer in Lancet 365(9474):1877-1889, 2005). Hyponatremia, conventionally defined as a serum-sodium concentration equal or less than 135 mmol/l (American Heart Association in Heart disease and stroke statistics--2007 update. American Heart Association, Dallas, 2007; Stewart et al. in Eur J Heart Fail 4:361-371, 2002), is a common phenomenon in patients with heart failure, with an incidence of 20-25% (Krumholz et al. in Arch Intern Med 157:e99-e104, 1997; Rosamond et al. in Circulation 117(4):e25-e146, 2008; Adrogue and Madias in N Engl J Med 342:1581-1589, 2000) and seems to be of prognostic importance in patients with heart failure (Luca et al. in Am J Cardiol 96:19L-23L, 2005; Gheorghiade et al. in Eur Heart J 28:980-988, 2007; Gheorghiade et al. in Arch Intern Med 167:1998-2005, 2007). So far treatment strategies have been limited and burdened by side effects. The development of hyponatremia in the setting of heart failure is related to the arginine vasopressin (AVP) dysregulation. Thus, AVP receptor antagonists are a promising approach to treatment. However, several questions remain: whether there is a cause-and-effect mechanism, if the correction of hyponatremia improves outcomes, and defining the specific cut-off level of serum-sodium that should be used to define hyponatremia. In this review, we aim to summarize the literature on hyponatremia in patients with heart failure within several aspects: incidence in clinical trials and registries, prognostic value, underlying mechanisms, therapeutic options, and possible future perspectives.

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Section: Treatment and Avp Antagonismmentioning

confidence: 98%

Significance of hyponatremia in heart failure

Bettari¹,

Fiuzat

Felker

et al. 2010

Heart Fail Rev

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“…The use of an AVP receptor antagonist to treat hyponatremia has other advantages over existing therapies. In patients with CHF, AVP antagonism has the potential to produce effective and sustained reductions in congestion without worsening renal function, potassium depletion, or hypotension that may be associated with diuretics [67]. In low-output CHF, V 2 receptor antagonists can correct the associated conditions of hyponatremia, hypo-osmolality, and water retention [54].…”

Section: Avp Receptor Antagonismmentioning

confidence: 99%

“…A V 1A /V 2 receptor antagonist provides V 2 -mediated renal aquaresis and may suppress the negative hemodynamic and cardiac effects caused by activation of the V 1A receptor [34, 67]. Conivaptan (YM-087) is currently the only agent in this class [77] and has recently been approved by FDA.…”

Section: V1a/v2 Receptor Antagonistmentioning

confidence: 99%

Hyponatremia, Arginine Vasopressin Dysregulation, and Vasopressin Receptor Antagonism

et al. 2006

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Hyponatremia is often associated with arginine vasopressin (AVP) dysregulation that is regulated by the hypothalamo-neurohypophyseal tract in response to changes in plasma osmolality, commonly in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Potentially lethal complications of hyponatremia most frequently involve the central nervous system and include anorexia, fatigue, lethargy, delirium, seizures, hypothermia and coma, and require prompt treatment. Chronic hyponatremia also complicates patient care and is associated with increased morbidity and mortality, particularly among patients with congestive heart failure. Conventional treatments for hyponatremia (e.g. fluid restriction, diuretic treatment, and sodium replacement) may not be effective in all patients and can lead to significant adverse events. Preclinical and clinical trial results have shown that AVP receptor antagonism is a promising approach to the treatment of hyponatremia that directly addresses the effects of increased AVP and consequent decreased aquaresis, the electrolyte-sparing excretion of free water. Agents that antagonize V₂ receptors promote aquaresis and can lead to increased serum sodium. Dual-receptor antagonism, in which both V₂ and V_1A receptors are blocked, may provide additional benefits in patients with hyponatremia.

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“…32 The clinical significance of V 1A receptor antagonism remains to be elucidated, but this approach might suppress the negative hemodynamic and cardiac effects caused by V 1A -mediated vasoconstriction. 40,41 In addition, studies in animal models of subarachnoid hemorrhage and embolic stroke suggest that V 1A receptor antagonism protects against cerebral vasospasm and neurological deficits associated with ischemic brain injury.…”

Section: Avp Receptor Antagonists: a New Approach To The Treatment Ofmentioning

confidence: 98%

Neurological impact of vasopressin dysregulation and hyponatremia

Bhardwaj

2006

Annals of Neurology

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Hyponatremia is frequently associated with neurological disease, neurosurgical procedures, and use of psychoactive drugs. Arginine vasopressin (AVP), or antidiuretic hormone, is the principal physiological regulator of water and electrolyte balance, and disruption of the normal AVP response to osmotic stimuli is a common cause of dilutional hyponatremia in neurological disorders. The hyponatremia-induced shift in water from the extracellular to the intracellular compartment can lead to cerebral edema and serious neurological complications, especially if the decrease in serum sodium concentration ([Na+]) is large or rapid. Overly rapid correction of the serum [Na+] may lead to osmotic demyelination and irreversible brain injury. Fluid restriction is considered first-line treatment and pharmacological agents currently used in the treatment of hyponatremia are limited by inconsistent response and adverse side effects. AVP receptor antagonists represent a new approach to the treatment of hyponatremia by blocking tubular reabsorption of water by binding to V2 receptors in the renal collecting ducts, resulting in aquaresis. Initial clinical experience with AVP receptor antagonists for hyponatremia has shown that these agents augment free water clearance, decrease urine osmolality, and correct serum [Na+] and serum osmolality. Controlled clinical trials now underway will help elucidate the role of AVP receptor antagonism in the treatment of hyponatremia.

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Vasopressin receptor antagonism — a therapeutic option in heart failure and hypertension

Cited by 40 publications

References 49 publications

Significance of hyponatremia in heart failure

Significance of hyponatremia in heart failure

Hyponatremia, Arginine Vasopressin Dysregulation, and Vasopressin Receptor Antagonism

Neurological impact of vasopressin dysregulation and hyponatremia

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