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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arginine vasopressin plays an important role in volume homeostasis. Patients with heart failure have chronically elevated plasma vasopressin concentrations which may contribute to their clinical syndrome of fluid retention. Recently, a number of agents have been developed to antagonize the effects of vasopressin by targeting its V1a and V2 receptors, which are involved in vascular tone and free water regulation, respectively. Two vasopressin antagonists, in particular, tolvaptan and conivaptan, have shown promise in animal studies and small-scale human trials. The following is a review of current experimental and clinical studies using vasopressin antagonists and their potential role in the treatment of heart failure.
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PMID:Vasopressin antagonism: a future treatment option in heart failure. 1569 26

Despite favorable improvements in mortality, heart failure (HF) remains a problematic illness due to the ever-present burden of hospitalization. Clearly, novel treatment strategies are needed. This review focuses on two newer pharmacologic targets: arginine vasopressin and aldosterone. Arginine vasopressin receptor antagonists will most likely serve as an adjunct to or replacement of standard diuretic therapy in selected patients. The safety and efficacy of chronic therapy with oral arginine vasopressin receptor antagonists in large groups of congestive HF patients is currently under investigation. Aldosterone antagonism is emerging as a treatment of severe congestive HF. Recent large-scale clinical trials using aldosterone antagonists have proven that those with HF or left ventricular dysfunction postmyocardial infarction derive a survival benefit from aldosterone antagonism. Whether aldosterone antagonism should be prescribed in all patients with HF is unclear; however, in carefully selected and managed patients, aldosterone antagonism is helpful.
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PMID:Novel therapies for heart failure: vasopressin and selective aldosterone antagonists. 1572 67

Diuretics are frequently required to treat fluid retention in patients with congestive heart failure (CHF). Unfortunately, they can lead to a decline in renal function, electrolyte depletion, and neurohumoral activation. Arginine vasopressin (AVP) promotes renal water reabsorption via the V2 receptor, and its levels are increased in CHF. This study was designed to assess the effects of a single oral dose of tolvaptan, a selective V2-receptor blocker, in the absence of other medications, on renal function in human CHF and to compare this to the effects of a single oral dose of furosemide. We hypothesized that V2-receptor antagonism would yield a diuresis comparable to furosemide but would not adversely affect renal hemodynamics, plasma electrolyte concentration, or neurohumoral activation in stable human CHF. Renal and neurohumoral effects of tolvaptan and furosemide were assessed in an open-label, randomized, placebo-controlled crossover study in 14 patients with NYHA II-III CHF. Patients received placebo or 30 mg of tolvaptan on day 1 and were crossed over to the other medication on day 3. On day 5, all subjects received 80 mg of furosemide. Tolvaptan and furosemide induced similar diuretic responses. Unlike tolvaptan, furosemide increased urinary sodium and potassium excretion and decreased renal blood flow. Tolvaptan, furosemide, and placebo did not differ with respect to mean arterial pressure, glomerular filtration rate, or serum sodium and potassium. We conclude that tolvaptan is an effective aquaretic with no adverse effects on renal hemodynamics or serum electrolytes in patients with mild to moderate heart failure.
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PMID:Vasopressin-2-receptor antagonism augments water excretion without changes in renal hemodynamics or sodium and potassium excretion in human heart failure. 1618 91

Treatment of chronic heart failure (HF) is based on interference with the renin-angiotensin-aldosterone system and the adrenergic nervous system. Diuretics are used in volume-expanded patients. Insights from clinical trials and registries establish the need to consider correcting both cardiac loading conditions and nonload-related biological factors if HF therapy is to be optimized. Arginine vasopressin (AVP) represents a potentially attractive target for therapy in both acute and chronic HF. Excessive AVP secretion could contribute to both systolic and diastolic wall stress via V1a- and V2-mediated effects on the peripheral vasculature and on water retention. Arginine vasopressin also may directly and adversely affect myocardial function due to the effect of V1a activation on myocardial contractility and cell growth. Last, AVP may contribute to hyponatremia, a powerful predictor of poor outcome in HF. The development of effective nonpeptide antagonists to both the V1a and V2 receptors for AVP now allows for testing the hypotheses that interfering with AVP-mediated signaling could be beneficial in HF. This review summarizes the theoretical rationale for further development of such therapy, reviews the status of current compounds under development, and suggests key issues that need to be addressed as these agents undergo further clinical testing.
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PMID:Vasopressin antagonism in heart failure. 1628 60

Heart failure commonly manifests as a syndrome of salt and water retention. Arginine vasopressin plays an important role in volume homeostasis and may contribute to this syndrome seen in heart failure patients. Recently, a number of agents have been developed that antagonize the effects of vasopressin. Conivaptan, which is a dual antagonist of the V1a and V2 receptor, has shown promise in animal studies and in small scale human trials as a potential therapeutic option for the treatment of acute and chronic heart failure. Further large studies are being conducted, which may confirm the benefits of conivaptan and other vasopressin antagonists in heart failure patients.
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PMID:Conivaptan: a selective vasopressin antagonist for the treatment of heart failure. 1637 24

Arginine vasopressin (AVP) signals predominantly through the V1a receptor, which subserves vasoconstriction in the peripheral circulation, and is linked directly to stimulation of myocardial hypertrophic growth factors, and the V2 receptor, the main function of which is to alter the expression of aquaporin channels in the renal collecting ducts, which leads to water retention. Agents that antagonize or block these receptors could be expected to reduce vascular tone (assuming sufficient V1a signaling is present to be causing an effect), reduce direct mitogenic signaling in the myocardium (again assuming sufficient V1a effect is present), and increase water excretion (assuming sufficient V2 signaling is present). The case for antagonizing both sets of receptors depends on the clinical situation. Pure V1a antagonists might be useful in treatment of hypertension or heart failure, but they are of little use in hyponatremia unless it is caused by heart failure. V2 antagonists would be useful in any euvolemic or hypervolemic condition associated with hyponatremia and may help produce an effective and safe diuresis independent of serum sodium when used in conjunction with loop diuretics in patients with heart failure. Selective blockade of either receptor could lead to increased signaling at the unblocked receptor sites, potentially a problematic result, especially in heart failure where disease progression is affected by increased afterload, preload, and the direct myocardial effects of neurohormonal imbalance. Therefore, a strong rationale exists for the use of combined vasopressin antagonists in patients with heart failure, particularly if the agents are used on a chronic basis.
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PMID:Is there a cardiovascular rationale for the use of combined vasopressin V1a/V2 receptor antagonists? 1684 92

Hyponatremia is a common electrolyte disorder with the potential to cause serious neurological complications. Conventional therapies for hyponatremia have been found to be inconsistently effective. Arginine vasopressin (AVP) is etiologically critical for hyponatremia, and it has been proven that AVP receptor (AVP-R) antagonists normalize serum sodium levels in hyponatremic patients. Additionally, one of these drugs showed potential for reducing mortality in patients with decompensated heart failure and for suppressing the progression of genetic renal disease in animals. The first non-peptide AVP-R antagonist has recently been approved in the United States. It is expected that this approval will accelerate the development of future clinical applications of AVP-R antagonists and open the door to a new era in the treatment of these intractable diseases.
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PMID:Vasopressin receptor antagonists: potential indications and clinical results. 1729 70

Arginine vasopressin (AVP) is a neuropeptide hormone that plays an important role in circulatory and sodium homeostasis, and regulating serum osmolality. Several clinical conditions have been associated with inappropriately elevated levels of AVP including heart failure, cirrhosis of the liver and the syndrome of inappropriate secretion of antidiuretic hormone. Three receptor subtypes that mediate the actions of AVP have been identified (V(1A), V(2) and V(1B)). Activation of V(1A) receptors located in vascular smooth muscle cells and the myocardium results in vasoconstriction and increased afterload and hypertrophy. The V(2) receptors located primarily in the collecting tubules mediate free water absorption. The V(1B) receptors are located in the anterior pituitary and mediate adrenocorticotropin hormone release. The cardiovascular and renal effects of AVP are mediated primarily by V(1A) and V(2) receptors. Antagonism of V(1A) receptors results in vasodilatation and antagonism of V(2) receptors resulting in aquaresis, an electrolyte-sparing water excretion. Several non-peptide AVP antagonists (vasopressin receptor antagonists [VRAs]) also termed 'vaptans' have been developed and are vigorously being studied primarily for treating conditions characterised by hyponatraemia and fluid overload. Conivaptan is a combined V(1A)/V(2)-receptor antagonist that induces diuresis as well as haemodynamic improvement. It has been shown in clinical trials to correct euvolaemic and hypervolaemic hyponatraemia, and has been approved by the US FDA for the treatment of euvolaemic hyponatraemia as an intravenous infusion. Tolvaptan, a selective V(2)-receptor antagonist, has undergone extensive clinical studies in the treatment of hyponatraemia and heart failure. It has been shown to effectively decrease fluid in volume overloaded patients with heart failure and to correct hyponatraemia. A large outcome study (n = 4133 patients) will define its role in the management of heart failure. Lixivaptan and satavaptan (SR-121463) are other selective V(2)-receptor antagonists being evaluated for the treatment of hyponatraemia. In addition, a potential role for the vaptans in attenuating polyuria in nephrogenic diabetes insipidus and cyst development in polycystic kidney disease is being explored. Ongoing clinical trials should further define the scope of the potential therapeutic role of VRAs.
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PMID:Therapeutic potential of vasopressin receptor antagonists. 1742 3

Arginine vasopressin (AVP) plays an important role in volume homeostasis and cardiovascular regulation. This review briefly describes recent clinical studies which evaluated the significance of AVP in cardiovascular diseases. Several AVP receptor antagonists, including tolvaptan and conivaptan, have shown promise in human trials for the treatment of heart failure. As plasma AVP concentrations are elevated in patients with heart failure in accordance with their severity, elevated AVP may contribute to their clinical syndrome of fluid retention and vasoconstriction. In some forms of hypertension, circulating AVP are also elevated; however, the precise role of AVP in the pathophysiology of hypertension is controversial. We performed a case-control study in a random sample of 620 rural residents and found an association between nonobese hypertension and -6951G/A single nucleotide polymorphism in the promoter region of the AVP V1a receptor gene. Our results suggest that AVP might contribute to the subdivision of human hypertension. Antiplatelet agents have been shown effective to prevent cardiovascular events. AVP has been known to stimulate platelet aggregation through V1a receptor. Genetic factors are thought to be involved in the heterogeneity of platelet activation. Some studies have been undertaken to identify genetic markers of platelet sensitivity to AVP.
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PMID:[Recent progress in vasopressin research on cardiovascular diseases]. 1765 88

Diuretics are frequently required to treat fluid retention in patients with chronic heart failure (CHF). Unfortunately, they can lead to a decline in renal function, electrolyte depletion, and neurohormonal activation. Arginine vasopressin (AVP) promotes renal water reabsorption via the V(2) receptor (V(2)R) and its levels are increased in CHF. This study was conducted to characterize the diuretic effect of tolvaptan, a non-peptide AVP V(2)R antagonist, and furosemide, a loop diuretic in a rat model of CHF after experimental autoimmune myocarditis. CHF was elicited in Lewis rats by immunization with porcine cardiac myosin, and 28 days after immunization rats were treated for 28 days with oral tolvaptan, and furosemide. CHF was characterized by left ventricular remodeling and impaired systolic and diastolic function. Tolvaptan produces a diuresis comparable to furosemide. Unlike tolvaptan, furosemide significantly increased urinary sodium and potassium excretion. Tolvaptan markedly elevated electrolyte-free water clearance (E-CH(2)O) or aquaresis to a positive value and increased urinary AVP excretion. In contrast to tolvaptan, furosemide elevated only electrolyte clearance (E-Cosm) but not E-CH(2)O. The differences in diuretic profile reflected the changes in plasma sodium and hormone levels. Tolvaptan dose dependently elevated plasma sodium concentration, but furosemide tended to decrease it. Furosemide significantly elevated plasma renin activity and aldosterone concentration. On the other hand, tolvaptan did not affect these parameters. Our results suggest that, tolvaptan have a potential medical benefit for the treatment of edematous conditions in CHF by removing excess water from the body without activating the RAAS or causing serum electrolyte imbalances.
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PMID:Effects of V2-receptor antagonist tolvaptan and the loop diuretic furosemide in rats with heart failure. 1817 82


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