Therapeutic Potential of Vasopressin-Receptor Antagonists in Heart Failure

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  • Izumi Yasukatsu
    Department of Pharmacology, Osaka City University Medical School, Japan
  • Miura Katsuyuki
    Applied Pharmacology and Therapeutics, Osaka City University Medical School, Japan
  • Iwao Hiroshi
    Department of Pharmacology, Osaka City University Medical School, Japan

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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: V1a (mainly vascular), V1b (pituitary), and V2 (renal). Vaptans are orally and intravenously active nonpeptide vasopressin-receptor antagonists. Recently, subtype-selective nonpeptide vasopressin-receptor agonists have been developed. A selective V1a-receptor antagonist, relcovaptan, has shown initial positive results in the treatment of Raynaud’s disease, dysmenorrhea, and tocolysis. A selective V1b-receptor antagonist, nelivaptan, has beneficial effects in the treatment of psychiatric disorders. Selective V2-receptor antagonists including mozavaptan, lixivaptan, satavaptan, and tolvaptan induce highly hypotonic diuresis without substantially affecting the excretion of electrolytes. A nonselective V1a/V2-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 V2-receptor antagonists, may have therapeutic potential for heart failure. This review presents current information about AVP and its antagonists.

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