title: V2 receptor antagonism with tolvaptan in heart failure.
abstract: The prevalence and incidence of congestive heart failure continues to increase. The two hallmarks of this syndrome, sodium and water retention, are frequently a therapeutic challenge. Most conventional diuretics act primarily as saluretics by inhibiting renal tubular electrolyte reabsorption, which, due to osmotic pressure, promotes excretion of isotonic fluid. The peptide hormone arginine vasopressin vasoconstricts at the V(1A) receptor and promotes water reabsorption via the V(2) receptor in the renal collecting duct by inserting aquaporin-2 water channels into the luminal membrane. Tolvaptan, the first orally available non-peptide V(2) receptor antagonist, acts as a potent aquaretic. In this paper, the authors review the pharmacology of tolvaptan and discuss the results of the initial clinical trials with this potent new drug.
authors.affiliation: Cardiorenal Research Laboratory, Mayo Clinic and Mayo Clinic College of Medicine, Guggenheim 9, 200 First Street SW, Rochester, MN 55905, USA. costello.lisa@mayo.edu
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Costello-Boerrigter
authors.forename: Guido
authors.initials: G
authors.lastname: Boerrigter
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000378:metabolism; D001552:Benzazepines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004232:Diuretics / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D000077602:Tolvaptan
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D004232:Diuretics; D001127:Arginine Vasopressin; D000077602:Tolvaptan