title: Anti-edematous effects of tolvaptan in experimental rodent models.
abstract: OBJECTIVE
  The aim of this study was to evaluate the therapeutic efficacy of tolvaptan, a vasopressin V(2) receptor antagonist, on edema in two rat models: 1) histamine-induced vascular hyperpermeability of the dorsal skin and 2) carrageenan-induced paw edema.
  
  
  METHODS
  In the skin vascular hyperpermeability model, 3 h after oral administration of tolvaptan or the natriuretic agent furosemide, rats were intravenously injected with Evans Blue (EB), followed by intradermal injection of 10 μg of histamine into the dorsal skin. One hour later, blood was collected to measure serum parameters. EB leakage area into the dorsal skin was also measured. Urine was collected for 4 h to determine urine parameters. In the paw edema model, edema was induced by injecting 1% w/v carrageenan into the right hind paw. Paw volume was measured hourly for 5 h. Tolvaptan or furosemide was orally administered 1 h before carrageenan injection.
  
  
  RESULTS
  A single oral dose of tolvaptan (1-10 mg/kg) elicited marked and dose-dependent aquaresis, and improvements in edema. Similar effects were observed with furosemide (30 mg/kg). Tolvaptan tended to elevate the serum sodium level while furosemide caused a significant decrease.
  
  
  CONCLUSIONS
  Tolvaptan had anti-edematous effects in two different rat models. By increasing free water excretion, tolvaptan may be more advantageous for certain patients than loop diuretics because it does not cause electrolyte loss, and may prevent electrolyte abnormities, such as hyponatremia. These results suggest that tolvaptan has potential clinical benefits for the treatment of edema.
authors: First Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima, 771-0192, Japan.
authors: Toshiki
authors: T
authors: Miyazaki
authors: Yuki
authors: Y
authors: Sakamoto
authors: Tatsuya
authors: T
authors: Yamashita
authors: Koji
authors: K
authors: Ohmoto
authors: Hiroyuki
authors: H
authors: Fujiki
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000627:therapeutic use*; D002351:Carrageenan; D004195:Disease Models, Animal; D004232:Diuretics / Q000627:therapeutic use*; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D005534:Foot Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000652:urine; D006632:Histamine; D008297:Male; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017445:Skin Diseases, Vascular / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000652:urine; D012964:Sodium / Q000097:blood / Q000652:urine; D000077602:Tolvaptan
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D004232:Diuretics; D000077602:Tolvaptan; D006632:Histamine; D002351:Carrageenan; D012964:Sodium