Vasopressin Receptor Blocker Acts Against Polycystic Kidney Disease In Mice

NEW YORK (Reuters Health) - OPC31260, a vasopressin V2 receptor (VPV2R) antagonist, is effective in treating a murine model of autosomal dominant polycystic kidney disease (ADPKD) researchers report in the February 29th online edition of Nature Medicine.

Dr. Vincente E. Torres of the Mayo Clinic College of Medicine, Rochester, Minnesota and colleagues note that the agent has already been shown to be useful in rat and mouse models of PKD that are "probably related."

To investigate further, the researchers added OPC31260 to the diet of an ADPKD-susceptible variety of mice at between 3 and 16 weeks of age. Such animals reliably develop renal cysts within 3 months and also show higher levels of cAMP, aquaporin-2 and VP2VR than do wild type mice.

The agent markedly reduced renal accumulation of cAMP and corrected the overexpression of aquaporin-2 and VP2VR. In addition it "markedly reduced" disease development.

Furthermore, possibly because of its renoselectivity, say the investigators, OPC31260 was well tolerated and did not cause any electrolyte abnormalities. They also note that several VPV2R antagonists are undergoing trials to study their action against conditions such as congestive hear failure.

"Given the present lack of effective therapies and the apparent safety of VPV2R antagonists," the researchers conclude, "clinical trials of these compounds in ADPKD seem appropriate."

Source: Nat Med 2004. [ Google search on this article ]

MeSH Headings: Kidney, Cystic : Kidney, Polycystic : Kidney, Polycystic, Autosomal Dominant

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