The aim of this work was to investigate histopathologically the relationship between the syndrome of inappropriate secretion of
antidiuretic hormone (
SIADH) and kidney abnormalities and the therapeutic efficacy of
VP-343 ((N-[4-[[(2S,3aR)-2-hydroxy-2,3,3a,4-tetrahydropyrrolo[1,2-alqunoxalin-5(1H)-yl]phenyl]-4'-methyl[1,1'-
biphenyl]-2-carboxamide], a selective
vasopressin V2 receptor antagonist, in an experimental
SIADH rat model. In the model, which was prepared by continuously administering 1-desamino-8-D-
arginine vasopressin (
DDAVP), histopathologic abnormalities, such as dilatation of tubules, basophilic changes in tubules, inflammatory cell infiltration, and mineralization were found in the kidney, accompanied by significant increases in the relative weight of the kidney, lung, liver, adrenal gland, and heart.
VP-343 was shown to be effective in protecting the kidney from the histopathologic abnormalities and to normalize the relative weight of the kidney and several common pathophysiologic features, such as
hyponatremia, hyposmolarity of plasma, hyperosmolarity of
urea, and oligurea, as described previously. These results demonstrate the occurrence of histopathologic abnormalities in the kidney and the efficacy of
VP-343 in improving abnormalities in the
DDAVP-induced
SIADH rat model.