EFFECTS OF VASOPRESSIN V-1 AND V-2 RECEPTOR ANTAGONISTS ON PROGRESSIVE RENAL-FAILURE IN RATS

1. The relationship between vasopressin and the progression of renal failure has been proposed, but not intensively investigated because of a lack of orally available, selective vasopressin antagonists. 2. The effects of novel, orally available vasopressin V-1 and V-2 receptor antagonists on several indices of the progression of chronic renal failure, i.e. blood pressure, urinary protein excretion, sodium balance and renal histopathology, were investigated by using Wistar rats with adriamycin-induced nephropathy accelerated by deoxycorticosterone acetate-salt hypertension. Groups 2 and 3 were treated with V-1 and V-2 antagonists, respectively, while the untreated group 1 served as the control. To block the effects of vasopressin efficaciously, V-1 and V-2 antagonists were simultaneously administered (group 4). 3. At week 6, 2 weeks after the beginning of administration of deoxycorticosterone acetate-salt and vasopressin antagonists after the second injection of adriamycin, V-1 and V-2 antagonists given either alone or in combination significantly reduced the systolic blood pressure as compared with the control, and urine volume was increased in groups 3 and 4. The proteinuria was also decreased at week 10 in groups 2, 3 and 4. Differences in sodium excretion between all groups were not significant. Histopathological alterations in the kidneys of group 4 were significantly ameliorated. 4. These results suggest that a combination of V-1 and V-2 antagonists can have therapeutic effects in certain types of chronic renal failure.