Evidence for the involvement of vasopressin in the pathophysiology of adriamycin-induced nephropathy in rats.
The effect of orally available, nonpeptide vasopressin V1 and V2 receptor antagonists on chronic progressive glomerular disease was investigated in Wistar rats with Adriamycin-induced nephropathy. At weeks 0 and 3, Adriamycin was injected twice, and at week 3 drugs started to be given as follows: groups 2 and 3 were treated with V1 and V2 antagonists, respectively, while the untreated group 1 served as control. To block the effects of vasopressin totally, both V1 and V2 antagonists were simultaneously administered (group 4). At weeks 8 and 10, V1 and V2 antagonists given either alone or combined significantly reduced the urinary protein excretion to the same levels. Urinary volume increased in groups 3 and 4 from week 4. Systolic blood pressure did not significantly increase in all groups during the study. Histological alterations in the kidney of groups 2, 3 and 4 were significantly attenuated compared to the control. These results suggest that both vasopressin V1 and V2 agonism plays a role in the pathophysiology of Adriamycin-induced nephropathy despite plasma levels of vasopressin within the normal range. These findings also lead to the notion that in some types of nephrotic patients these orally available V1 and/or V2 receptor antagonists may be effective for reduction of proteinuria and for retardation of progression of renal failure.
Okada
H
H
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Suzuki
H
H
Kanno
Y
Y
Saruta
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004317:Doxorubicin / Q000633:toxicity*; D004435:Eating / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000378:metabolism; D014667:Vasopressins / Q000502:physiology*
D000903:Antibiotics, Antineoplastic; D017483:Receptors, Vasopressin; D014667:Vasopressins; D004317:Doxorubicin