Effects of long-term oral treatment with selective vasopressin V2 receptor antagonist (OPC-31260) on adriamycin-induced heart failure in rats.
BACKGROUND
In the treatment of heart failure, the effects of therapeutic agents on life prognosis remains unclear. We investigated the effects of long-term oral administration of a nonpeptide, selective, vasopressin V2 receptor antagonist, OPC-31260, on Sprague-Dawley rats that were treated with adriamycin to induce progressive water retention.


METHODS
Intraperitoneal saline was administered to 14 rats as a control (Group 1). A total cumulative dose of 15 mg/kg of adriamycin was administered intraperitoneally in six equal doses over a period of 2 weeks to another 52 rats. Adriamycin-treated rats were further divided into Group 2, which received saline (p.o.), and Group 3, which received 50 mg/kg (p.o.) of V2 antagonist. Oral administration continued every day for 6 weeks. Group 1 rats also received saline (p.o.) for 6 weeks.


RESULTS
The V2 antagonist decreased urine osmolality and increased diuresis of rats in Group 3. Urinary excretion of electrolytes was not increased by the V2 antagonist in Group 3. Serum osmolality was likewise unchanged by the V2 antagonist in Group 3. Plasma concentrations of vasopressin were significantly higher in Group 3 than in the other groups (Group 1, 4.0+/-1.1 pg/ml; Group 2, 4.2+/-1.5 pg/ml; Group 3, 8.5+/-1.0 pg/ml; p<0.05). During the experimental period, survival rate was higher in Group 3 than in Group 2 (Group 1, 100%; Group 2, 59%; Group 3, 83%).


CONCLUSIONS
Our data show that administration of orally active V2 antagonist did not reduce the survival of adriamycin-treated rats through continuous aquaretic action, despite elevated plasma levels of vasopressin.
First Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, 23-3 Shimoaizuki, Matsuoka-cho, Yoshida-gun, Fukui, 910-1104, Japan.
Masayuki
M
Takeuchi
Jong-Dae
JD
Lee
Hiromasa
H
Shimizu
Takanori
T
Ueda
D000284:Administration, Oral; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000494:pharmacology*; D004317:Doxorubicin / Q000009:adverse effects; D006333:Heart Failure / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis; D014556:Urine / Q000737:chemistry; D014667:Vasopressins / Q000097:blood
D000903:Antibiotics, Antineoplastic; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D014667:Vasopressins; C076251:mozavaptan; D004317:Doxorubicin