Effect of nonpeptide vasopressin receptor antagonists on developing, and established DOCA-salt hypertension in rats.
Efficacy of orally available, selective vasopressin V1 and V2 receptor antagonists on the developing and established stage of DOCA-salt hypertension was investigated. Twenty-nine Wistar rats were heminephrectomized, and administered DOCA (50 mg/kg; intraperitoneally twice a week) and salt (5% NaCl diet) from week 0 to the end of study. Group 1 rats were served as control. Group 2 and 5 rats were given a V1 antagonist, and groups 3 and 6 rats were given a V2 antagonist, while groups 4 and 7 rats received both V1 and V2 antagonists. Each drug was started to groups 2, 3 and 4 at week 0, and to groups 5, 6 and 7 at week 4. Significant amelioration of the increase in blood pressure was observed in groups 3 and 4 at week 10, and a reduction in blood pressure occurred in groups 6 and 7 at week 10. Otherwise, a V1 antagonist alone slightly attenuated blood pressure rise in the group 2 without significance, and failed to lower blood pressure of the group 5 during the study. These results suggest that both V1 and V2 agonisms are involved in an increase in blood pressure at the developing stage of DOCA-salt hypertension, and that V2 agonism, but not V1 plays a major role in the maintenance of high blood pressure at the established stage.
Okada
H
H
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Suzuki
H
H
Kanno
Y
Y
Saruta
T
T
D000284:Administration, Oral; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight; D003900:Desoxycorticosterone; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D010880:Piperidines; D015363:Quinolones; C068644:OPC 21268; C076251:mozavaptan; D003900:Desoxycorticosterone; D012965:Sodium Chloride