We studied the contribution of vasopressin to the maintenance of high blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertension in the rat using the non-peptide orally effective vasopressin V1 receptor antagonist OPC-21268. Binding kinetic studies demonstrated that oral OPC-21268 (30 mg/kg) acted as a competitive antagonist at the vasopressin V1 receptor in DOCA-salt and salt control rats. Basal mean intra-arterial blood pressure was 140±4 mm Hg (n=12) in DOCA-salt rats compared with 111±2 mm Hg in salt control rats (n=18). Acute oral OPC-21268 (30 mg/kg) significantly (P<.01) reduced mean intra-arterial pressure in DOCA-salt hypertension, with an average maximal decrease of 24±3 mm Hg occurring at 2.5±0.7 hours after dosing. Systolic blood pressure (tail-cuff) in DOCA-salt rats was 178±2 mm Hg. Chronic oral OPC-21268 (30 mg/kg) twice daily for 7 days significantly (P<.01) reduced systolic blood pressure in DOCA-salt hypertension, with an average maximal decrease of 27±5 mm Hg. The antihypertensive effect was reversed 5 days after treatment with OPC-21268 was stopped. In water control rats basal systolic pressure (120±1 mm Hg, n=20) was unchanged by chronic oral OPC-21268 (30 mg/kg twice daily for 7 days), and this was confirmed by direct measurement of mean intra-arterial pressure. After chronic oral OPC- 21268 (30 mg/kg twice daily for 7 days) hepatic V1 receptor binding was significantly reduced for up to 10 hours (P<.05). The results of this study suggest that vasopressin does not play a major role in the regulation of normal blood pressure in the rat but support a role for vasopressin in the maintenance of mineralocorticoid hypertension in the rat. OPC-21268 may be of use in the treatment of hypertensive conditions associated with elevated vasopressin concentrations.
|Number of pages||7|
|Issue number||6 pt.I|
|Publication status||Published - Jun 1994|
- blood pressure
- hypertension, experimental