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Title: Blood pressure-lowering effect of an orally active vasopressin V1 receptor antagonist in mineralocorticoid hypertension in the rat.
Austin Authors: Burrell, Louise M ;Phillips, P A;Stephenson, J M;Risvanis, John;Rolls, K A;Johnston, Colin I
Affiliation: University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia
Issue Date: 1-Jun-1994
Publication information: Hypertension; 23(6 Pt 1): 737-43
Abstract: We studied the contribution of vasopressin to the maintenance of high blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertension in the rat using the nonpeptide 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).(ABSTRACT TRUNCATED AT 250 WORDS)
Gov't Doc #: 8206571
Journal: Hypertension
Type: Journal Article
Subjects: Administration, Oral
Antidiuretic Hormone Receptor Antagonists
Arginine Vasopressin.metabolism
Binding Sites
Blood Pressure.drug effects
Hypertension.chemically induced.physiopathology
Mesenteric Arteries.drug effects
Rats, Sprague-Dawley
Receptors, Vasopressin.classification
Sodium Chloride
Vascular Resistance.drug effects
Appears in Collections:Journal articles

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