Vascular responses to vasopressin antagonists in man and rat.
1. The effects of the non-peptide arginine vasopressin V1 receptor antagonist (OPC-21268) and the non-peptide V2 receptor antagonist (OPC-31260) on vasopressin-induced contraction of human internal mammary arteries and rat mesenteric resistance arteries were investigated. 2. In human internal mammary arteries, the non-peptide V1 receptor antagonist, OPC-21268, failed to antagonize vasopressin-induced contraction at low concentrations and potentiated the contraction at higher concentrations (300 nmol/l, P < 0.05). A peptide selective V1 receptor antagonist ([d(CH2)5, sarcosine7]arginine vasopressin) potently inhibited the vasopressin-induced contraction, indicating the presence of functionally constrictor V1 receptors in human internal mammary arteries. Both peptide (desGly-NH29[d(CH2)5, D-Ile2, Ile4]arginine vasopressin) and non-peptide 'selective' V2 receptor antagonists (OPC-31260, 3 mumol/l) significantly antagonized vasopressin-induced contraction (P < 0.01), indicating partial V1 receptor antagonist activity. 3. The vasopressin-induced contraction in human internal mammary arteries was reversed by high concentrations of the non-peptide V2 receptor antagonist, OPC-31260, but not by the non-peptide V1 receptor antagonist, OPC-21268. 4. The effects of OPC-21268 and OPC-31260 were specific to vascular vasopressin receptors as neither compound influenced endothelin- or noradrenaline-induced contraction in human internal mammary arteries. 5. In rat mesenteric resistance arteries, both OPC-21268 (10 nmol/l) and OPC-31260 (1 mumol/l) antagonized vasopressin-induced contraction (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
L M
LM
Burrell
P A
PA
Phillips
K A
KA
Rolls
B F
BF
Buxton
C I
CI
Johnston
J J
JJ
Liu
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology*; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008323:Mammary Arteries / Q000187:drug effects / Q000502:physiology; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014661:Vasoconstriction / Q000187:drug effects*
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D010880:Piperidines; D015363:Quinolones; D001127:Arginine Vasopressin; C068644:OPC 21268; C076251:mozavaptan