Potent inhibitory effect of SR 49059, an orally active non-peptide vasopressin VIa receptor antagonist, on human arterial coronary bypass graft.
1. The effect of vasopressin receptor antagonists varies between analogues (peptide, non-peptide) and across species. In this study the effect of the novel non-peptide vasopressin V1a receptor antagonist SR 49059 on human internal mammary arteries was investigated. 2. SR 49059 produced a potent, concentration-dependent, inhibitory effect on vasopressin-induced contraction of human coronary bypass graft internal mammary arteries. Both SR 49059 (1 mumol/l) and a peptide selective V1a antagonist ([d(CH2)5sarcosine7]arginine vasopressin) (1 mumol/l) abolished vasopressin-induced contraction. The non-peptide V1a receptor antagonist OPC-21268 (1 mumol/l) had no effect on vasopressin-induced contraction. 3. The effect of SR 49059 was specific to vascular vasopressin receptors as noradrenaline-induced contraction was not influenced by SR 49059. 4. The results of this study in vitro indicate that the non-peptide SR 49059 is a potent, specific vasopressin V1a receptor antagonist in the human internal mammary artery and suggest that it may be a useful tool for studying the pathophysiological role of vasopressin in man.
Department of Cardiac Surgery, University of Melbourne, Austin, Australia.
J J
JJ
Liu
J R
JR
Chen
B B
BB
Buxton
C I
CI
Johnston
L M
LM
Burrell
D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors*; D001158:Arteries / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008323:Mammary Arteries; D009119:Muscle Contraction / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology*
D065092:Antidiuretic Hormone Receptor Antagonists; D006727:Hormone Antagonists; D007211:Indoles; D011759:Pyrrolidines; D001127:Arginine Vasopressin; C082134:relcovaptan