POTENT INHIBITORY EFFECT OF SR-49059, AN ORALLY-ACTIVE NONPEPTIDE VASOPRESSIN V1A 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 internal mammary arteries. Both SR (1 mu mol/l) and a peptide selective Via antagonist {[d(CH2)(5) sarcosine(7)]arginine vasopressin} (1 mu mol/l) abolished vasopressin-induced contraction. The nonpeptide V1a receptor antagonist OPC-21268 (1 mu mol/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.