RELAXATION OF HUMAN ISOLATED MESENTERIC-ARTERIES BY VASOPRESSIN AND DESMOPRESSIN

1 The effects of vasopressin and deamino-8-D-arginine vasopressin (DDAVP, desmopressin) were studied in artery rings (0.8-1 mm in external diameter) obtained from portions of human omentum during the course of abdominal operations (27 patients). 2 In arterial rings under resting tension, vasopressin produced concentration-dependent, endothelium-independent contractions with an EC(50) of 0.59 +/- 0.12 nM. The V-1 antagonist d(CH2)(5)Tyr(Me)AVP (1 mu M) and the mixed V-1-V-2 antagonist desGly-d(CH2)(5)D-Tyr(Et)ValAVP (0.01 mu M) displaced the control curve to vasopressin to the right in a parallel manner without differences in the maximal responses. In the presence of indomethacin (1 mu M) the contractile response to vasopressin was significantly increased (P<0.01), 3 In precontracted arterial rings, previously treated with the V-1 antagonist, d(CH2)(5)Tyr(Me)AVP (1 mu M), vasopressin produced endothelium-dependent relaxation. This relaxation was reduced significantly (P<0.05) by indomethacin (1 mu M) and unaffected by the V-1-V-2 receptor antagonist desGly- d(CH2)(5)D-Tyr(Et)ValAVP (1 mu M) Or by N-G-nitro-L-arginine methyl ester (L-NAME, 0.1 mM). 4 The selective V-2 receptor agonist, DDAVP, caused endothelium-independent, concentration-dependent relaxations in precontracted arterial rings that were inhibited by the mixed V-1-V-2 receptor antagonist, but not by the V-1 receptor antagonist or by pretreatment with indomethacin or L-NAME. 5 Results from this study suggest that vasopressin is primarily a constrictor of human mesenteric arteries by V-1 receptor stimulation; vasopressin causes dilatation only during V-1 receptor blockade. The relaxation appears to be mediated by the release of vasodilator prostaglandins from the endothelial cell layer and is independent of V-2 receptor stimulation or release of nitric oxide. In contrast, the relaxation induced by DDAVP is largely dependent on stimulation of V-2 receptors.