Endothelium-dependent relaxation of human saphenous veins in response to vasopressin and desmopressin

Purpose: The goal of this study was to determine the effects of vasopressin and the selective V-2-receptor agonist desmopressin on human saphenous veins, with special emphasis on endothelium-mediated responses. Methods: Human saphenous vein segments were obtained from 35 patients undergoing coronary bypass surgery. Paired segments, one normal and the other deendothelized by gentle rubbing, were mounted for isometric recording of tension in organ baths. Concentration-response curves to vasopressin and desmopressin were determined in the presence and in the absence of either the V-1-receptor antagonist d(CH2)(5)Tyr(Me)AVP (10(-6) mol/L), the V-1-V-2-receptor antagonist desGly-d(CH2)(5)D-Tyr(Et)ValAVP (10(-6) mol/L), indomethacin (10(-6) mol/L), or N-G-nitro-L-arginine methyl ester hydrochloride (L-NAME, 10(-4) mol/L). Results: In vein rings under resting tension, vasopressin produced concentration-dependent, endothelium-independent contractions with a concentration of vasopressin producing half-maximal contractions (EC50) of 3.44 x 10(-8) mol/L. The vasopressin V-1-receptor antagonist (10(-6) mol/L) displaced the control curve to vasopressin 9.86-fold to the right in a parallel manner. In precontracted vein rings previously treated with the V-1-antagonist (10(-6) mol/L), vasopressin caused endothelium-dependent relaxations. This relaxation was reduced significantly by indomethacin (10(-6) mol/L) and unaffected by the V-1-V-2-receptor antagonist (10(-6) mol/L) or by L-NAME (10(-4) mol/L). Desmopressin caused endothelium-dependent relations in precontracted vein rings that were re inhibited by the mixed V-1-V-2-receptor antagonist and by indomethacin, but not by the V-1-antagonist or by pretreatment with L-NAME. Conclusions: These observations indicate that vasopressin exerts contractile effects on human saphenous vein by V-1-receptor stimulation. Vasopressin causes dilatation of human saphenous vein only if V-1-receptor blockade is present. This relaxation appears to be mediated by the release of relaxant prostaglandins, probably derived from endothelial cells, and is independent of V-2-receptor stimulation or release of nitric oxide. Desmopressin elicits relaxation that is largely dependent on V-2-receptor stimulation, which may bring about the release of dilating prostaglandins from the endothelial cells.