ENDOTHELIUM-DEPENDENT RELAXATION OF HUMAN SAPHENOUS VEINS IN RESPONSETO VASOPRESSIN AND DESMOPRESSIN

Purpose: The goal of this study was to determine the effects of vasopr essin and the selective V-2-receptor agonist desmopressin on human sap henous 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 t he 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 th e absence of either the V-1-receptor antagonist d(CH2)(5)Tyr(Me)AVP (1 0(-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-ar ginine methyl ester hydrochloride (L-NAME, 10(-4) mol/L). Results: In vein rings under resting tension, vasopressin produced concentration-d ependent, 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) displ aced the control curve to vasopressin 9.86-fold to the right in a para llel 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 indomethaci n (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 endotheli um-dependent relations in precontracted vein rings that were re inhibi ted 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 effec ts on human saphenous vein by V-1-receptor stimulation. Vasopressin ca uses dilatation of human saphenous vein only if V-1-receptor blockade is present. This relaxation appears to be mediated by the release of r elaxant prostaglandins, probably derived from endothelial cells, and i s independent of V-2-receptor stimulation or release of nitric oxide. Desmopressin elicits relaxation that is largely dependent on V-2-recep tor stimulation, which may bring about the release of dilating prostag landins from the endothelial cells.