Endothelium-dependent relaxation of human saphenous veins in response to vasopressin and desmopressin.
OBJECTIVE
The goal of this study was to determine the effects of vasopressin and the selective V2-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 V1-receptor antagonist d(CH2)5Tyr (Me)AVP (10(-6) mol/L), the V1-V2-receptor antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (10(-6) mol/L), indomethacin (10(-6) mol/L), or NG-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 V1-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 V1-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 V1-V2-receptor antagonist (10(-6) mol/L) or by L-NAME (10(-4) mol/L). Desmopressin caused endothelium-dependent relaxations in precontracted vein rings that were inhibited by the mixed V1-V2-receptor antagonist and by indomethacin, but not by the V1-antagonist or by pretreatment with L-NAME.


CONCLUSIONS
These observations indicate that vasopressin exerts contractile effects on human saphenous vein by V1-receptor stimulation. Vasopressin causes dilatation of human saphenous vein only if V1-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 V2-receptor stimulation or release of nitric oxide. Desmopressin elicits relaxation that is largely dependent on V2-receptor stimulation, which may bring about the release of dilating prostaglandins from the endothelial cells.
Aldasoro
M
M
Department of Physiology, University of Valencia, Spain.
Medina
P
P
Vila
J M
JM
Otero
E
E
Martinez-León
J B
JB
Lluch
S
S
D000328:Adult; D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007537:Isometric Contraction; D008297:Male; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011453:Prostaglandins / Q000494:pharmacology; D017483:Receptors, Vasopressin / Q000819:agonists; D012501:Saphenous Vein / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology; D014667:Vasopressins / Q000008:administration & dosage / Q000494:pharmacology*; D014668:Vasotocin / Q000031:analogs & derivatives / Q000494:pharmacology
D065092:Antidiuretic Hormone Receptor Antagonists; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D006727:Hormone Antagonists; D011453:Prostaglandins; D017483:Receptors, Vasopressin; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C089517:vasopressin, 1-(2-mercapto-2,2-(cyclopentamethylene)propionic acid)-2-(O-methyl)Tyr-8-Arg-; D014667:Vasopressins; D001127:Arginine Vasopressin; C076093:vasotocin, (beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)-O-methyl-Tyr(2)-Thr(4)-Orn(8)-Tyr(9)-NH2; D019001:Nitric Oxide Synthase; D003894:Deamino Arginine Vasopressin; D019331:NG-Nitroarginine Methyl Ester; D014668:Vasotocin; D007213:Indomethacin