DESMOPRESSIN IS A POTENT VASORELAXANT OF AORTA AND PULMONARY-ARTERY ISOLATED FROM RABBIT AND RAT

Hypotension related to the intraoperative use of desmopressin acetate to improve platelet function following cardiopulmonary bypass has recently been reported. To investigate the direct vascular actions of this drug as a potential mechanism of its induced hypotension, cumulative, dose-dependent (3.7 x 10-10 to 1.2 x 10-7 M) effects of desmopressin were studied in isolated phenylephrine precontracted rings of rat and rabbit thoracic aorta and rabbit pulmonary artery. Desmopressin was a potent vasodilator of all vessel types studied with significant (P < 0.05) vasodilation beginning at 7.5 x 10-9 M. Vascular relaxation of all vessels was greater when the vascular endothelium was intact (P < 0.05). Indomethacin potentiated (P < 0.05) vascular relaxation in rat and rabbit aortic rings and partially inhibited (P < 0.05) relaxation in rabbit pulmonary artery rings. Selective antagonists of vasopressin V1 (d(CH2)5-Tyr(Me)AVP, 1 x 10-6 M) and V2 (d(CH2)5[D-Ile2,Ile4,Ala-NH29]AVP, 1 x 10-6 M) receptors and of histamine H1 (diphenydramine, 1 x 10-5 M) and H2 (cimetidine 1 x 10-5 M) receptors had no effect on desmopressin-induced relaxation of rat aortic rings. Chlorobutanol, the diluent in which desmopressin is supplied, was devoid of vascular effects. To study the effects of desmopressin on vascular cyclic GMP and cyclic AMP concentrations, a cultured bovine aortic smooth muscle - rat vascular smooth muscle coculture model was employed. Desmopressin (1 x 10-7 and 1 x 10-8 M) did not significantly alter control values of either cyclic nucleotide. The authors conclude that desmopressin is a potent vasodilator, primarily via a direct action on vascular smooth muscle that is modulated by the endothelium and by dilating and constricting prostaglandins and that this vasodilation could account for the hypotension observed with its clinical use.