Arginine Vasopressin Enhances Sympathetic Constriction Through the V 1 Vasopressin Receptor in Human Saphenous Vein

Abstract

Background —Arginine vasopressin (AVP) not only acts directly on blood vessels through V 1 receptor stimulation but also may modulate adrenergic-mediated responses in animal experiments in vivo and in vitro. The aim of the present study was to investigate whether AVP can contribute to an abnormal adrenergic constrictor response of human saphenous veins. Methods and Results —Saphenous vein rings were obtained from 32 patients undergoing coronary artery bypass surgery. The vein rings were suspended in organ bath chambers for isometric recording of tension. AVP (3×10 −9 mol/L) enhanced the contractions elicited by electrical field stimulation at 1, 2, and 4 Hz (by 80%, 70%, and 60%, respectively) and produced a leftward shift of the concentration-response curve to norepinephrine (half-maximal effective concentration decreased from 6.87×10 −7 to 1.04×10 −7 mol/L; P <.05). The V 1 vasopressin receptor antagonist d(CH 2 ) 5 Tyr(Me)AVP (10 −6 mol/L) prevented the potentiation evoked by AVP. The selective V 1 receptor agonist [Phe, 2 Orn 8 ]-vasotocin (3×10 −9 mol/L) induced potentiation of electrical stimulation–evoked responses, which was also inhibited in the presence of the V 1 receptor antagonist (10 −6 mol/L). In contrast, the V 2 receptor agonist desmopressin (10 −9 to 10 −7 mol/L) did not modify neurogenic responses, and the V 2 receptor antagonist [d(CH 2 ) 5 , D-Ile, 2 Ile, 4 Arg 8 ]-vasopressin (10 −8 to 10 −6 mol/L) did not prevent the potentiation induced by AVP. The dihydropyridine calcium antagonist nifedipine (10 −6 mol/L) did not affect the potentiating effect of AVP. Conclusions —The results suggest that low concentrations of AVP facilitate sympathetic neurotransmission and potentiate constrictor effects of norepinephrine in human saphenous veins. These effects appear to be mediated by V 1 receptor stimulation and are independent of calcium entry through dihydropyridine calcium channels. Thus, AVP may contribute to vascular mechanisms involved in acute ischemic syndromes associated with venous grafts, particularly if the sympathetic nervous system is activated.