Predominant role for nitric oxide in the relaxation induced by vasoactive intestinal polypeptide in human uterine artery

Abstract

It has been previously shown that vasoactive intestinal polypeptide (VIP) induces endothelium-dependent relaxation of the human uterine artery. However, the nature of the mediator of the VIP-induced endothelium-dependent relaxation of the human uterine artery has not yet been determined. Therefore these experiments were undertaken to examine the effects of VIP on human uterine arteries and to establish the role of various endothelial factors on the relaxation induced by VIP. The experiments were performed on isolated human uterine arterial rings. VIP (0.3-100 nM) induced a concentration- dependent relaxation of human uterine arteries with intact endothelium (pEC 50 = 8.06 ± 0.14, n = 28). After the removal of the endothelium this relaxation was abolished (n = 6). Indomethacin (10 μM), a cyclooxygenase inhibitor, and diethylcarbamazine (100 μM), a lipoxygenase blocker, had no effects on VIP-induced relaxation. In contrast, methylene blue (10 μM), a blocker of guanylate cyclase, N(G)-monomethyl-L-arginine (10 μM), an inhibitor of nitric oxide (NO) synthase, and 4-aminopyridine (1 mM), a non- selective blocker of K + channels, antagonized the effect of VIP with suppression of maximal VIP-induced relaxation. Non-competitive antagonism with methylene blue revealed that the pKa value for VIP-receptor complex was 8.10 ± 0.10 (n = 6) and the receptor reserve expressed as K(A)/EC 50 was 0.89 ± 0.11, where pKa = log 10 K(A), and K(A) is the dissociation constant of VlP-receptor complex. Therefore, on the basis of the results presented, we can conclude that VlP induces endothelium-dependent relaxation in human uterine arteries, acting as a partial agonist on this blood vessel. It appears that endothelium-dependent relaxation induced by VlP in human uterine artery can be entirely explained by the release of NO from endothelial cells.