PREDOMINANT ROLE FOR NITRIC-OXIDE IN THE RELAXATION INDUCED BY VASOACTIVE INTESTINAL POLYPEPTIDE IN HUMAN UTERINE ARTERY

It has been previously shown that vasoactive intestinal polypeptide (V IP) induces endothelium-dependent relaxation of the human uterine arte ry. However, the nature of the mediator of the VIP-induced endothelium -dependent relaxation of the human uterine artery has not yet been det ermined. Therefore these experiments were undertaken to examine the ef fects of VIP on human uterine arteries and to establish the role of va rious endothelial factors on the relaxation induced by VIP. The experi ments were performed on isolated human uterine arterial rings. VIP (0. 3-100 nM) induced a concentration-dependent relaxation of human uterin e arteries with intact endothelium (PEC50 = 8.06 +/- 0.14, n = 28). Af ter the removal of the endothelium this relaxation was abolished (n = 6). Indomethacin (10 mu M), a cyclooxygenase inhibitor, and diethylcar bamazine (100 mu M), a lipoxygenase blocker, had no effects on VIP-ind uced relaxation. In contrast, methylene blue (10 mu M), a blocker of g uanylate cyclase, N-G-monomethyl-L-arginine (10 mu M), an inhibitor of nitric oxide (NO) synthase, and 4-aminopyridine (1 mM), a non-selecti ve blocker of K+ channels, antagonized the effect of VIP with suppress ion of maximal VIP-induced relaxation. Non-competitive antagonism with methylene blue revealed that the pKa value for VIP-receptor complex w as 8.10 +/- 0.10 (n = 6) and the receptor reserve expressed as K-A/EC5 0 was 0.89 +/- 0.11, where pKa = log(10)K(A), and K-A is the dissociat ion constant of VIP-receptor complex. Therefore, on the basis of the r esults presented, we can conclude that VIP induces endothelium-depende nt relaxation in human uterine arteries, acting as a partial agonist o n this blood vessel. It appears that endothelium-dependent relaxation induced by VIP in human uterine artery can be entirely explained by th e release of NO from endothelial cells.