Molecular Human Reproduction, Vol 4, 71-76, Copyright © 1998 by Oxford University Press
A Jovanovic, S Jovanovic, I Tulic and L Grbovic
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 (pEC50 = 8.06+/-0.14, n = 28). After the
removal of the endothelium this relaxation was abolished (n = 6).
Indomethacin (10 microM), a cyclooxygenase inhibitor, and
diethylcarbamazine (100 microM), a lipoxygenase blocker, had no effects on
VIP-induced relaxation. In contrast, methylene blue (10 microM), a blocker
of guanylate cyclase, NG-monomethyl-L-arginine (10 microM), 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 KA/EC50 was 0.89+/-0.11,
where pKa = log10KA, and KA is the dissociation constant of VIP-receptor
complex. Therefore, on the basis of the results presented, we can conclude
that VIP 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 VIP in human uterine artery can
be entirely explained by the release of NO from endothelial cells.
JOURNAL ARTICLE
Predominant role for nitric oxide in the relaxation induced by vasoactive intestinal polypeptide in human uterine artery
Department of Clinical Pharmacology, Pharmacology and Toxicology, Medical School, Belgrade, Yugoslavia.
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