Y. Okatani et al., Weak vasoconstrictor activity of melatonin in human umbilical artery: relation to nitric oxide-scavenging action, EUR J PHARM, 417(1-2), 2001, pp. 125-129
We evaluated the nitric oxide (NO)-scavenging property of melatonin, demons
trated in a recent in vitro study, on vascular reactivity in the human umbi
lical artery. Helical sections of human umbilical artery were prepared foll
owing elective Cesarean deliveries near term. Changes in maximal tension in
duced by prostaglandin F-2 alpha (5 X 10(-5) M) were measured in artery sec
tions with an intact endothelium. Melatonin at concentrations higher than 1
0(-6) M increased prostaglandin F-2 alpha-induced vascular tension. The vas
ospastic effect of melatonin was much less than that of L-N-G-monomethylarg
inine (L-NMA, 2 X 10(-4) M), an inhibitor of NO synthesis (2.8 +/- 1.4%, 9.
1 +/- 1.7%, 16.5 +/- 2.5%, and 29.6 +/- 5.9% of the L-NMA effect at melaton
in concentrations of 10(-8), 10(-7), 10(-6), and 10(-5) M, respectively). R
emoval of the mdothelium significantly reduced the vasoconstrictive effect
of melatonin. Treatment with.-NMA (2 x 10(-4) M) prior to addition of prost
aglandin F-2 alpha also significantly reduced the vasoconstrictive effect o
f melatonin (10(-5) M). Treatments with melatonin (10(-5) M) did not affect
calcium ionophore A 23187-induced relaxation or 5-hydroxytryptamine-induce
d constriction. The findings indicate that melatonin may potentiate vascula
r tension in human umbilical artery by scavenging endogenous endothelial NO
, but not by inhibiting NO synthesis. However, the NO-scavenging vasoconstr
ictive effect of melatonin may be negligible at physiologic concentrations
and very weak at pharmacologic concentrations below 10(-7) M. (C) 2001 Else
vier Science B.V. All rights reserved.