Weak vasoconstrictor activity of melatonin in human umbilical artery: relation to nitric oxide-scavenging action.
We evaluated the nitric oxide (NO)-scavenging property of melatonin, demonstrated in a recent in vitro study, on vascular reactivity in the human umbilical artery. Helical sections of human umbilical artery were prepared following elective Cesarean deliveries near term. Changes in maximal tension induced by prostaglandin F(2 alpha)(5 x 10(-5) M) were measured in artery sections with an intact endothelium. Melatonin at concentrations higher than 10(-6) M increased prostaglandin F(2 alpha)-induced vascular tension. The vasospastic effect of melatonin was much less than that of L-N(G)-monomethylarginine (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 melatonin concentrations of 10(-8), 10(-7), 10(-6), and 10(-5) M, respectively). Removal of the endothelium significantly reduced the vasoconstrictive effect of melatonin. Treatment with L-NMA (2 x 10(-4) M) prior to addition of prostaglandin F(2 alpha) also significantly reduced the vasoconstrictive effect of melatonin (10(-5) M). Treatments with melatonin (10(-5) M) did not affect calcium ionophore A 23187-induced relaxation or 5-hydroxytryptamine-induced constriction. The findings indicate that melatonin may potentiate vascular tension in human umbilical artery by scavenging endogenous endothelial NO, but not by inhibiting NO synthesis. However, the NO-scavenging vasoconstrictive effect of melatonin may be negligible at physiologic concentrations and very weak at pharmacologic concentrations below 10(-7) M.
Okatani
Y
Y
Department of Obstetrics and Gynecology, Kochi Medical School, Oko, Nankoku, 783-8505, Kochi, Japan. okataniy@med.kochi-ms.ac.jp
Wakatsuki
A
A
Watanabe
K
K
Taniguchi
K
K
Fukaya
T
T
D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008550:Melatonin / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014469:Umbilical Arteries / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*; D019323:omega-N-Methylarginine
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D019323:omega-N-Methylarginine; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D008550:Melatonin