Melatonin suppresses lysophosphatidylcholine enhancement of serotonin-induced vasoconstriction in the human umbilical artery.
We evaluated the antioxidant property of melatonin as related to the vasospastic effect of lysophosphatidylcholine (LPC), a component of oxidized lipoprotein, on the human umbilical artery. Helical sections of umbilical arteries with intact endothelium were obtained at elective cesarean delivery between 37 and 39 weeks of gestation. Changes in 5-hydroxytryptamine (5-HT)-induced vasoconstriction were measured. Arterial sections were treated with LPC alone (15 or 30 microM) or pretreated with an hydroxyl radical (.OH) scavenger (mannitol), a cyclooxygenase inhibitor (indomethacin, 20 microM), nitric oxide (NO) synthesis inhibitor (L-N(G)-monomethylarginine, LNMA, 2 x 10(-4) M), or melatonin (1 or 10 microM). LPC potentiated 5-HT-induced contraction in a concentration-dependent manner. Pretreatment with mannitol significantly suppressed the vasospastic effect of LPC. LNMA augmented the vasospastic effect of LPC, but indomethacin did not. Melatonin significantly suppressed the vasospastic effect of LPC in a concentration-dependent manner. Considering a previous finding that .OH and oxidized low-density lipoprotein decrease NO production in the human umbilical artery, the vasospastic effect of LPC appear to involve suppression of endothelial NO synthesis. Melatonin significantly suppresses the vasospastic effect of LPC, probably by scavenging .OH arising from LPC.
Okatani
Y
Y
Department of Obstetrics and Gynecology, Kochi Medical School, Japan.
Wakatsuki
A
A
Watanabe
K
K
Taniguchi
K
K
Fukaya
T
T
D000328:Adult; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008353:Mannitol / Q000494:pharmacology; D008550:Melatonin / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D012701:Serotonin / Q000494:pharmacology*; D014469:Umbilical Arteries / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D016166:Free Radical Scavengers; D008244:Lysophosphatidylcholines; D019323:omega-N-Methylarginine; D012701:Serotonin; D008353:Mannitol; D008550:Melatonin; D007213:Indomethacin