title: Attenuation by melatonin of human umbilical arterial vasoconstriction induced by lysophosphatidylcholine.
abstract: 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 were obtained from healthy pregnant women who were delivered between 37 and 39 wk of gestation. Changes in maximal tension induced by KCl were measured in arterial sections having intact endothelium. Sections were treated with LPC alone (15 or 30 microM), or were pretreated either with a hydrogen peroxide (H2O2) scavenger (catalase, 1,200 U/mL), a hydroxyl radical scavenger (mannitol, 30 mM), a nitric oxide (NO) synthesis inhibitor (L-N(G)-monomethyl arginine, LNMA, 2 x 10(-4) M) or melatonin (1 or 10 microM). The effect of LPC (30 microM) on the vasorelaxation induced by 5-hydroxytryptamine (5-HT) was also determined, with or without melatonin pretreatment (10 microM). LPC potentiated vascular tension in a concentration-dependent manner. Pretreatment with LNMA significantly suppressed this vasospastic effect of LPC. Pretreatment with catalase or mannitol significantly reduced the vasospastic effect of LPC. Melatonin significantly lessened the vasospastic effect of LPC in a concentration-dependent manner. Pretreatment with LPC significantly inhibited the relaxation induced by 5-HT. Treatment with melatonin prior to LPC exposure significantly restored the relaxation induced by 5-HT. Results suggest that LPC potentiates vascular tension in human umbilical artery, perhaps by suppressing the endothelial synthesis of NO. Melatonin significantly suppressed the vasospastic effect of LPC. This agent probably scavenges the hydroxyl radicals arising from LPC.
authors.affiliation: Department of Obstetrics and Gynecology, Kochi Medical School, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Okatani
authors.forename: A
authors.initials: A
authors.lastname: Wakatsuki
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: T
authors.initials: T
authors.lastname: Fukaya
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008353:Mannitol / Q000494:pharmacology; D008550:Melatonin / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011189:Potassium Chloride / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D014469:Umbilical Arteries / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D008244:Lysophosphatidylcholines; D019323:omega-N-Methylarginine; D012701:Serotonin; D008353:Mannitol; D011189:Potassium Chloride; D002374:Catalase; D019001:Nitric Oxide Synthase; D008550:Melatonin