Melatonin counteracts potentiation by lysophosphatidylcholine of serotonin-induced vasoconstriction in human umbilical artery: relation to calcium influx.
We evaluated mechanisms underlying the antioxidant property of melatonin as related to vasospastic effects in the human umbilical artery from lysophosphatidylcholine (LPC), a component of oxidized lipoprotein. Helical sections of umbilical artery without endothelium were obtained at elective cesarean delivery between 37 and 39 wk of gestation. Changes in 5-hydroxytryptamine (5-HT)-induced vasoconstriction were measured. Arterial sections were treated with LPC (15 or 30 microM) alone or pretreated with a hydroxyl radical (.OH) scavenger, mannitol (20 mM), an H2O2 scavenger, catalase (1,200 U/mL), or melatonin (0.1 or 1.0 microM). The effect of LPC on the response of arterial sections to external calcium in the presence of KCl (20 mM) was determined. LPC potentiated 5-HT-induced vasoconstriction in a concentration-dependent manner; pretreatment with mannitol or catalase significantly reduced this vasospastic effect. LPC (30 microM) significantly augmented the contractile response to external calcium. Melatonin (1.0 microM) pretreatment significantly suppressed the contractile response to external calcium. The results suggest that LPC potentiates 5-HT-induced umbilical artery vasoconstriction, in part by increasing the calcium influx into smooth muscle cells via activation of voltage-dependent calcium channels. Given a previous finding, the vasospastic effect of LPC on the umbilical artery also appears to involve the suppression of endothelial nitric oxide production. Melatonin significantly suppresses the vasospastic effect of LPC, probably by scavenging .OH arising from LPC.
Department of Obstetrics and Gynecology, Kochi Medical School, Oko, Nankoku, Japan.
Y
Y
Okatani
A
A
Wakatsuki
K
K
Watanabe
K
K
Taniguchi
T
T
Fukaya
D000975:Antioxidants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D008244:Lysophosphatidylcholines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008550:Melatonin / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D014469:Umbilical Arteries / Q000187:drug effects*; D014661:Vasoconstriction / Q000502:physiology*
D000975:Antioxidants; D015220:Calcium Channels; D016166:Free Radical Scavengers; D008244:Lysophosphatidylcholines; D012701:Serotonin; D008550:Melatonin; D002118:Calcium