Melatonin suppresses homocysteine enhancement of serotonin-induced vasoconstriction in the human umbilical artery.
Hyperhomocysteinemia is a major and independent risk factor for vascular disease. Oxidative stress is a possible mechanism for homocysteine (Hcy)-induced endothelial dysfunction. Herein, we evaluated the antioxidant property of melatonin as related to the vasospastic effect of Hcy on the human umbilical artery. Helical strips of human umbilical arteries with intact endothelium were obtained at elective Caesarean delivery between 37 and 39 wks of gestation. Changes in 5-hydroxytryptamine (5-HT)-induced vasoconstriction were measured. Arterial strips were treated with FeSO4 (10 microM) and Hcy (10 or 100 microM) or pre-treated with a hydroxyl radical (.OH) scavenger (mannitol, 20 mM), a cyclooxygenase inhibitor (indomethacin, 20 microM), nitric oxide (NO) synthesis inhibitor (L-NG-monomethylarginine, LNMA, 200 microM), or melatonin (1 or 10 microM). Hcy potentiated 5-HT-induced constriction in a concentration-dependent manner. Pre-treatment with mannitol significantly suppressed the vasospastic effect of Hcy. LNMA augmented the vasospastic effect of Hcy, but indomethacin did not. Melatonin significantly suppressed the vasospastic effect of Hcy in a concentration-dependent manner. These findings suggest that Hcy potentiates 5-HT-induced vasoconstriction in the human umbilical artery, possibly by suppressing bioavailable NO. Melatonin protects against the vasospastic effect of Hcy, most likely by scavenging.OH arising from Hcy autooxidation.
Okatani
Y
Y
Department of Obstetrics and Gynecology, Kochi Medical School, Kochi, Japan. okataniy@med.kochi-ms.ac.jp
Wakatsuki
A
A
Reiter
R J
RJ
D000975:Antioxidants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005296:Ferrous Compounds / Q000494:pharmacology; D006710:Homocysteine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011247:Pregnancy; D012701:Serotonin / Q000494:pharmacology*; D014469:Umbilical Arteries / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*
D000975:Antioxidants; D004791:Enzyme Inhibitors; D005296:Ferrous Compounds; D006710:Homocysteine; D009569:Nitric Oxide; D012701:Serotonin; C020748:ferrous sulfate; D019001:Nitric Oxide Synthase; D008550:Melatonin