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Melatonin suppresses homocysteine enhancement of serotonin‐induced vasoconstriction in the human umbilical artery
Author(s) -
Okatani Y.,
Wakatsuki A.,
Reiter R.J.
Publication year - 2001
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1034/j.1600-079x.2001.310308.x
Subject(s) - melatonin , vasoconstriction , endocrinology , nitric oxide , medicine , endothelial dysfunction , homocysteine , oxidative stress , umbilical artery , vasodilation , endothelium , pharmacology , chemistry , biology , gestation , pregnancy , genetics
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 FeSO 4 (10 μM) and Hcy (10 or 100 μM) or pre‐treated with a hydroxyl radical (·OH) scavenger (mannitol, 20 mM), a cyclooxygenase inhibitor (indomethacin, 20 μM), nitric oxide (NO) synthesis inhibitor (L‐N G ‐monomethylarginine, LNMA, 200 μM), or melatonin (1 or 10 μM). 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.