Melatonin suppresses homocysteine enhancement of serotonin-induced vasoconstriction in the human umbilical artery

Y. Okatani, A. Wakatsuki, R. J. Reiter

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Abstract

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 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-NG-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.

Original languageEnglish (US)
Pages (from-to)242-247
Number of pages6
JournalJournal of pineal research
Volume31
Issue number3
DOIs
StatePublished - Oct 9 2001

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Keywords

  • Free radical
  • Homocysteine
  • Melatonin
  • Nitric oxide
  • Umbilical artery

ASJC Scopus subject areas

  • Endocrinology

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