Protective effect of melatonin against homocysteine-induced vasoconstriction of human umbilical artery

Yuji Okatani, Akihiko Wakatsuki, Russel J. Reiter

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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 (MLT) in relation to the vasoconstrictive effect of Hcy on the human umbilical artery. In an initial experiment in a cell-free system, a micromolar concentration of iron was found to catalyze oxygen-dependent oxidation of Hcy. MLT (10 or 100 μM) did not affect oxygen-dependent oxidation of Hcy. Next, smooth muscle contraction induced by prostaglandin F(2α) (10 μM) was measured in arterial strips. Hcy (10 to 500 μM) increased this vascular tension in a concentration-dependent manner (P < 0.0001). Addition of Fe2+ (10 μM) significantly potentiated the Hcy effect. Removal of endothelium (P < 0.05), pretreatment with a nitric oxide (NO) synthesis inhibitor (L-N(G)-monomethylarginine, 200 μM, P < 0.001), or pretreatment with a hydroxyl radical (.OH) scavenger (mannitol, 10 mM, P < 0.001) significantly attenuated contraction potentiated by Hcy plus Fe2+. At a much lower concentration than mannitol, MLT (1 to 100 μM) significantly reduced the contractile effect of Hcy and Fe2+ in a concentration-dependent manner. Hcy plus Fe2+ significantly impaired calcium ionophore A 23187-induced relaxation (P < 0.0001), while MLT restored this relaxation in a concentration-dependent manner. These findings suggest that Hcy potentiates vascular tension in human umbilical artery, possibly by suppressing bioavailable NO. MLT protects against the vasoconstrictive effect of Hcy, most likely by scavenging .OH arising from Hcy autooxidation. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)470-475
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume277
Issue number2
DOIs
StatePublished - Oct 22 2000

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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