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

Y. Okatani, A. Wakatsuki, Russel J Reiter

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 - 2001

Fingerprint

Umbilical Arteries
Homocysteine
Melatonin
Vasoconstriction
Serotonin
Mannitol
Indomethacin
Nitric Oxide
Hyperhomocysteinemia
Cyclooxygenase Inhibitors
Vascular Diseases
Constriction
Hydroxyl Radical
Endothelium
Oxidative Stress
Antioxidants
Pregnancy

Keywords

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

ASJC Scopus subject areas

  • Endocrinology

Cite this

Melatonin suppresses homocysteine enhancement of serotonin-induced vasoconstriction in the human umbilical artery. / Okatani, Y.; Wakatsuki, A.; Reiter, Russel J.

In: Journal of Pineal Research, Vol. 31, No. 3, 2001, p. 242-247.

Research output: Contribution to journalArticle

@article{677102386fcd4eb38a03fb13af4356c8,
title = "Melatonin suppresses homocysteine enhancement of serotonin-induced vasoconstriction in the human umbilical artery",
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.",
keywords = "Free radical, Homocysteine, Melatonin, Nitric oxide, Umbilical artery",
author = "Y. Okatani and A. Wakatsuki and Reiter, {Russel J}",
year = "2001",
doi = "10.1034/j.1600-079X.2001.310308.x",
language = "English (US)",
volume = "31",
pages = "242--247",
journal = "Journal of Pineal Research",
issn = "0742-3098",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Melatonin suppresses homocysteine enhancement of serotonin-induced vasoconstriction in the human umbilical artery

AU - Okatani, Y.

AU - Wakatsuki, A.

AU - Reiter, Russel J

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

KW - Free radical

KW - Homocysteine

KW - Melatonin

KW - Nitric oxide

KW - Umbilical artery

UR - http://www.scopus.com/inward/record.url?scp=0034813694&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034813694&partnerID=8YFLogxK

U2 - 10.1034/j.1600-079X.2001.310308.x

DO - 10.1034/j.1600-079X.2001.310308.x

M3 - Article

C2 - 11589759

AN - SCOPUS:0034813694

VL - 31

SP - 242

EP - 247

JO - Journal of Pineal Research

JF - Journal of Pineal Research

SN - 0742-3098

IS - 3

ER -