title: Melatonin counteracts potentiation by homocysteine of KCL-induced vasoconstriction in human umbilical artery: relation to calcium influx.
abstract: Homocysteinemia is a major and independent risk factor for vascular disease. Oxidative stress is a possible mechanism for homocysteine (HCY)-induced vascular disease. Herein, we evaluated the antioxidant property of melatonin (MLT) in relation to the vasoconstrictive effect of HCY on the human umbilical artery. Helical umbilical arterial strips without endothelium were obtained at elective Cesarean delivery near term. Changes in potassium chloride (KCl)-induced vasoconstriction were measured. Arterial strips were treated with HCY (10 or 100 microM) plus FeSO(4) (10 microM) alone or pretreated with a hydroxyl radical ((*)OH) scavenger, mannitol (20 mM), or MLT (1 or 10 microM). The effect of HCY on the response of arterial strips to external calcium (Ca(2+)) in the presence of KCl (20 mM) was determined. HCY plus FeSO(4) potentiated KCl-induced vasoconstriction in a concentration-dependent manner; pretreatment with mannitol significantly reduced this vasospastic effect. HCY (100 microM) significantly augmented the contractile response to external Ca(2+). MLT (10 microM) significantly suppressed the contractile response to external Ca(2+). These results suggest that HCY potentiates KCl-induced umbilical artery vasoconstriction, in part by increasing Ca(2+) influx in vascular smooth muscle cells via activation of Ca(2+) channels. MLT significantly suppressed the vasoconstrictive effect of HCY, probably by scavenging (*)OH arising from HCY autooxidation.
authors.affiliation: Department of Obstetrics and Gynecology, Kochi Medical School, Kochi, Japan. okataniy@med.kochi-ms.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Okatani
authors.forename: A
authors.initials: A
authors.lastname: Wakatsuki
authors.forename: R J
authors.initials: RJ
authors.lastname: Reiter
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000188:drug therapy; D004347:Drug Interactions; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D006710:Homocysteine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000188:drug therapy; D066298:In Vitro Techniques; D008353:Mannitol / Q000008:administration & dosage / Q000494:pharmacology; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D011189:Potassium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D011247:Pregnancy; D014469:Umbilical Arteries / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D005609:Free Radicals; D006710:Homocysteine; D008353:Mannitol; D011189:Potassium Chloride; D008550:Melatonin