Melatonin counteracts potentiation by homocysteine of kcl-induced vasoconstriction in human umbilical artery: relation to calcium influx

Alternative Medicine Review, April, 2001 by Y Okatani, A Wakatsuki

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 ?M) plus FeSO(4) (10 ?M) alone or pretreated with a hydroxyl radical ((*)OH) scavenger, mannitol (20 mM), or MLT (1 or 10 ?M). 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 ?M) significantly augmented the contractile response to external Ca(2 ). MLT (10 ?M) 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.

Okatani Y, Wakatsuki A, Reiter RJ. Biochem Biophys Res Commun 2001;280:940-944.