title: Arsenic-induced dysfunction in relaxation of blood vessels.
abstract: Several epidemiological studies have suggested that exposure to arsenic is strongly correlated with the development of cardiovascular diseases such as hypertension. To determine whether arsenic affects vasomotor tone in blood vessels, we investigated the effect of arsenic on vasorelaxation using isolated rat aortic rings in an organ-bath system. Treatment with arsenite inhibited acetylcholine-induced relaxation of the aortic rings in a concentration-dependent manner, whereas several other arsenic species did not have any effect. Consistent with these findings, the levels of guanosine 3',5'-cyclic monophosphate (cGMP) in the aortic rings were significantly reduced by arsenite treatment. In cultured human aortic endothelial cells, treatment with arsenite resulted in a concentration-dependent inhibition of endothelial nitric oxide synthase (eNOS). In addition, higher concentrations of arsenite decreased the relaxation induced by sodium nitroprusside (an NO donor) and 8-Br-cGMP (a cGMP analog) in aortic rings without endothelium. These in vitro results indicate that arsenite is capable of suppressing relaxation in blood vessels by inhibiting eNOS activity in endothelial cells and by impairing the relaxation machinery in smooth muscle cells. In vivo studies revealed that the reduction of blood pressure by acetylcholine infusion was significantly suppressed after arsenite was administered intravenously to rats. These data suggest that an impairment of vasomotor tone due to arsenite exposure may be a contributing factor in the development of cardiovascular disease.
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, Korea.
authors.forename: Moo-Yeol
authors.initials: MY
authors.lastname: Lee
authors.forename: Byung-In
authors.initials: BI
authors.lastname: Jung
authors.forename: Seung-Min
authors.initials: SM
authors.lastname: Chung
authors.forename: Ok-Nam
authors.initials: ON
authors.lastname: Bae
authors.forename: Joo-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Jung-Duck
authors.initials: JD
authors.lastname: Park
authors.forename: Ji-Sun
authors.initials: JS
authors.lastname: Yang
authors.forename: Hyomin
authors.initials: H
authors.lastname: Lee
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Chung
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001151:Arsenic / Q000009:adverse effects*; D018053:Arsenites / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000139:chemically induced*; D008297:Male; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D018053:Arsenites; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; C015001:arsenite; D001151:Arsenic