Arsenite increases vasoconstrictor reactivity in rat blood vessels: role of endothelial nitric oxide function.
Arsenite has been shown to inhibit endothelium-dependent, nitric oxide-mediated vasodilation in vitro. This study investigated the effects of arsenite on vascular reactivity in vivo. Saline or sodium arsenite (6 mg kg-1) was administered intravenously in Wistar-Kyoto rats for 4 h. As compared to saline, arsenite significantly increased vasoconstrictor responses to phenylephrine in both rat isolated aorta and renal arteries examined in tissue bath. This change was diminished after preincubation of the tissues with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, which increased phenylephrine-induced vasoconstriction to a similar extent as arsenite. In contrast, acetylcholine-induced vasodilation, mediated by nitric oxide in the aorta and by an endothelium-derived hyperpolarizing factor in renal arteries, was not affected by arsenite. Arsenite induced expression of heat shock proteins Hsp72, Hsp32, and Hsp90, but endothelial nitric oxide synthase expression was not changed. The effects of arsenite on vasoreactivity were unlikely to be mediated by heat shock protein induction, because blockade of heat shock protein induction had little effect on the increased vasoconstriction in vessels from arsenite-treated animals. Our study suggests that in vivo arsenic treatment increases vasoconstrictor reactivity by compromising basal endothelial nitric oxide function, which is not caused by altered endothelial nitric oxide synthase expression.
Bilszta
Justin L C
JL
Howard Florey Institute, University of Melbourne, Victoria, Australia.
Dusting
Gregory J
GJ
Jiang
Fan
F
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D018053:Arsenites / Q000633:toxicity*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D004785:Environmental Pollutants / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D012077:Renal Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D018053:Arsenites; D004785:Environmental Pollutants; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D010656:Phenylephrine; D052250:Nitric Oxide Synthase Type III; C015001:arsenite; D000109:Acetylcholine