title: Copper induces vasorelaxation and antagonizes noradrenaline-induced vasoconstriction in rat mesenteric artery.
abstract: OBJECTIVE
  Copper is an essential trace element for normal cellular function and contributes to critical physiological or pathological processes. The aim of the study was to investigate the effects of copper on vascular tone of rat mesenteric artery and compare the effects of copper on noradrenaline (NA) and high K(+) induced vasoconstriction.
  
  
  METHODS
  The rat mesenteric arteries were isolated and the vessel tone was measured by using multi wire myograph system in vitro. Blood pressure of carotid artery in rabbits was measured by using physiological data acquisition and analysis system in vivo.
  
  
  RESULTS
  Copper dose-dependently blunted NA-induced vasoconstriction of rat mesenteric artery. Copper-induced vasorelaxation was inhibited when the vessels were pretreated with NG-nitro-L-arginine methyl ester (L-NAME). Copper did not blunt high K(+)-induced vasoconstriction. Copper preincubation inhibited NA-evoked vasoconstriction and the inhibition was not affected by the presence of L-NAME. Copper preincubation showed no effect on high K(+)-evoked vasoconstriction. Copper chelator diethyldithiocarbamate trihydrate (DTC) antagonized the vasoactivity induced by copper in rat mesenteric artery. In vivo experiments showed that copper injection (iv) significantly decreased blood pressure of rabbits and NA or DTC injection (iv) did not rescue the copper-induced hypotension and animal death.
  
  
  CONCLUSIONS
  Copper blunted NA but not high K(+)-induced vasoconstriction of rat mesenteric artery. The acute effect of copper on NA-induced vasoconstriction was depended on nitric oxide (NO), but the effect of copper pretreatment on NA-induced vasoconstriction was independed on NO, suggesting that copper affected NA-induced vasoconstriction by two distinct mechanisms.
authors.affiliation: Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, P.R.China.
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Wang
authors.forename: Chao-Wei
authors.initials: CW
authors.lastname: Hu
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Liu
authors.forename: Hong-Chao
authors.initials: HC
authors.lastname: Jiang
authors.forename: Rong
authors.initials: R
authors.lastname: Huo
authors.forename: De-Li
authors.initials: DL
authors.lastname: Dong
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology*; D004050:Ditiocarb / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D002614:Chelating Agents; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D003300:Copper; D004050:Ditiocarb; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine