title: Nuciferine relaxes rat mesenteric arteries through endothelium-dependent and -independent mechanisms.
abstract: OBJECTIVE
  Nuciferine, a constituent of lotus leaf, is an aromatic ring-containing alkaloid, with antioxidative properties. We hypothesize nuciferine might affect vascular reactivity. This study aimed at determining the effects of nuciferine on vasomotor tone and the underlying mechanism
  
  
  METHODS
  Nuciferine-induced relaxations in rings of rat main mesenteric arteries were measured by wire myographs. Endothelial NOS (eNOS) was determined by immunoblotting. Intracellular NO production in HUVECs and Ca(2+) level in both HUVECs and vascular smooth muscle cells (VSMCs) from rat mesenteric arteries were assessed by fluorescence imaging.
  
  
  RESULTS
  Nuciferine induced relaxations in arterial segments pre-contracted by KCl or phenylephrine. Nuciferine-elicited arterial relaxations were reduced by removal of endothelium or by pretreatment with the eNOS inhibitor L-NAME or the NO-sensitive guanylyl cyclase inhibitor ODQ. In HUVECs, the phosphorylation of eNOS at Ser(1177) and increase in cytosolic NO level induced by nuciferine were mediated by extracellular Ca(2+) influx. Under endothelium-free conditions, nuciferine attenuated CaCl2-induced contraction in Ca(2+)-free depolarizing medium. In the absence of extracellular calcium, nuciferine relieved the vasoconstriction induced by phenylephrine and the addition of CaCl2. Nuciferine also suppressed Ca(2+) influx in Ca(2+)-free K(+)-containing solution in VSMCs.
  
  
  CONCLUSIONS
  Nuciferine has a vasorelaxant effect via both endothelium-dependent and -independent mechanisms. These results suggest that nuciferine may have a therapeutic effect on vascular diseases associated with aberrant vasoconstriction.
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, China.|Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Vascular Medicine, School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Wai San
authors.initials: WS
authors.lastname: Cheang
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, China.|School of Public Health, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Yang
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Baochang
authors.initials: B
authors.lastname: Lai
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Meiqian
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Jiahua
authors.initials: J
authors.lastname: Ni
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Zihui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of Vascular Medicine, School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, China.|Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Nanping
authors.initials: N
authors.lastname: Wang
mesh_terms: D000818:Animals; D001060:Aporphines / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001060:Aporphines; D014665:Vasodilator Agents; D052250:Nitric Oxide Synthase Type III; D002118:Calcium; C008692:nuciferine