title: Lipid-soluble smoke particles damage endothelial cells and reduce endothelium-dependent dilatation in rat and man.
abstract: BACKGROUND
  Cigarette smoking is a strong risk factor for vascular disease and known to cause dysfunction of the endothelium. However, the molecular mechanisms involved are still not fully understood.
  
  
  METHODS
  In order to reveal the direct effects of lipid-soluble smoke particles on the endothelium, ring segments isolated from rat mesenteric arteries and human middle cerebral arteries (MCA) obtained at autopsy were incubated for 6 to 48 hrs in the presence of dimethylsulphoxide (DMSO)-soluble particles from cigarette smoke (DSP), i.e. lipid-soluble smoke particles. The endothelial microstructure was examined by transmission electron microscopy. The endothelial function was evaluated by acetylcholine (ACh)-induced endothelium-dependent vasodilatation, using a sensitive myograph.
  
  
  RESULTS
  After DSP treatment, the arterial endothelium was swollen and loosing its attachment. In functional tests, the total ACh-induced dilatation, the nitric oxide (NO)-mediated and the endothelium-derived hyperpolarization factor (EDHF)-mediated dilatations were significantly decreased by DSP in a time- and concentration-dependent manner (p < 0.05). Nicotine, an important compound in cigarette smoke had, in an equivalent concentration as in DSP, no such effects (p > 0.05). Similar results were obtained in the human MCA.
  
  
  CONCLUSIONS
  Thus, we demonstrate that the lipid-soluble smoke particles, but not nicotine, caused damage to arterial endothelium and reduced the endothelium-dependent dilatation in man and rat.
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, PR China. zhangjiyan1978@163.com
authors.forename: Jin-Yan
authors.initials: JY
authors.lastname: Zhang
authors.forename: Yong-Xiao
authors.initials: YX
authors.lastname: Cao
authors.forename: Cang-Bao
authors.initials: CB
authors.lastname: Xu
authors.forename: Lars
authors.initials: L
authors.lastname: Edvinsson
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008055:Lipids / Q000032:analysis* / Q000737:chemistry; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012906:Smoke / Q000032:analysis*; D012995:Solubility; D013997:Time Factors; D014026:Nicotiana / Q000737:chemistry / Q000633:toxicity*; D014664:Vasodilation
chemical_list: D001685:Biological Factors; D008055:Lipids; D012906:Smoke; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D004121:Dimethyl Sulfoxide