title: Cigarette smoke-induced endothelium dysfunction: role of superoxide anion.
abstract: OBJECTIVE
  Cigarette smoking is strongly associated with coronary artery disease and atherosclerosis. While smoking has been shown to impair endothelium-dependent vasorelaxation, the mechanisms involved are not completely understood. We investigated the role of superoxide anion and vasoconstricting prostanoids in cigarette smoke induced endothelial dysfunction.
  
  
  METHODS
  Endothelial function was assessed in rat aortic rings exposed to cigarette smoke-treated Krebs buffer, by measuring agonist stimulated endothelium-dependent vasorelaxation. Treatment with superoxide dismutase (SOD) as well as ifetroban, thromboxane A2/prostaglandin endoperoxide H2 (TxA2/PGH2) receptor blocker and indomethacin (cyclooxygenase inhibitor) was used to investigate the role of superoxide anion and vasoconstricting eicosanoids on cigarette smoke-induced endothelial dysfunction. The effect of cigarette smoke on endothelial nitric oxide synthase (eNOS) catalytic activity was measured by conversion of L-arginine to L-citrulline in rat aortas and rat endothelial cell homogenates supplemented with eNOS cofactors.
  
  
  RESULTS
  Relaxations to receptor-dependent agonists, acetylcholine and adenosine diphosphate (ADP), as well as to a receptor-independent agonist, A23187 (Ca2+ ionophore) were significantly impaired by cigarette smoke. Cigarette smoke did not impair relaxations to sodium nitroprusside, indicating preserved guanylate cyclase activity. Further, cigarette smoke did not affect eNOS catalytic activity in homogenates from either endothelial cells or aortas previously exposed to cigarette-smoketreated Krebs buffer. Treatment with SOD or ifetroban and in a lesser degree by indomethacin prevented cigarette-smoke-induced endothelial dysfunction.
  
  
  CONCLUSIONS
  Taken together, our results suggest that cigarette smoking causes an increase in vascular superoxide production which results in decreased nitric oxide (NO) bioactivity and concomitantly increases production of cyclooxygenase dependent and independent vasoconstricting eicosanoids.
authors.affiliation: Veterans Affairs Medical Center and Department of Medicine, University of Minnesota Medical School, Minneapolis 55417, USA. raijx001@maroon.tc.umn.edu
authors.forename: L
authors.initials: L
authors.lastname: Raij
authors.forename: E G
authors.initials: EG
authors.lastname: DeMaster
authors.forename: E A
authors.initials: EA
authors.lastname: Jaimes
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010947:Plants, Toxic; D051381:Rats; D017207:Rats, Sprague-Dawley; D012906:Smoke / Q000009:adverse effects*; D013481:Superoxides / Q000378:metabolism*; D014026:Nicotiana; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D012906:Smoke; D014665:Vasodilator Agents; D013481:Superoxides; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat