title: Cigarette smoking impairs bradykinin-stimulated tissue plasminogen activator release in human coronary circulation.
abstract: BACKGROUND
  Cigarette smoking is a major risk factor for acute coronary thrombosis. Bradykinin (BK) can induce the release of tissue plasminogen activator (tPA) from the coronary vasculature. The purpose of this study was to investigate whether smoking reduces BK-stimulated tPA release in human coronary circulation.
  
  
  METHODS
  We examined two groups: 20 current smokers and 19 nonsmokers. By cardiac catheterization, graded doses of BK (0.2, 0.6 and 2.0 microg/min) and papaverine (PA) (12 mg) were administered into the coronary artery. Coronary blood flow (CBF) was measured using a Doppler flow wire. Blood samples from the aorta (Ao) and coronary sinus (CS) were assayed.
  
  
  RESULTS
  BK increased both coronary artery diameter (CD) and CBF to a similar extent in the two groups. The net coronary tPA release was dose-dependently increased by BK in the two groups, but the degree of this increase in current smokers was significantly lower than that in nonsmokers. BK did not change plasminogen activator inhibitor type 1 (PAI 1) levels in either group. PA did not alter either tPA or PAI-1 levels in either group.
  
  
  CONCLUSIONS
  These results suggest that cigarette smoking deteriorates coronary fibrolytic activity, independent of changes in CBF. These findings can at least partly explain the higher risk of coronary thrombosis in smokers.
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Seta, Otsu 520-2192, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takashima
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakae
authors.forename: Tetsunobu
authors.initials: T
authors.lastname: Yamane
authors.forename: Minoru
authors.initials: M
authors.lastname: Horie
mesh_terms: D001920:Bradykinin / Q000008:administration & dosage* / Q000378:metabolism; D006328:Cardiac Catheterization; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003328:Coronary Thrombosis / Q000097:blood* / Q000453:epidemiology; D005260:Female; D005340:Fibrinogen / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010208:Papaverine / Q000008:administration & dosage; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology; D010959:Tissue Plasminogen Activator / Q000097:blood*; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D014665:Vasodilator Agents; D005340:Fibrinogen; D010208:Papaverine; D010959:Tissue Plasminogen Activator; D001920:Bradykinin