Cigarette smoking impairs bradykinin-stimulated tissue plasminogen activator release in human coronary circulation

Thromb Res. 2007;120(6):791-6. doi: 10.1016/j.thromres.2006.10.024. Epub 2007 Feb 27.

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.

Materials and 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.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Bradykinin / administration & dosage*
  • Bradykinin / metabolism
  • Cardiac Catheterization
  • Coronary Angiography
  • Coronary Circulation / drug effects
  • Coronary Circulation / physiology*
  • Coronary Thrombosis / blood*
  • Coronary Thrombosis / epidemiology
  • Female
  • Fibrinogen / drug effects
  • Fibrinogen / physiology
  • Humans
  • Male
  • Middle Aged
  • Papaverine / administration & dosage
  • Risk Factors
  • Smoking / adverse effects*
  • Smoking / epidemiology
  • Tissue Plasminogen Activator / blood*
  • Vasodilator Agents / administration & dosage*
  • Vasodilator Agents / metabolism

Substances

  • Vasodilator Agents
  • Fibrinogen
  • Papaverine
  • Tissue Plasminogen Activator
  • Bradykinin