Details

Autor(en) / Beteiligte

• NEWBY, D. E
• WRIGHT, R. A
• LABINJOH, C
• LUDLAM, C. A
• FOX, K. A. A
• BOON, N. A
• WEBB, D. J

Titel

Endothelial dysfunction, impaired endogenous fibrinolysis, and cigarette smoking : A mechanism for arterial thrombosis and myocardial infarction

Ist Teil von

• Circulation (New York, N.Y.), 1999-03, Vol.99 (11), p.1411-1415

Ort / Verlag

Hagerstown, MD: Lippincott Williams & Wilkins

Erscheinungsjahr

1999

Quelle

MEDLINE

Beschreibungen/Notizen

• Effective endogenous fibrinolysis requires rapid release of tissue plasminogen activator (tPA) from the vascular endothelium. Smoking is a known risk factor for arterial thrombosis and myocardial infarction, and it causes endothelial dysfunction. We therefore examined the effects of cigarette smoking on substance P-induced tPA release in vivo in humans. Blood flow and plasma fibrinolytic factors were measured in both forearms of 12 smokers and 12 age- and sex-matched nonsmokers who received unilateral brachial artery infusions of substance P (2 to 8 pmol/min). In both smokers and nonsmokers, substance P caused dose-dependent increases in blood flow and local release of plasma tPA antigen and activity (P<0.001 for all) but had no effect on the local release of plasminogen activator inhibitor type 1. Compared with nonsmokers, increases in forearm blood flow (P=0.03) and release of tPA antigen (P=0.04) and activity (P<0.001) caused by substance P were reduced in smokers. The area under the curve for release of tPA antigen and activity decreased by 51% and 53%, respectively. Cigarette smoking causes marked inhibition of substance P-induced tPA release in vivo in humans. This provides an important mechanism whereby endothelial dysfunction may increase the risk of atherothrombosis through a reduction in the acute fibrinolytic capacity.