Potentiation of bradykinin-induced tissue plasminogen activator release byangiotensin-converting enzyme inhibition

Objectives The aim of the present study was to determine the effect of angi otensin-converting enzyme (ACE) inhibition on the local stimulated release of tissue plasminogen activator (t-PA) from the endothelium. Background Angiotensin-converting enzyme inhibitor therapy may exert a bene ficial effect on the endogenous fibrinolytic balance. Methods Blood flow and plasma fibrinolytic factors were measured in both fo rearms of eight healthy males who received unilateral brachial artery infus ions of the endothelium-dependent vasodilators substance P (2 to 8 pmol/min ) and bradykinin (100 to 1,000 pmol/min), and the endothelium-independent v asodilator sodium nitroprusside (2 to 8 mug/min). These measurements were p erformed on each of three occasions following one week of matched placebo, quinapril 40 mg or losartan 50 mg daily administered in a double-blind rand omized crossover design. Results Sodium nitroprusside, substance P and bradykinin produced dose-depe ndent increases in the blood flow of infused forearm (analysis of variance [ANOVA], p<0.001 for all). Although sodium nitroprusside did not affect pla sma t-PA concentrations, they were increased dose-dependently in the infuse d forearm by substance P and bradykinin infusion (ANOVA, p<0.001 for both). Bradykinin-induced release of active t-PA was more than doubled during tre atment with quinapril in comparison to placebo or losartan (two-way ANOVA: p<0.003 for treatment group, p<0.001 for t-PA response and p=ns for interac tion), whereas the substance P response was unaffected. Conclusions We have shown a selective and marked augmentation of bradykinin -induced t-PA release during ACE inhibition. These findings suggest that th e beneficial clinical and vascular effects of ACE inhibition may, in part, be mediated through local augmentation of bradykinin-induced t-PA release. (J Am Coll Cardiol 2001;38:1402-8) (C) 2001 by the American College of Card iology.