• C Labinjoh, D E Newby, M P Pellegrini, N R Johnston, N A Boon, and D J Webb.
• Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, United Kingdom.
• J. Am. Coll. Cardiol. 2001 Nov 1; 38 (5): 1402-8.

ObjectivesThe aim of the present study was to determine the effect of angiotensin-converting enzyme (ACE) inhibition on the local stimulated release of tissue plasminogen activator (t-PA) from the endothelium.BackgroundAngiotensin-converting enzyme inhibitor therapy may exert a beneficial effect on the endogenous fibrinolytic balance.MethodsBlood flow and plasma fibrinolytic factors were measured in both forearms of eight healthy males who received unilateral brachial artery infusions of the endothelium-dependent vasodilators substance P (2 to 8 pmol/min) and bradykinin (100 to 1,000 pmol/min), and the endothelium-independent vasodilator sodium nitroprusside (2 to 8 microg/min). These measurements were performed on each of three occasions following one week of matched placebo, quinapril 40 mg or losartan 50 mg daily administered in a double-blind randomized crossover design.ResultsSodium nitroprusside, substance P and bradykinin produced dose-dependent increases in the blood flow of infused forearm (analysis of variance [ANOVA], p < 0.001 for all). Although sodium nitroprusside did not affect plasma t-PA concentrations, they were increased dose-dependently in the infused 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 treatment 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 interaction), whereas the substance P response was unaffected.ConclusionsWe have shown a selective and marked augmentation of bradykinin-induced t-PA release during ACE inhibition. These findings suggest that the beneficial clinical and vascular effects of ACE inhibition may, in part, be mediated through local augmentation of bradykinin-induced t-PA release.

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