A Dynamic Comparative Study Concerning the Effects of Angiotensin-Converting Enzyme Inhibitors and Aldosterone Receptor Blockers on the Fibrinolytic System

Abstract

The renin—angiotensin—aldosterone system (RAAS) plays a central role in fibrinolysis. Activation of the RAAS stimulates the expression of plasminogen activator inhibitor-1 (PAI-1), which can be directly implicated in the pathophysiology of thromboembolic events. Our primary aims were to measure (1) the effect of acute RAAS activation on plasma levels of PAI-1, and (2) the inhibitory effect of an angiotensin-converting enzyme (ACE) inhibitor alone, versus a combination of an ACE inhibitor and aldosterone blockade on the increase in PAI-1 usually observed. In the current prospective in vivo study, RAAS was activated by means of phlebotomy, an effective, physiologic means of RAAS activation. Seventeen voluntary prehypertensive, but otherwise healthy, blood donors were included in this study. Renin and PAI-1 levels were measured before and after initial phlebotomy. At the time of the second phlebotomy, 12 of 17 donors randomly were assigned to receive enalapril (5 mg) or a combination of enalapril (5 mg) plus spironolactone (25 mg), beginning 3 days before phlebotomy, and 5 were assigned to be controls, receiving no medications. Plasma renin and PAI levels were significantly increased following initial phlebotomy. At the time of the second phlebotomy, plasma PAI-1 activity was reduced significantly, as compared with the initial phlebotomy, but it did not return to baseline levels. The observed mean reduction in PAI-1 level was greater among the subjects who received both ACE and aldosterone inhibition. Enalapril and the combination of enalapril plus spironolactone efficiently reduce PAI-1 levels, but the reductions are more pronounced with the combined regimen. However, neither treatment appears sufficient to return PAI-1 activity to baseline levels.