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BACKROUND: The renin-angiotensin-aldosterone system plays a central role in fibrinolysis. Activation of the RAAS stimulates the expression of plasminogen activator inhibitor (PAI-1), which can be directly implicated in the pathophysiology of thromboembolic events. Our primary aims were, 1) to measure the effect of acute RAAS activation on plasma levels of PAI-1, and 2) to measure the inhibitory effect of an ACE inhibitor alone, versus a combination of an ACE inhibitor and aldosterone blocker on the usual increase in PAI-1 usually observed.
METHODS: In the current prospective in vivo study, RAAS was activated by means of phlebotomy, an effective, physiologic means of RAAS activation. Seventeen voluntary pre-hypertensive 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, 12/17 donors were randomly assigned to receive enalapril (5 mg) or the combination of enalapril (5 mg) plus spironolactone (25 mg), beginning three days prior to phlebotomy and 5 were assigned as controls who received no medications.
RESULTS: 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 to the initial phlebotomy, but it did not return to baseline levels. The observed mean reduction in PAI-1 level was greater for the subjects receiving both ACE and aldosterone inhibition.
CONCLUSION: Enalapril and 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.