Comparative effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor antagonism on plasma fibrinolytic balance in humans

Angiotensin-converting enzyme (ACE) inhibition significantly decreases plasminogen activator inhibitor-1 (PAI-1) without altering tissue plasminogen activator (tPA) during activation of the renin-angiotensin-aldosterone system in humans. Because ACE inhibitors and angiotensin II type 1 (AT₁) receptor antagonists differ in their effects on angiotensin II formation and bradykinin degradation, the present study compared the effect of equivalent hypotensive doses of an ACE inhibitor and AT₁ antagonist on fibrinolytic balance. Plasma PAI-1 antigen, tPA antigen, plasma renin activity, and aldosterone were measured in 25 normotensive subjects (19 white, 6 black; 14 men, 11 women; mean age 38.5 ± 1.8 years; mean body mass index 25.3±0.7 kg/m²) during low salt intake alone (10 mmol Na/d), low salt intake + quinapril (40 mg PO bid), and low salt intake + losartan (50 mg PO bid). Compared with low salt alone (systolic blood pressure [BP] 118.8±2.2 mmHg), both quinapril (106.3±2.5 mm Hg, P<0.001) and losartan (105.4±2.8 mm Hg, P<0.001) reduced BP. No statistical difference was found between quinapril and losartan in their BP lowering effect. Losartan (P=0.009), but not quinapril, lowered heart rate. Both drugs significantly lowered aldosterone (P<0.001 versus low salt alone for each); however, this effect was significantly greater for quinapril than for losartan (P<0.001 for quinapril versus losartan). Treatment with quinapril, but not with losartan, was associated with a decrease in both PAI-1 antigen (P=0.03) and activity (P=0.018). PAI-1 activity was lower during treatment with quinapril than with losartan (P=0.015). The average PAI-1 antigen concentration was 13.0±2.0 ng/mL during low salt alone, 10.5 ± 1.6 ng/mL during quinapril treatment, and 12.3 ± 2.1 ng/mL during losartan treatment. In contrast, plasma tPA antigen concentrations were reduced during treatment with losartan (P=0.03) but not with quinapril. This study provides the first evidence that ACE inhibitors and AT₁ antagonists differ in their effects on fibrinolytic balance under conditions of activation of the renin-angiotensin-aldosterone system. Further Studies are needed to address the mechanism for the contrasting effects of these 2 classes of drugs on fibrinolysis and to define the clinical significance of these differences.