Effects of angiotensin converting enzyme and angiotensin II receptor inhibition on impaired fibrinolysis in systemic hypertension

Abnormalities in fibrinolysis have been reported in hypertension. Angiotens in converting enzyme (ACE) inhibitors have been shown to improve altered fi brinolytic balance in hypertensive patients. It has not been documented, ho wever, whether this is due to a decrease in angiotensin II (Ang-II) generat ion or is a consequence of elevated local levels of bradykinin. Accordingly , the aim of this study was to determine the effects of an ACE inhibitor (p erindopril) and an Ang-II receptor antagonist (losartan) on fibrinolytic ki netics. We have examined the serum levels of the plasminogen activator inhibitor ty pe-1 (PAI-1) antigen and activity, tissue plasminogen activator (t-PA) anti gen and activity, soluble thrombomodulin (sTM), and tissue factor pathway i nhibitor (TFPI) before and after reaching the target blood pressure (< 140/ 90 mm Hg) in 13 hypertensive patients receiving perindopril (mean age 40 +/ - 11 years, 6 women, 7 men) and in 12 patients receiving losartan (mean age 38 +/- 9 years, 6 women, 6 men). We also compared the baseline fibrinolyti c activity of hypertensive patients with that of 12 normotensive control pe rsons (mean age 40 +/- 9 years, 6 women, 6 men). The mean basal plasma leve ls of PAI-1 antigen, PAI-1 activity, and sTM were significantly higher in t he hypertensive patients than in normal controls (P < .005). The values of other analytes were similar in both groups. Increased plasma levels of PAI- 1 antigen, PAI-1 activity, and sTM were reduced in patients after they were given perindopril and losartan (P < .005); the reductions in losartan-rece iving group were more pronounced (P < .05). There were no significant effec ts on the plasma levels of t-PA antigen, t-PA activity, and TFPI in patient s receiving the two therapeutic regimens (P > .05). In conclusion chronic hypertension is associated with hypofibrinolysis. The beneficial effect of ACE inhibitors on fibrinolysis seems to be related to the blockade of Ang-II, and increased kinin activity does not appear to pl ay a major role. (C) 1999 American Journal of Hypertension, Ltd.