Angiotensin II type 1 receptor blockers reduce tissue factor activity and plasminogen activator inhibitor type-1 antigen in hypertensive patients: a randomized, double-blind, placebo-controlled study

Abstract

Angiotensin II stimulates the expression of tissue factor (TF) and plasminogen activator inhibitor type-1 (PAI-1), and AT1 receptor blockade (ARB) reduces PAI-1 and TF activities in experimental studies. We investigated the effects of ARBs on TF activity, tissue plasminogen activator (tPA), PAI-1 antigen levels, plasma renin activity (PRA) and aldosterone levels in hypertensive patients. Placebo, losartan 100 mg, irbesartan 300 mg, and candesartan 16 mg daily were administered to 122 patients for 2 months. Compared with placebo, ARBs significantly reduced TF activity ( P < 0.001 by ANOVA), and candesartan was the most potent. Compared with placebo or losartan, irbesartan and candesartan significantly lowered plasma levels of PAI-1 antigen ( P < 0.001 by ANOVA) with no differences between the two. Compared with placebo, all ARBs lowered plasma levels of aldosterone ( P = 0.012 by ANOVA) and increased PRA ( P = 0.005 by ANOVA). There were significant correlations between the degree of change in TF activity and PAI-1 antigen levels ( r = 0.458, P < 0.0001) and between the change in TF activity and PRA ( r = −0.296, P = 0.006), but not with the magnitude of reduction in blood pressure following ARB therapy. ARBs significantly reduced TF activity, PAI-1 antigen levels, and aldosterone levels in hypertensive patients. The clinical significance of the varying potency of some ARBs needs to be further investigated.