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.
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 100mg, 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.
Vascular Medicine and Atherosclerosis Unit, Cardiology, Gil Heart Center, Gachon Medical School, 1198 Kuwol-dong, Namdong-gu, Incheon 405-760, Korea. kwangk@ghil.com
Kwang Kon
KK
Koh
Wook-Jin
WJ
Chung
Jeong Yeal
JY
Ahn
Seung Hwan
SH
Han
Woong Chol
WC
Kang
Yiel-Hea
YH
Seo
Tae Hoon
TH
Ahn
In Suck
IS
Choi
Eak Kyun
EK
Shin
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013925:Thromboplastin / Q000032:analysis*
D047228:Angiotensin II Type 1 Receptor Blockers; D017395:Plasminogen Activator Inhibitor 1; D013925:Thromboplastin