Imidapril, an angiotensin-converting enzyme inhibitor, inhibits thrombosis via reduction in aortic plasminogen activator inhibitor type-1 levels in spontaneously hypertensive rats.
It is known that angiotensin II (Ang II) exerts an antifibrinolytic effect by stimulating synthesis of plasminogen activator inhibitor type-1 (PAI-1), a specific inhibitor of tissue plasminogen activator (t-PA). The aim of this study was to compare the antithrombotic potency of imidapril, an angiotensin-converting enzyme (ACE) inhibitor, and candesartan, an angiotensin II type 1 (AT1) receptor antagonist, in a model of arterial thrombosis in spontaneously hypertensive rats (SHRs). Oral treatment with 5 mg/kg imidapril 1 h before induction of thrombosis resulted in a significant reduction in thrombus weight, whereas candesartan did not affect thrombus weight under the same treatment conditions. Candesartan lowered blood pressure to the same degree as in the imidapril-treated rats. Imidapril not only reduce the serum and aortic ACE activities, but also reduced aortic PAI-1 protein levels, while candesartan had no effect on theses. These results suggest that imidapril, but not the AT1 receptor antagonist, candesartan, enhances fibrinolysis via a reduction of aortic PAI-1 levels by inhibiting ACE and prevents thrombus formation in SHRs.
Mitsui
T
T
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Chishima
S
S
Odawara
A
A
Ohtani
A
A
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D013927:Thrombosis / Q000517:prevention & control*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D017395:Plasminogen Activator Inhibitor 1; C065166:imidapril