Differential effects of imidapril and candesartan cilexetil on plasminogen activator inhibitor-1 expression induced by prolonged inhibition of nitric oxide synthesis in rat hearts

We investigated effects of the angiotensin-converting enzyme (ACE) inhibitor imidapril and the angiotensin II type 1 (AT ₁) antagonist candesartan cilexetil on cardiac plasminogen activator inhibitor-1 (PAI-1) expression in rats. Cardiac PAI-1 mRNA levels were increased after a 7-day treatment with the nitric oxide (NO) synthesis inhibitor N(ω)-nitro-L- arginine methyl ester (L-NAME). PAI-1 immunoreactivity was increased in the coronary arteries. Treatment with imidapril significantly prevented the L- NAME-induced increase in the gene expression and immunoreactivity of PAI-1, but candesartan cilexetil showed no such effect. This study provides the first evidence of differential effects of ACE inhibition and AT ₁ antagonism on cardiac PAI-1 expression in vivo.