Comparison of irbesartan with captopril effects on cardiac hypertrophy andgene expression in heart failure-prone male SHHF/Mcc-fa(cp) rats

Angiotensin-converting enzyme (ACE) inhibitors have proven an effective mea ns to control hypertension and manage cardiac hypertrophy. It is presently unknown if newer specific angiotensin II subtype 1 receptor (AT(1)R) antago nists are as effective or more effective in treating these conditions compa red with ACE inhibitors. There is evidence that these classes of drugs may affect cardiac hypertrophy by different mechanisms. This study compared the effect of irbesartan, an AT1R antagonist, with that of captopril, an ACE i nhibitor, on expression of early genetic markers of cardiac hypertrophy in lean male SHHF/Mcc-fa(cp) rats. SHHF\Mcc-fa(cp) rats (n = 10/group) were gi ven captopril (100 mg/kg/day), irbesartan (50 mg/kg/day), or placebo for 16 weeks. Irbesartan and captopril significantly reduced systolic pressure an d produced similar rightward shifts in the angiotensin I dose-response curv e. Renal renin gene expression was increased 8.6-fold by irbesartan and 17. 7-fold by captopril. The only effect on echocardiographic findings was a si milar decrease in aortic peak velocity, an index of systolic function, by b oth treatments. Early markers of cardiac hypertrophy were significantly att enuated by both drugs. Both drugs produced marked and equivalent reductions in left ventricular atrial natriuretic peptide (ANP) messenger RNA (mRNA) levels compared with controls. This decrease in ANP gene expression was acc ompanied by a decrease in plasma ANP concentration in the treatment groups. The shift from V-1 to V-3 myosin isozymes was similarly decreased in both treatment groups, compared with controls. These data suggest that captopril and irbesartan are similarly effective in controlling expression of genes associated with ventricular hypertrophy in heart failure-prone SHHF/Mcc-fa( cp) rat.