Angiotensin type 1 receptor antagonism with irbesartan inhibits ventricular hypertrophy and improves diastolic function in the remodeling post-myocardial infarction ventricle

To evaluate the role of angiotensin II (AII) on diastolic function during p ost-myocardial infarction (MI) ventricular remodeling, coronary ligation or sham operation was performed in male Sprague-Dawley rats. Experimental ani mals were maintained on either irbesartan, a selective AT(1)-receptor antag onist, or no treatment. Measurement of cardiac hypertrophy, diastolic funct ion, and sarcoendoplasmic reticulum adenosine triphosphatase (ATPase; SERCA ) and phospholamban (PLB) gene expression was assessed at 6 weeks after MI. Myocardial infarction caused a significant increase in myocardial mass and left ventricular (LV) filling pressure, whereas LV systolic pressure and dP/dt were reduced. The time constant of isovolumic relaxation (tau) was ma rkedly prolonged after MI. Post-MI hypertrophy was associated with substant ial increases in the messenger RNA (mRNA) expression of atrial natriuretic peptide (ANP), but no significant changes in SERCA or PLB levels. Although irbesartan treatment did not significantly alter post-MI LV systolic or fil ling pressures, it nevertheless effectively decreased ventricular hypertrop hy, improved tau, and normalized ANP expression. These results demonstrate that AT(1)-receptor antagonism has important effects on myocardial hypertro phy and ANP gene expression, which are independent of ventricular loading c onditions. In addition, the improvement in diastolic function was not relat ed to changes in SERCA and PLB gene expression, suggesting that enhanced my ocardial relaxation was related to the blockade of AII effects on myocyte f unction or through a reduction of ventricular hypertrophy itself or both.