Reverse remodeling of cardiac myocyte hypertrophy in hypertension and failure by targeting of the renin-angiotensin system

Background-ACE inhibitors (ACEIs) and angiotensin II type 1 (AT(1)) recepto r blockers are effective in reducing left ventricular mass in hypertension and heart failure. However, the ability of these drugs to reverse excessive myocyte lengthening and transverse growth in heart failure is unknown. Methods and Results-L-158,809 (an AT(1) blocker; AT(1)), enalapril (an ACEI ), and hydralazine (a vasodilator) were administered to spontaneously hyper tensive heart failure rats between 5 and 10 months of age (early treatment) and between 18 and 22 months of age (late treatment). After 4 months of tr eatment, hemodynamics and chamber dimensions were collected before left ven tricular myocyte isolation and subsequent analysis of myocyte shape. Each d rug reduced systolic blood pressures to normal values. In the early and lat e studies, the ACEI reduced myocyte volume. Myocyte length was also reduced in the late study. However, the AT(1) was most effective in reversing myoc yte dimensions to near-normal values in both studies. Hydralazine was ineff ective in reducing cell size but arrested progression of myocyte lengthenin g in the late study. Changes in myocyte shape reflected alterations in cham ber dimensions and wail thickness. Conclusions-Reversal of myocyte hypertrophy was produced in hypertensive/he art failure rats with an AT(1). The ACEI was effective but to a lesser exte nt. Results indicate that it is possible to significantly reverse myocyte r emodeling pharmacologically even if therapy is initiated near the onset of failure. Further work is needed to determine whether similar results can be obtained in humans.