DIE ROLLE DES KARDIALEN ANGIOTENSIN-KONVERSIONSENZYMS BEI DER EXPERIMENTELLEN MYOKARDHYPERTROPHIE DER RATTE

Cardiac growth in response to pressure overload may be modified by neurohumoral activation. To study the contribution of the renin angiotensin system (RAS) to cardiac hypertrophy (LVH), rats were treated with either vehicle (VEH, n = 11), hydralazine (HYD, 20 mg/kg/d, n = 16), ramipril (RAM, 10 mg/kg/d, n = 14), or losartan (LOS, 40 mg/kg/d, n = 13) during weeks 6-12 after banding of the ascending aorta. VEH and HYD rats were characterized by a 1.66 and 1.88-fold increase of left ventricular to body weight ratios (LV/BW), respectively. In parallel, cardiac ACE activities were increased (p < 0.05, each vs sham operated controls, n = 16) and closely correlated to LV/BW (r = 0.8, p < 0.001) and RV/BW (r = 0.8, p < 0.001). In contrast, plasma renin or ACE activities were neither elevated nor correlated to severity of LVH. Blockade of the RAS by RAM or LOS resulted in a blunted increase of LV/BW (1.3-fold, p < 0.05, each vs sham); thus, resulting in lower LV/BW than in VEH and HYD groups (p < 0.05, each). The attenuation of LVH by RAM or LOS was not explained by blood pressure reduction that was similar in the HYD group. In summary, in this model cardiac ACE - but not plasma renin - is closely correlated to the degree of LVH. Furthermore, ACE or angiotensin II-type1 receptor blockade may promote regression of pressure overload LVH by mechanisms that are, in part, independent of hemodynamic drug effects.