In spontaneously hypertensive rats (SHRs) we evaluated the effects of 35 and 70 days of treatment with nisoldipine (2 mg/g of food) vs. minoxidil (120 mg/L of drinking water) on cardiac anatomy [i.e., left ventricular (LV) and right ventricular (RV) weights and LV internal diameter and wall thickness] and cardiac sympathetic activity assessed by the norepinephrine turnover rate. The minoxidil-induced antihypertensive response was associated with a marked increase in cardiac sympathetic activity, potentiation of RV hypertrophy (RVH), and the development of eccentric LV hypertrophy (LVH). Nisoldipine decreased both blood pressure (BP) and cardiac sympathetic activity, but caused only small decreases in LV weight and LV wall thickness and no change in RV weight. With regard to minoxidil, the increase in sympathetic activity may contribute to the minoxidil-induced potentiation of cardiac mass. Nisoldipine, despite decreasing BP as well as cardiac sympathetic activity, unexpectedly resulted in only a small decrease in cardiac mass, suggesting that additional mechanisms may play a role in the effects of calcium antagonists on cardiac mass.