Studies on spontaneously hypertensive rats (SHR), which represent a model of genetically determined arterial hypertension, revealed that cardiac hypertrophy can be controlled by blood pressure normalization by use of various antihypertensive drugs such as hydralazine, captopril, metoprolol, guanethidine, and alpha-methyldopa. Adrenergic influences seem to play a part except for left ventricular (LV) systolic unloading on cardiac hypertrophy, because LV hypertrophy was quantitatively less expressed after a combined therapy with both metoprolol and hydralazine than after a single hydralazine treatment, although blood pressure was not different between the groups. To study whether nifedipine can cause an already existing cardiac hypertrophy to regress, 20-week-old SHR were treated with nifedipine for a period of 20 weeks. After nifedipine treatment, LV muscle mass/body weight ratio was significantly less than before therapy (2.13 +/- 0.18 vs. 2.37 +/- 0.30 mg/g; p less than 0.05). Mass to volume ratio, i.e., quotient of LV muscle mass and LV end-diastolic volume, dropped from 3.40 +/- 0.66 to 3.07 +/- 0.30 mg/microliters (p less than 0.05) after therapy. Accordingly, an antihypertensive treatment with the calcium channel blocker nifedipine can cause an already existing LV hypertrophy in SHR to regress. Because blood pressure reduction resulting from therapy with beta-receptor-blockers, vasodilators, sympatholytic drugs, angiotensin converting enzyme inhibitors, and calcium channel blockers has qualitatively similar effects with respect to causing regression of hypertrophy, reversal of cardiac hypertrophy seems to be mainly related to the reduced LV systolic load. Specific pharmacodynamic effects may only modulate the extent of LV mass reduction along with blood pressure normalization.