We investigated whether cardiac apoptosis is stimulated in the heart of hypertensive patients and whether angiotensin II plays a role in such alteration. The study was performed in 28 patients with essential hypertension and no evidence of either ischemic cardiomyopathy or heart failure. After randomization, 14 patients were assigned to losartan and 14 patients to amlodipine treatment. At baseline and after 12 months, right septal endomyocardial biopsies were performed, and the number of apoptotic nuclei was assessed by DNA end-labeling (TUNEL). In addition, immunostaining for the active form of caspase-3 was also performed to assess apoptosis. Compared with normotensive autopsied hearts, both cardiomyocyte and noncardiomyocyte apoptosis were increased (P<0.001) in hypertensive hearts. Time-course changes in blood pressure during treatment were similar in the 2 groups of patients. In losartan-treated patients, both cardiomyocyte and noncardiomyocyte apoptosis decreased (P<0.05). Neither cardiomyocyte nor noncardiomyocyte apoptosis changed significantly in amlodipine-treated patients. These findings indicate that apoptosis is abnormally stimulated in the heart of patients with essential hypertension. Our data also suggest that the ability of antihypertensive treatment to inhibit cardiac apoptosis is independent of its antihypertensive efficacy. We propose that angiotensin II may participate in the stimulation of cardiac apoptosis in essential hypertension.