Antihypertensive medications are the most efficient drugs in achieving regression of myocardial hypertrophy in both clinical studies and animal models of hypertension. Nevertheless, there is a lack of clear and concise comparative study of their effects on the modulation of cardiomyocyte morphology and function. Here, we assessed the tissue-protective actions of 2 of these drugs, the calcium channel blocker lacidipine (3 mg/kg/day) and the angiotensin-converting enzyme-inhibitor enalapril (10 mg/kg/day) in vivo, after 8 weeks of treatment of 12-week-old spontaneously hypertensive rats, as well as in vitro, after short-term (4 min) application to isolated cardiomyocytes. Left ventricular hypertrophy (LVH) was compared at organ, tissue, and single-cell level. Our data showed that both drugs prevented the LVH of 20-week-old spontaneously hypertensive rats, but only lacidipine significantly decreased the cardiomyocyte size. Similarly, the single-cell contractility was significantly lowered in lacidipine-treated rats only. The effect of lacidipine was initiated shortly after exposure to the drug in a dose-dependent manner at 0.5 Hz, as well as at 2 Hz, with EC(50) of 10(-7) mol/L. These results can help in understanding the effects of these drugs on the prevention of LVH.