In hypertension, the blood pressure curve may be divided into two sets of components. The first set is mean arterial pressure, steady flow, and vascular resistance, thus acting on small arteries; the second set refers to large arteries, hence to pulse pressure, arterial stiffness, and wave reflections. The angiotensin-converting enzyme (ACE) inhibitor perindopril not only reduces mean arterial pressure but also acts specifically on pulse pressure. The effect on pulse pressure predominates on central rather than peripheral (brachial) large arteries, reducing aortic stiffness and most wave reflections. Such hemodynamic changes are not observed with standard β-blockade, which reduces aortic stiffness and brachial systolic and pulse pressure but not central pulse pressure and wave reflections. In hypertensive subjects, perindopril and other ACE inhibitors seem to predict more consistently the reduction of cardiovascular events, mainly of cardiac origin, than standard β-blockers alone. This effect is associated with the important biochemical finding that mechanotransductions of angiotensin and β-blockade are markedly different, acting in the former specifically on the α5β1 integrin complex and on the fibronectin ligand of arterial vessels.