Numerous prospective studies have shown that high heart rate is related to the development of hypertension, atherosclerosis, and incidence of cardiovascular events. Experimental studies in monkeys have shown that high heart rate has direct atherogenic effects on the arteries as a result of increased wall stress. However, clustering of several risk factors for coronary artery disease in persons with high heart rate suggests that sympathetic overactivity also accounts for part of the increased cardiovascular morbidity that is observed in persons with tachycardia. Indeed, experimental studies have shown that heightened sympathetic tone can cause obesity, hyperinsulinemia, and insulin resistance, which in the long term can promote the development of atherosclerosis. Through its interaction with plasma insulin, sympathetic overactivity can promote the development of left ventricular hypertrophy. Sympathetic activation can also increase hematocrit and precipitate a procoagulant state. Angiotensin II has an effect both on the central nervous system, enhancing sympathetic outflow, and on the peripheral sympathetic nerves. Among the angiotensin II receptor antagonists, eprosartan showed a particular ability to block presynaptic angiotensin II receptor 1 (AT(1)) receptors at neuro-effector junctions in the sympathetic nervous system, as well as AT(1) receptors in blood vessels. This dual action may represent an important advance in treatment of elevated blood pressure.