In rats, an increase in heart rate by pacing is accompanied by progressive large-artery stiffening. Whether this is also the case in humans is unknown. We enrolled 20 patients who were chronically implanted with a pacemaker because of atrioventricular block or sick sinus syndrome. Arterial distensibility was measured by an echo-tracking device. In 10 patients, the evaluation was performed on the radial artery by using continuous finger blood pressure measurements, whereas in the remaining 10 patients, the common carotid artery was studied with a semiautomatic measure of brachial artery blood pressure. Diastolic diameter, systodiastolic diameter change, and distensibility were obtained at baseline (heart rate 63+/-2 beats/min) and after atrial and ventricular sequential pacing at a heart rate of 90 and 110 beats/min. At baseline, the diameter was 7.8+/-0.3 mm in the carotid artery and 2.4+/-0.1 mm in the radial artery; the respective systodiastolic diameter change values were 375.4+/-31.0 and 55.9+/-9.0 (microm) and the distensibility values were 1.4+/-0.1 and 0.7+/-0.1 (1/mm Hg 10-3). Blood pressure and diameter were not significantly modified by increasing heart rate, which markedly modified systodiastolic diameter change and distensibility. In the radial artery, distensibility was reduced by 47% (P<0.05) at a heart rate of 90 beats/min with no further reduction at 110 beats/min. In the carotid artery, distensibility was reduced by 20% at a heart rate of 90 beats/min (P<0.05) with a further reduction at 110 beats/min (45%, P<0.05). These data provide the first evidence in humans that acute increases in heart rate markedly affect arterial distensibility and that this occurs in both large- and middle-size muscle arteries within the range of "normal" heart rate values.