Both aging and hypertension decrease the responsiveness of several receptor systems. The purpose of this study was to investigate the effect of aging versus hypertension on the blood pressure (BP), heart rate, and left ventricular (LV) responses to the alpha1-agonist phenylephrine in humans. Fourteen young (age, 21-40 years; range, 30+/-1 years; mean +/- SEM), and 18 older (age, 50-73 years; range, 60+/-1 years) healthy volunteers, as well as 10 young (age, 30-39 years; range, 36+/-1 years) and 15 older (age, 50- 64 years; range, 58+/-1 years) hypertensive subjects were studied. Phenylephrine was administered at four incremental rates for 8 min each. Cardiac responses were assessed by echocardiography. Phenylephrine caused twofold larger increases in systolic BP in young and older hypertensives and older normotensives, compared with young normotensives, but similar decreases in heart rate in all four groups. Younger normotensive subjects exhibited the largest decreases in stroke volume index, ejection fraction, and cardiac index in response to phenylephrine, despite similar increases in end-systolic stress for all groups. There is an age- and hypertension-related decrease in reflex vagal restraint in response to alpha1-adrenoceptor stimulation in humans, which leads to significant attenuation of the decrease in heart rate as well as in LV function in response to a pressor stimulus, and presumably therefore to enhanced systolic BP responses relative to young normotensive subjects.