Sympathetic nervous system activity and α-adrenergic responsiveness in older hypertensive humans

We have previously demonstrated in normotensive humans an age-associated increase in sympathetic nervous system (SNS) activity combined with appropriate downregulation of α-adrenergic responsiveness. Impaired downregulation of α-adrenergic responsiveness, despite a comparable level of SNS activity, could contribute to higher blood pressure in older hypertensive humans. We measured arterial plasma norepinephrine (NE) levels and the extravascular NE release rate (NE ) derived from [ H]NE kinetics (to assess systemic SNS activity), and platelet and forearm arterial adrenergic responsiveness in 20 normotensive (N) and in 24 hypertensive (H), otherwise healthy, older subjects (60-75 yr). Although plasma NE levels were similar (N 357 ± 27 vs. H 322 ± 22 pg/ml; P = 0.37), NE tended to be greater in the hypertensive group (H 2.23 ± 0.21 vs. N 1.64 ± 0.20 μg ⋅ min ⋅ m ; P = 0.11), and the NE metabolic clearance rate was greater (H 1,100 ± 30 vs. N 900 ± 50 ml/m ; P = 0.004). In the hypertensive group, there was a greater α-agonist-mediated inhibition of platelet membrane adenylyl cyclase activity and a NE- but not ANG II-mediated decrease in forearm blood flow. Compared with normotensive subjects, in older hypertensive subjects 1) NE metabolic clearance rate is increased, 2) systemic SNS activity tends to be increased, and 3) arterial and platelet α-adrenergic responsiveness is enhanced. These results suggest that heightened SNS activity coupled with enhanced α-adrenergic responsiveness may contribute to elevated blood pressure in older hypertensive humans.