Sympathetic nervous system activity and alpha-adrenergic responsiveness inolder hypertensive humans

We have previously demonstrated in normotensive humans an age-associated in crease in sympathetic nervous system (SNS) activity combined with appropria te downregulation of alpha-adrenergic responsiveness. Impaired downregulati on of alpha-adrenergic responsiveness, despite a comparable level of SNS ac tivity, could contribute to higher blood pressure in older hypertensive hum ans. We measured arterial plasma norepinephrine (NE) levels and the extrava scular NE release rate (NE2) derived from [H-3]NE kinetics (to assess syste mic SNS activity), and platelet and forearm arterial adrenergic responsiven ess in 20 normotensive (N) and in 24 hypertensive (H), otherwise healthy, o lder subjects (60-75 yr). Although plasma NE levels were similar (N 357 +/- 27 vs. H 322 +/- 22 pg/ml; P = 0.37), NE2 tended to be greater in the hype rtensive group (H 2.23 +/- 0.21vs. N 1.64 +/- 0.20 mu g min(-1) m(-2); P = 0.11), and the NE metabolic clearance rate was greater (H 1,100 +/- 30 vs. N 900 +/- 50 ml/m(2); P = 0.004). In the hypertensive group, there was a gr eater a-agonist-mediated inhibition of platelet membrane adenylyl cyclase a ctivity and a NE- but not ANG II-mediated decrease in forearm blood flow. C ompared with normotensive subjects, in older hypertensive subjects I)NE met abolic clearance rate is increased, 2) systemic SNS activity tends to be in creased, and 3) arterial and platelet alpha-adrenergic responsiveness is en hanced. These results suggest that heightened SNS activity coupled with enh anced alpha-adrenergic responsiveness may contribute to elevated blood pres sure in older hypertensive humans.