Raskind M A, Peskind E R, Veith R C, Beard J C, Gumbrecht G, Halter J B
Geriatric Research, Education and Clinical Center, Seattle, Veterans Administration, Medical Center, Washington 98108.
J Clin Endocrinol Metab. 1988 Feb;66(2):438-43. doi: 10.1210/jcem-66-2-438.
To evaluate the effect of advanced age on central nervous system noradrenergic activity, cerebrospinal fluid (CSF) and plasma norepinephrine (NE) concentrations were measured concurrently in 14 older [mean, 65 +/- 9 (+/- SD) yr] and 33 younger (25 +/- 2 yr) normal men. CSF NE was significantly higher in older men than in young men [214 +/- 75 (+/- SD) vs. 164 +/- 56 pg/mL (1.26 +/- 0.44 vs. 0.97 +/- 0.33 nmol/L); P less than 0.02] as was plasma NE [282 +/- 103 vs. 211 +/- 63 pg/mL (1.67 +/- 0.61 vs. 1.25 +/- 0.37 nmol/L); P less than 0.02]. Subgroups of young and older men underwent two lumbar punctures, one of which was performed 100 min after the administration of 5 micrograms/kg oral clonidine. The young (n = 7) and older (n = 7) men had similar plasma clonidine levels [1.0 +/- 0.1 vs. 0.8 +/- 0.1 ng/mL (4.35 +/- 0.43 vs. 3.48 +/- 0.78 nmol/L)] and CSF clonidine levels [0.18 +/- 0.02 vs. 0.22 +/- 0.03 ng/mL (0.78 +/- 0.09 vs. 0.96 +/- 0.13 nmol/L)]. The suppression of CSF NE by clonidine was significantly greater (P less than 0.015) in young men [189 +/- 44 to 104 +/- 26 pg/mL (1.12 +/- 0.26 to 0.62 +/- 0.15 nmol/L)] than in older men [190 +/- 49 to 164 +/- 58 pg/mL (1.12 +/- 0.29 to 0.97 +/- 0.34 nmol/L)]. In contrast, the suppression of plasma NE by clonidine did not significantly differ between young [242 +/- 72 to 93 +/- 24 pg/mL (1.43 +/- 0.43 to 0.55 +/- 0.14)] and older men [285 +/- 102 to 167 +/- 84 pg/mL (1.68 +/- 0.60 to 0.99 +/- 0.50 nmol/L)]. These data suggest that decreased sensitivity of alpha 2-adrenergic mechanisms regulating CNS noradrenergic activity may contribute to increased CNS noradrenergic activity with aging.
为评估高龄对中枢神经系统去甲肾上腺素能活性的影响，我们同时测定了14名老年男性（平均年龄65±9岁，±标准差）和33名年轻男性（25±2岁）正常男性的脑脊液（CSF）和血浆去甲肾上腺素（NE）浓度。老年男性的脑脊液NE水平显著高于年轻男性[214±75（±标准差）对164±56 pg/mL（1.26±0.44对0.97±0.33 nmol/L）；P<0.02]，血浆NE水平也是如此[282±103对211±63 pg/mL（1.67±0.61对1.25±0.37 nmol/L）；P<0.02]。年轻和老年男性亚组均接受了两次腰椎穿刺，其中一次在口服5微克/千克可乐定100分钟后进行。年轻男性（n = 7）和老年男性（n = 7）的血浆可乐定水平相似[1.0±0.1对0.8±0.1 ng/mL（4.35±0.43对3.48±0.78 nmol/L）]，脑脊液可乐定水平也相似[0.18±0.02对0.22±0.03 ng/mL（0.78±0.09对0.96±0.13 nmol/L）]。可乐定对脑脊液NE的抑制作用在年轻男性中[189±44至104±26 pg/mL（1.12±0.26至0.62±0.15 nmol/L）]显著大于老年男性[190±49至164±58 pg/mL（1.12±0.29至0.97±0.34 nmol/L）]（P<0.015）。相比之下，可乐定对血浆NE的抑制作用在年轻男性[242±72至93±24 pg/mL（1.43±0.43至0.55±0.14）]和老年男性[285±102至167±84 pg/mL（1.68±0.60至0.99±0.50 nmol/L）]之间没有显著差异。这些数据表明，调节中枢神经系统去甲肾上腺素能活性的α2-肾上腺素能机制敏感性降低可能是导致衰老过程中中枢神经系统去甲肾上腺素能活性增加的原因。
