Lambert M L, Callow I D, Feng Q P, Arnold J M
London Health Sciences Centre, Department of Pharmacology and Toxicology, University of Western Ontario, Canada.
Br J Clin Pharmacol. 1999 Jan;47(1):83-9. doi: 10.1046/j.1365-2125.1999.00852.x.
Neuropeptide Y (NPY) is a sympathetic neurotransmitter released with noradrenaline during sympathetic stimulation. Ageing has been shown to be associated with a reduction in alpha2 and beta-adrenoceptor mediated responses in veins, but it is not known whether NPY responsiveness is also altered with increasing age.
Using a dorsal hand vein technique, we examined NPY receptor responsiveness in 24 normal, healthy subjects (20-72 years; 10 males, 14 females). Graded infusions of NPY (25-2000 pmol min(-1)) were administered (5 min at each dose) into a dorsal hand vein. Venous distension at 45 mmHg was measured at 3-5 min of each infusion. Dose-response curves to NPY were constructed and the peak venoconstriction was calculated.
Dose-dependent venoconstriction was seen in all but one subject. The peak venoconstriction observed with NPY was significantly and negatively correlated with the age of the normal subjects (r=-0.63, P<0.01). When subjects were ranked from youngest to oldest and divided into tertiles, (20-40 years, n = 8; 41-55 years, n = 8; 56-72 years, n = 8), mean dose-response curves were different with the oldest tertile being significantly less responsive (P<0.05). The peak venoconstriction observed (% of control) was 65.1+/-7.0, 46.5+/-9.4, and 24.4+/-4.8%, respectively. The oldest tertile had a significantly decreased peak venoconstriction compared with the youngest tertile (P<0.01). Infusion of NPY into a dorsal hand vein had no systemic effects on heart rate or blood pressure in any of the subjects studied.
Hand vein responsiveness to exogenously infused NPY in normal subjects is decreased as age increases. The reduction of NPY-receptor-mediated responses with age may influence sympathetic nervous system control of the venous system with advancing age.
神经肽Y(NPY)是一种在交感神经刺激过程中与去甲肾上腺素一同释放的交感神经递质。衰老已被证明与静脉中α2和β肾上腺素能受体介导的反应减少有关,但尚不清楚NPY反应性是否也会随着年龄增长而改变。
采用手背静脉技术,我们检测了24名正常健康受试者(20 - 72岁;10名男性,14名女性)的NPY受体反应性。将NPY(25 - 2000 pmol min(-1))分级输注(每个剂量持续5分钟)到手背静脉中。在每次输注的3 - 5分钟时测量45 mmHg下的静脉扩张情况。构建NPY的剂量 - 反应曲线并计算最大静脉收缩。
除一名受试者外,所有受试者均出现剂量依赖性静脉收缩。NPY引起的最大静脉收缩与正常受试者的年龄呈显著负相关(r = -0.63,P < 0.01)。当受试者按年龄从小到大排序并分为三分位数时(20 - 40岁,n = 8;41 - 55岁,n = 8;56 - 72岁,n = 8),平均剂量 - 反应曲线不同,年龄最大的三分位数反应性明显较低(P < 0.05)。观察到的最大静脉收缩(对照的百分比)分别为65.1±7.0%、46.5±9.4%和24.4±4.8%。与最年轻的三分位数相比,年龄最大的三分位数最大静脉收缩明显降低(P < 0.01)。在所有研究的受试者中,将NPY输注到手背静脉对心率或血压均无全身影响。
正常受试者中,随着年龄增长,手背静脉对外源性输注NPY的反应性降低。随着年龄增长,NPY受体介导的反应减少可能会影响交感神经系统对静脉系统的控制。