The effects of age on human venous responsiveness to neuropeptide Y

Abstract

Aims: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Figure 1

Sample original tracing of dorsal hand vein distension during intravenous administration of NPY in a 20 year old normal subject.

Figure 2

Average superficial hand vein response to graded infusions of NPY in all subjects (n = 24). Results are given as means±s.e. mean.

Figure 3

Average superficial vein response to graded infusions of NPY in younger (□, n = 8), middle (○, n = 8), and older (▵, n = 8) subjects. Results are given as means±s.e. mean. * Significantly different from younger and middle-aged subjects (P<0.05).

Figure 4

Correlation between peak venoconstriction to NPY and age in all subjects, r = −0.63, P<0.01. (female closed symbols, male open symbols). ▪, □ young, n = 8 •, ○ middle, n = 8 and ▴, ▵ older, n = 8 subjects. r = −0.56, P<0.01. Note: Two older subjects excluded due to non-detectable plasma NPY levels in the blood sample.

Figure 5

Correlation between peak venoconstriction to NPY and plasma NPY levels in all subjects (female closed symbols, male open symbols). ▪, □ young, n = 8 •, ○ middle, n = 8 and ▴, ▵ older, n = 8 subjects. r = −0.56, P<0.01. Note: Two older subjects excluded due to non-detectable plasma NPY levels in the blood sample.

Figure 6

Correlation between plasma noradrenaline and plasma NPY in all subjects. (female closed symbols, male open symbols). ▪, □ young, n = 8, •, ○ middle, n = 8 and ▴, ▵ older, n = 8 subjects. r = 0.59, P<0.01. Note: Two young subjects excluded due to laboratory contamination of supplied blood sample for plasma NA levels. Two older subjects (same as in Figure 5) excluded for non-detectable plasma NPY levels.