The compliance of large elastic arteries in the cardiothoracic circulation declines with advancing age.1 This reduction contributes to the age-related increase in the incidence of cardiovascular disease. In particular, arterial compliance has been associated with a number of cardiovascular disorders prevalent in older adults, including isolated systolic hypertension, orthostatic and postprandial hypotension and left ventricular hypertrophy.2

Arterial compliance primarily is determined by the intrinsic elastic properties of the artery.3 The elements of the arterial wall that determine its compliance are the composition of elastin and collagen (structural determinants), and the vasoconstrictor tone exerted by its smooth muscle cells (functional determinant).4 Historically, the effects of human aging on central arterial compliance have focused on structural determinants. However, in doing so, the influence of increased sympathetic adrenergic tone on central arterial compliance has been largely overlooked. In this context, sympathetic nervous system activity increases markedly with advancing age in adult humans.5 Findings from our laboratory indicate that increased alpha-adrenergic stimulation and reduced nitric oxide bioavailability appear to be responsible, at least in part, for the age-associated augmentation in the vascular smooth muscle cell tone.6, 7 Thus, it is plausible to hypothesize that the age-related reduction in central arterial compliance is related to the elevation in sympathetic tone to the vasculature. In the present study, we tested this hypothesis by directly measuring arterial compliance and sympathetic nerve activity in groups of healthy young and older men.



We studied 16 young (20–35 years) and 17 older (55–70) healthy men. All subjects were nonobese, normotensive, nonsmoking, sedentary and nonmedicated. Older subjects were further evaluated for clinical evidence of cardiopulmonary disease with a physical examination and maximal exercise ECG. All participants gave their written informed consent before participating, and the Institutional Review Board examined and approved all procedures.


All measurements were performed following an abstinence of caffeine and a fast of 4 h. During the experimental sessions, each subject rested supine for 15 min in a quiet, temperature controlled room.

Arterial compliance was measured with the combination of ultrasound imaging of the right common carotid artery and simultaneous measurements of blood pressure via arterial applanation tonometry placed on the left common carotid artery as previously described by our laboratory.8 Common carotid artery diameter was measured from the images derived from an ultrasound machine (Toshiba SSH-140, Tochigi, Japan) equipped with a high-resolution linear-array transducer as previously described.8 A longitudinal image of the cephalic portion of the common carotid artery was acquired 1–2 cm proximal to the carotid bulb with the transducer placed at a 90 degree angle to the vessel so that near and far wall interfaces were clearly discernible. All image analyses were performed by the same investigator who was blinded to the group assignments or conditions of subjects.

Sympathetic nerve activity to the arterial vasculature in skeletal muscle (MSNA) was determined using peroneal microneurography.6 The neural activity was amplified, filtered, full-wave rectified and integrated (Nerve Traffic Analyzer, University of Iowa). Neurograms were considered acceptable as recordings of efferent MSNA according to previously published criteria.9

Statistical analyses

The Data are expressed as means±s.e.m. One-way ANOVA and ANCOVA were used to compare group means. Univariate regression and correlation analyses as well as partial correlation analyses were used to analyze the relation between variables of interest. A significance level of P<0.05 was set a priori to determine statistical significance.


Young and older subjects had similar BMI and systolic blood pressure (Table 1). Diastolic blood pressure was greater in older than in young subjects. Arterial compliance was lower and sympathetic nerve activity was higher in older compared with young men (both P<0.001). As shown in Figure 1, arterial compliance was inversely related to sympathetic nerve activity (r=−0.51; P<0.005). The correlation between arterial compliance and sympathetic nerve activity remained significant after adjusting for heart rate using partial correlational analyses (P<0.005). Carotid artery diameter was associated with MSNA (r=−0.493; P<0.005). Statistically correcting for sympathetic nerve activity using ANCOVA abolished the age-related difference in arterial compliance (P=0.35).

Table 1 Selected subject characteristics
Figure 1
figure 1

Relation between arterial compliance and muscle sympathetic nerve activity in healthy men varying widely in age.


Our results suggest that increases in the sympathetic tone of the arterial vasculature may have a mechanistic role in the reduction in compliance of large elastic arteries occurring with advancing age. These findings are consistent with, but considerably extend previous observations on this topic. Acute experimental increases in sympathetic-adrenergic tone decrease arterial compliance.10 Importantly, in the context of the present study, the sympathetic nervous system exerts a marked tonic restraint on the compliance of large arteries.11, 12 Our findings provide new insight into the state of primary adult human aging. Specifically, our results suggest that a key functional determinant (that is, sympathetic-adrenergic tone) may contribute importantly to the loss of central arterial compliance with age in humans.

We wish to emphasize that there are at least two experimental limitations associated with the present study. One is that it is not possible to measure sympathetic nerve activity to the carotid artery region in humans. As such, we determined sympathetic nerve activity directed to arterial blood vessels in leg skeletal muscle.13 However, the data from animal experiments indicate that cervical (neck) sympathetic nerve activities positively correlate with lumbar sympathetic nerve activities directed to the leg muscle vasculature.14 We should also emphasize that our findings regarding the relation between carotid artery compliance and sympathetic tone are based on the correlational data. Therefore, a cause-and-effect association between these events cannot be proven from the present results. For example, it is possible that the reduced arterial compliance in the carotid sinus area may lead to increased sympathetic nerve activity via diminished baroreflex restraint on the sympathetic outflow rather than the other way around.15

In conclusion, our findings are the first to show a significant and inverse relation between carotid artery compliance and sympathetic nerve activity in healthy men varying widely in age. As such, these observations provide the initial experimental support for the idea that increases in sympathetic-adrenergic smooth muscle tone may contribute significantly to the loss of compliance in the large elastic arteries with adult aging.