The influence of aging on the human sympathetic nervous system and brain norepinephrine turnover

Abstract

The influence of aging on the human sympathetic nervous system and brain norepinephrine turnover. Am J Physiol Regulatory Integrative Comp Physiol 282: R909-R916, 2002; 10.1152/ ajpregu.00335.2001.-Investigating aging effects on the sympathetic nervous system and ascertaining underlying central nervous system (CNS) mechanisms mediating sympathetic stimulation is clinically pertinent because of the possible interconnection of cardiovascular disease development with age-dependent sympathetic nervous changes. Because of previous evidence linking human CNS neuronal noradrenergic function and sympathetic activity, we investigated the influence of aging on brain norepinephrine turnover in 22 healthy men aged 20-30 yr and 16 healthy men aged 60-75 yr by measuring the internal jugular venous overflow of norepinephrine and its lipophilic metabolites. Sympathoneural and adrenal medullary function was also studied, using plasma catecholamine isotope dilution methodology and regional central venous sampling. In the older men there was increased norepinephrine turnover in suprabulbar subcortical brain regions, 317 Ϯ 50 ng/min compared with 107 Ϯ 18 ng/min in younger men. A differentiated sympathetic nervous activation was also present in older men. Overall, levels of both cardiac and hepatomesenteric norepinephrine spillover were directly correlated with subcortical norepinephrine turnover. These findings suggest that in sympathetic nervous activation accompanying aging, as has previously been demonstrated with the sympathetic nervous stimulation in human hypertension and heart failure, there is an underlying sympathoexcitatory influence of noradrenergic projections to suprabulbar subcortical regions. epinephrine; heart; kidneys; adrenal medulla THE FUNCTION OF THE HUMAN sympathetic nervous system is altered in important ways by aging. These changes involve both the properties of the adrenergic receptors and the outflow of sympathetic neural traffic to individual organs (32). Based in large part on subcutaneous multiunit microneurographic recording from sympathetic fibers distributed in the company of motor nerves (1, 28, 37) and on the measurement of the spillover of the sympathetic neurotransmitter norepinephrine to plasma (14,15,36), there is now unequivocal evidence that progressive sympathetic activation occurs with aging. This sympathetic stimulation appears to involve the sympathetic outflow to the heart, the skeletal muscle vasculature, and the gut and liver, but to exclude the kidneys (14, 15). The nature of the underlying disturbance in central nervous system (CNS) sympathetic control, however, remains unknown.The impetus for seeking to better understand the central nervous mechanisms by which aging causes sympathetic activation has come in part from recognition that in a variety of cardiovascular disorders, including cardiac failure, essential hypertension, and ventricular arrhythmias, for all of which incidence rises with age, the sympathetic nervous system is causally involved (11). Antiadrenergic drugs have co...

Effects of life-long caloric restriction and voluntary exercise on age-related changes in levels of catecholamine biosynthetic enzymes and angiotensin II receptors in the rat adrenal medulla and hypothalamus

“…In particular, the elderly do not regulate blood pressure as well as young people, and age-related increases in the prevalence of hypertension are associated with elevated morbidity and mortality (National High Blood Pressure Education Program Working Group 1994;Tuck, 1989). The elevation in blood pressure with age is attributable, at least in part, to an increase in sympathetic nervous activity (Esler M. et al, 2002;Esler M.D. et al, 1995;Seals and Dinenno, 2004), and sustained elevation of catecholaminergic activity requires increased levels of catecholamine biosynthesizing enzymes in the adrenal medulla and peripheral sympathetic ganglia.…”

Sympathetic nervous system behavior in human obesity

“…Chronic activation of supra-bulbar subcortical noradrenergic neurons has been suggested to contribute to peripheral SNS activation in heart failure (Lambert et al, 1995), essential hypertension (Ferrier et al, 1992), and aging (Esler et al, 2002). Thus, it is possible that this may also be a potential mechanism contributing to SNS activation in obesity.…”

Influences of Norepinephrine Transporter Function on the Distribution of Sympathetic Activity in Humans

“…Several single nucleotide polymorphisms in the NET gene are associated with substantial alterations in NET function. 28 Moreover, abnormalities in the distribution of sympathetic activity between the heart, vasculature, and kidney have been described with aging, 29 as in different pathophysiological conditions, such as heart failure, 30 POTS, 20 and obesity. 31 NET abnormalities may possibly be important in this regard.…”