Rise in Plasma Noradrenaline with Age Results from an Increase in Spillover Rate

MacGilchrist, Alastair; Hawksby, C.; Howes, L. G.; Reid, John L.

doi:10.1159/000212994

Cited by 22 publications

(7 citation statements)

References 15 publications

(24 reference statements)

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“…The earlier investigations had established that net whole body SNS activity, as estimated from total plasma norepinephrine spillover, was greater in older healthy adults compared with young controls (31,43,56,70). As summarized in a previous review (59), we extended these observations by demonstrating that this increase in net systemic SNS activity with advancing age is the result of increases in SNS outflow to several peripheral tissues, including the heart, the liver-gut circulation, and skeletal muscle.…”

supporting

confidence: 64%

“…For more than a decade we have been investigating the effects of primary human aging (i.e., aging in the absence of chronic clinical disease) on the SNS and its regulation of cardiovascular and metabolic function. This work has focused on three main areas of interest.Our initial efforts (11, 12, 23-25, 48 -50, 65, 66) sought to build on earlier studies (3,27,31,43,52,56,62,70,77,78) aimed at determining the effects of aging on SNS behavior under tonic (resting) conditions and in response to acute physical and mental-emotional stress. The earlier investigations had established that net whole body SNS activity, as estimated from total plasma norepinephrine spillover, was greater in older healthy adults compared with young controls (31,43,56,70).…”

mentioning

confidence: 99%

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Collateral damage: cardiovascular consequences of chronic sympathetic activation with human aging

Seals

Dinenno²

2004

American Journal of Physiology-Heart and Circulatory Physiology

119

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Adult aging in humans is associated with marked and sustained increases in sympathetic nervous system (SNS) activity to several peripheral tissues, including the heart, the gut-liver circulation, and skeletal muscle. This chronic activation of the peripheral SNS likely is, at least in part, a primary response of the central nervous system to stimulate thermogenesis to prevent further fat storage in the face of increasing adiposity with aging. However, as has been proposed in obesity hypertension, this tonic activation of the peripheral SNS has a number of adverse secondary cardiovascular consequences. These include chronic reductions in leg blood flow and vascular conductance, increased tonic support of arterial blood pressure, reduced limb and systemic alpha-adrenergic vasoconstrictor responsiveness, impaired baroreflex buffering, large conduit artery hypertrophy, and decreased vascular and cardiac responsiveness to beta-adrenergic stimulation. These effects of chronic age-associated SNS activation on the structure and function of the cardiovascular system, in turn, may have important implications for the maintenance of physiological function and homeostasis, as well as the risk of developing clinical cardiovascular and metabolic diseases in middle-aged and older adults.

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supporting

confidence: 64%

mentioning

confidence: 99%

Collateral damage: cardiovascular consequences of chronic sympathetic activation with human aging

Seals

Dinenno²

2004

American Journal of Physiology-Heart and Circulatory Physiology

119

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“…Norepinephrine (NE) NE release increases with aging. [20][21][22][23][24][25] NE increased with aging (Figures 2 and 6). Increased NE pl in younger subjects with lower GSH (Figure 4).…”

Section: 2mentioning

confidence: 89%

“…24 However, one study did find increased resting NE release with aging. 25 NE spillover from the synapse into plasma is selectively enhanced with aging in several vascular beds, including those of the heart 20,21,24,26 and hepatomesenteric area. 20,23 In the heart, this is at least partially due to reduced intrasynaptic reuptake of NE, 24,27 suggesting that the sympathetic drive is chronically increased in the aging heart.…”

Section: Introductionmentioning

confidence: 99%

Contributions of the sympathetic nervous system, glutathione, body mass and gender to blood pressure increase with normal aging: influence of heredity

Kennedy

Rao

Botiglieri³

et al. 2005

J Hum Hypertens

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Body mass and sympathetic activity increase with aging and might underlie blood pressure (BP) elevation. Increased body mass index (BMI) may elevate BP by increasing sympathetic activity. Glutathione (GSH) can decrease BP, and declines with aging. We measured systolic (SBP) and diastolic BP, BMI, plasma (NE pl ) and urine norepinephrine (NE u ), and plasma GSH in n ¼ 204 twins across the age spectrum. BP correlated directly with BMI, NE pl , and NE u , but inversely with GSH. Age correlated with BP, BMI, NE pl , and NE u . BP, BMI, NE pl , and NE u were higher in older subjects than younger subjects, whereas GSH was lower with aging. In older subjects with high (above median) NE pl , SBP was 8 mmHg higher than in those of comparable age with low NE. In younger subjects with high GSH, BP was significantly lower than in younger subjects having low GSH. NE u was significantly reduced in young high-BMI subjects vs young low-BMI subjects. The heritability (h 2 ) of NE pl, NE u , and GSH ranged from B50 to B70%, and these biochemical quantities were considerably more heritable than BP. We conclude that increases in sympathetic activity contribute to aging-induced SBP elevations, especially in older females. GSH reductions apparently participate in aging-induced BP elevations, most strongly in males. BMI increases contribute to BP elevations, particularly in younger subjects. BMI elevations apparently raise BP mainly by peripheral mechanisms, with generally little sympathetic activation. Substantial h 2 for plasma GSH, NE, and urine NE suggests that such traits may be useful 'intermediate phenotypes' in the search for genetic determinants of BP.

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“…With advancing age, there is a general consensus that tonic basal sympathetic activity and stimulus-induced activation of the SNS in men progressively increases. This increase in basal SNS activity is reflected by a progressive rise in basal circulating norepinephrine (NE) [5][6][7] , mean arterial blood pressure [8][9][10] and stress-induced SNS activation [11][12][13][14] . The age-related rise in basal sympathetic tone in men emerges in middle age [15][16][17] and is target organ specific, occurring in the heart, the liver-gut circulation and skeletal muscle [18][19][20][21] , but not in the adrenal medulla and kidney [22,23] .…”

Section: Introductionmentioning

confidence: 99%

Sympathetic Nervous System and Lymphocyte Proliferation in the Fischer 344 Rat Spleen: A Longitudinal Study

Bellinger¹,

Silva²,

Millar³

et al. 2008

Neuroimmunomodulation

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Aging is associated with reduced cellular immunity, which leads to increased rates of infectious disease, cancer and autoimmunity in the elderly. Previous findings from our laboratory revealed an age-related decline in sympathetic innervation of immune organs that affects immunity. These studies suggested potential sympathetic nervous system involvement in age-induced immune dysregulation. Objectives: The purpose of this study was to longitudinally characterize the effects of age on sympathetic neurotransmission in the spleen and net sympathetic activity/tone in male Fischer 344 rats. Methods: Splenic sympathetic neurotransmission was evaluated between 8 and 24 months of age by (1) splenic norepinephrine (NE) concentration and turnover, (2) β-adrenergic receptor (β-AR) expression and (3) β-AR-stimulated splenocyte cAMP production. Measures of sympathetic neurotransmission were correlated with age-related changes in Concanavalin A (Con A)-stimulated splenocyte proliferation. Results: Splenic NE turnover increased during middle age, then subsequently declined by 18 months of age compared with 8-month-old controls (young). Splenic NE concentration increased at 10 months and decreased at 18–24 months, compared with young rats; however, plasma NE levels were not affected by age. Plasma epinephrine levels were decreased at 24 months. NE synthesis blockade increased and decreased the rate of plasma catecholamine depletion in middle and old age, respectively. β-AR-stimulated cAMP production increased in splenocytes by 15 months. An age-related decrease in Con A-induced splenocyte proliferation was apparent by 10 months and persisted through 24 months. The decline in Con A-induced splenocyte proliferation correlated with the age-related increase in cAMP production. Conclusions: Aging alters sympathetic nervous system metabolism in the spleen to affect β-AR signaling to splenocytes, suggesting that altered sympathetic-immune modulation changes are evident by early middle age.

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Rise in Plasma Noradrenaline with Age Results from an Increase in Spillover Rate

Cited by 22 publications

References 15 publications

Collateral damage: cardiovascular consequences of chronic sympathetic activation with human aging

Collateral damage: cardiovascular consequences of chronic sympathetic activation with human aging

Contributions of the sympathetic nervous system, glutathione, body mass and gender to blood pressure increase with normal aging: influence of heredity

Sympathetic Nervous System and Lymphocyte Proliferation in the Fischer 344 Rat Spleen: A Longitudinal Study

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