Journal of Applied Physiology Track the topics, authors and articles important to you
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 82: 1869-1874, 1997;
8750-7587/97 $5.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mazzeo, R. S.
Right arrow Articles by Esler, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mazzeo, R. S.
Right arrow Articles by Esler, M.

Journal of Applied Physiology
Vol. 82, No. 6, pp. 1869-1874, June 1997
EXERCISE AND MUSCLE

Norepinephrine spillover at rest and during submaximal exercise in young and old subjects

Robert S. Mazzeo1, Chakravarthi Rajkumar2, Garry Jennings2, and Murray Esler2

1 Department of Kinesiology, University of Colorado, Boulder, Colorado 80309; and 2 Baker Medical Research Institute, Prahran 3181, Victoria, Australia

ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES

ABSTRACT

Mazzeo, Robert S., Chakravarthi Rajkumar, Garry Jennings, and Murray Esler. Norepinephrine spillover at rest and during submaximal exercise in young and old subjects. J. Appl. Physiol. 82(6): 1869-1874, 1997.---Aging is associated with elevations in plasma norepinephrine concentrations. The purpose of this investigation was to examine total body and regional norepinephrine spillover as an indicator of sympathetic nerve activity. Eight young (26 ± 3 yr) and seven old (69 ± 5 yr) male subjects were studied at rest and during 20 min of submaximal cycling exercise at 50% of peak work capacity. Norepinephrine spillover was determined by continuous intravenous infusion of [3H]norepinephrine. Arterial norepinephrine concentrations were significantly greater at rest for old vs. young subjects (280 ± 36 vs. 196 ± 27 ng/ml, respectively). Whereas total norepinephrine spillover did not differ between groups at rest, hepatomesenteric norepinephrine spillover was 50% greater in old subjects compared with their young counterparts (51 ± 7 vs. 34 ± 5 ng/min, respectively). Additionally, norepinephrine clearance rates at rest were significantly lower for the old subjects (-23%). During exercise, plasma norepinephrine concentrations increased compared with rest, with old subjects again demonstrating greater values than the young group. Hepatomesenteric norepinephrine spillover was significantly greater (+36%) during exercise for old subjects compared with young; however, no difference was found for whole body spillover rates between age groups. Norepinephrine clearance rates remained depressed (-30%) in the old subjects during exercise. Clearance of epinephrine mirrored that for norepinephrine both at rest and during exercise across age groups. It was concluded that in old subjects, a reduction in norepinephrine clearance and an increase in regional norepinephrine spillover can account for the higher plasma norepinephrine concentrations observed at rest. This relationship is not exacerbated by the stress imposed during an acute bout of exercise.

sympathetic nerve activity; epinephrine; hepatomesenteric; aging

INTRODUCTION

ELEVATED RESTING CONCENTRATIONS of plasma norepinephrine have been associated with advancing age in humans (5, 6, 8, 19). Norepinephrine in plasma is mainly derived from sympathetic nerves, representing the transmitter escaping neuronal uptake and local metabolism and spilling over into the circulation. As a result, increased plasma norepinephrine concentrations observed with aging are generally assumed to reflect increases in sympathetic nerve activity. Measurements of norepinephrine spillover, which is a reliable marker of sympathetic nerve firing rates, suggest that an increase in sympathetic nerve activity does account, in part, for the increased plasma norepinephrine concentrations associated with age. However, this increase in sympathetic nerve activity does not appear to be global because certain tissues such as the kidney and adrenal medulla do not demonstrate any age-related increases in activity, whereas the heart and skeletal muscle do indicate increased activity (4, 6, 9, 14, 19). Furthermore, it is also possible that the greater tissue norepinephrine release into the circulation with age is not related to increases in sympathetic nerve activity but rather to diminished capacity for norepinephrine reuptake (6, 8).

Age-related decreases in the ability for plasma norepinephrine removal and clearance may also contribute to the increase in plasma norepinephrine concentration found with age. Reductions in norepinephrine reuptake ability, diminished beta -adrenergic responsiveness, or lower organ blood flow could contribute to a decrease in norepinephrine clearance, yielding higher plasma concentrations (1, 6, 8, 13, 17).

In response to stressful stimuli (e.g., physical exercise, hypoglycemia, upright posture), the rise in plasma norepinephrine concentrations is generally found to be greater in old compared with young individuals (7, 11, 20, 21). It has been suggested that this exaggerated plasma norepinephrine increase results from enhanced sympathetic nerve activity and transmitter release in an attempt to compensate for reduced target organ responsiveness to adrenergic stimulation (7, 10, 12). However, faulty norepinephrine uptake or reduced plasma clearance may also be responsible. Thus it was the purpose of this study to examine total body norepinephrine spillover, regional specific spillover, and plasma catecholamine clearance rates in young and old subjects both at rest and during the stress of 20 min of submaximal exercise.

MATERIALS AND METHODS

Experimental subjects. Subjects consisted of eight young (26 ± 3 yr) and seven old (69 ± 5 yr) male volunteers. All subjects underwent initial medical screening, including a medical history, clinical examination, and standard blood analyses. Subjects were relatively sedentary but otherwise healthy individuals not currently on any medication. Individuals were admitted into the study if they demonstrated no clinical signs or symptoms of heart disease and hypertension and had a normal electrocardiogram (ECG) in response to an exercise stress test. All subjects read and signed an informed consent approved by the Ethics Review Committee of the Alfred Hospital before experimentation.

General procedures. All experiments involving norepinephrine tracer techniques were performed in the morning after an overnight fast. Once in the laboratory, subjects were given a standard light breakfast (no caffeine) to minimize the chance of vasovagal syncope during the catheterization procedure. A 21-gauge cannula was inserted percutaneously into a radial artery while the subject was under local anesthesia. A central venous catheter was introduced via an antecubital venous sheath and positioned fluoroscopically into the left hepatic vein. Tritiated norepinephrine was continuously infused for determination of plasma norepinephrine kinetics via a dorsal vein catheter.

Exercise procedures. All subjects initially participated in a graded exercise test to exhaustion by supine electrically braked bicycling. Subjects cycled at 60 revolutions/min at an initial workload of 25 W. The workload was increased 15 W every 2 min until subjects could no longer maintain pedaling frequency, defined here as peak work capacity. Peak work capacity determined from this exercise test was 253 ± 24 and 122 ± 10 W for young and old subjects, respectively. Maximal heart rates observed were 184 ± 4 and 143 ± 3 beats/min for young and old subjects, respectively.

One week after the graded exercise test, subjects returned to the laboratory for the norepinephrine tracer experiments. After insertion of catheters, subjects rested quietly for ~60 min. Subjects then exercised on the same bicycle ergometer at 50% of peak work capacity for 20 min (136 ± 9 and 60 ± 6 W for young and old subjects, respectively). Blood was sampled from the central venous and arterial catheter before exercise and at 5, 10, and 20 min during exercise for catecholamine and tracer determinations. Heart rate was continuously monitored via a modified V5 ECG lead.

Norepinephrine kinetics. Measurements of total and hepatomesenteric norepinephrine spillover to plasma were made by continuous intravenous infusion of tritiated norepinephrine (0.70 µCi/min levo-[7-3H]norepinephrine, New England Nuclear, Boston, MA; specific activity 14-20 Ci/mmol). Tritiated norepinephrine is infused for 60 min to establish steady-state plasma concentration before sampling (5).

Measurement of spillover to the plasma of norepinephrine from the hepatomesenteric and the body as a whole is used to estimate the liver and overall sympathetic activity (integrated nerve firing rate). The relationship that exists between the rate of sympathetic nerve firing in an organ and the overflow of norepinephrine into its venous drainage provides the experimental justification for the use of transmitter spillover measurements in the study of sympathetic nervous function (2, 5, 6).

At steady state, during peripheral intravenous infusion of a tracer dose of tritiated norepinephrine, the total norepinephrine spillover to plasma and total plasma norepinephrine clearance can be calculated as follows
total norepinephrine spillover 
= <FR><NU>[<SUP>3</SUP>H]NE infusion rate (dpm/min)</NU><DE>plasma NE specific activity (dpm/pg)</DE></FR>
total norepinephrine clearance 
= <FR><NU>[<SUP>3</SUP>H]NE infusion rate (dpm/min)</NU><DE>plasma [<SUP>3</SUP>H]NE concentration (dpm/ml)</DE></FR>
where dpm is disintegrations per minute of tritiated norepinephrine ([3H]NE).

The rate of norepinephrine spillover from the hepatomesenteric circulation is calculated according to the Fick principle with adjustment for norepinephrine uptake across the organs, by using the fractional extraction of titrated norepinephrine
organ norepinephrine spillover 
= [(NE<SUB>v</SUB> − NE<SUB>a</SUB>) + (NE<SUB>a</SUB> × NE<SUB>ex</SUB>)] × OPF
where NEv is plasma norepinephrine concentration in the hepatic vein, NEa is arterial plasma norepinephrine concentration, NEex is the fractional extraction of tritiated norepinephrine in a single passage through the hepatic bed, and OPF is organ plasma flow (hepatomesenteric; ml/min). Hepatic plasma flow was derived from measurements of the steady-state total body clearance and hepatic extraction of indocyanine green (2).

Catecholamine analysis. An aliquot of blood for catecholamine determination was collected into ice-chilled tubes containing ethylene glycol-bis(beta -aminoethyl ether)-N,N,N',N'-tetraacetic acid and reduced glutathione. After vortexing, samples were centrifuged at 4°C and the plasma was stored at -70°C until analysis. Plasma catecholamine concentrations were determined by high-performance liquid chromatography with electrochemical detection as previously described (6). Fractions of the eluant were collected into scintillation vials for measurement of [3H]norepinephrine by liquid scintilation counting.

Statistical methods. Data are reported as means ± SE. Mean differences between the young and old subjects were analyzed by using the Students's t-test for normally distributed values and the Mann-Whitney U-test for non-Gaussian data. Significance was defined as P < 0.05.

RESULTS

Peak work capacity, heart rate, and catecholamine responses. Peak work capacity determined from the initial graded exercise test was 253 ± 24 and 122 ± 10 W for young and old subjects, respectively. Maximal heart rates observed during this test were 184 ± 4 and 143 ± 3 beats/min for young and old subjects, respectively. Resting heart rate did not differ between age groups (Table 1). Heart rate increased significantly in response to submaximal exercise for both groups, but again no age differences were observed. Arterial norepinephrine concentrations were significantly greater (+42%) for the old compared with the young group at rest. Norepinephrine concentrations increased significantly in response to exercise for both groups, and, as with rest, the old subjects demonstrated greater norepinephrine concentrations compared with the young group (+46%; Table 1). Although there was a trend for epinephrine values to be higher for the old group, this was only significant when measured in response to exercise (+31%).

Table  1.   Heart rate and arterial catecholamine concentrations measured at rest and in response to 20 min of submaximal exercise
Heart Rate, beats/min
Norepinephrine, ng/ml
Epinephrine, ng/ml
Rest Exercise Rest Exercise Rest Exercise
Young subjects 61 ± 3  123 ± 5dagger 197 ± 27  453 ± 57dagger 52 ± 16  87 ± 21 
Old subjects 66 ± 4  107 ± 5dagger 280 ± 36* 680 ± 85*, dagger 83 ± 14  127 ± 17dagger
Values are means ± SE for 8 young and 7 old subjects. * Significantly different from young subjects, P < 0.05.  dagger Significantly different from resting values, P < 0.05.

Whole body sympathetic activity. Whole body norepinephrine spillover did not differ between groups under resting conditions (Fig. 1). Mean values were 573 ± 89 and 548 ± 36 ng/min for young and old subjects, respectively. In response to 20 min of submaximal exercise, whole body spillover rates increased significantly in both groups compared with resting values (+89 and +121% for young and old subjects, respectively); however, norepinephrine spillover rates during exercise did not differ between age groups.
Fig. 1. Whole body norepinephrine spillover at rest and during 20 min of submaximal supine cycling exercise in young (n = 8; solid bars) and old (n = 7; open bars) subjects. dagger  Significantly different from resting values within an age group, P < 0.05.
[View Larger Version of this Image (11K GIF file)]

Whole body epinephrine secretion rates followed a pattern similar to that found for norepinephrine spillover such that no differences were observed between groups at rest (128 ± 22 and 151 ± 22 ng/min for young and old subjects, respectively). Additionally, epinephrine secretion rates increased significantly with exercise (+90 and +50% for young and old subjects, respectively) with no differences found between age groups (Fig. 2).
Fig. 2. Whole body epinephrine spillover at rest and during 20 min of submaximal supine cycling exercise in young (solid bars) and old subjects (open bars). dagger  Significantly different from resting values within an age group, P < 0.05.
[View Larger Version of this Image (13K GIF file)]

Hepatomesenteric norepinephrine spillover. Hepatomesenteric norepinephrine spillover was significantly greater for old compared with young subjects when measured both at rest and in response to submaximal exercise (Fig. 3). At rest, norepinephrine spillover was increased 50% in the old subjects. Spillover rates were significantly increased during exercise for both groups, with the old subjects still demonstrating significantly greater values compared with the young group (+36%). Hepatomesenteric blood flows, as determined from indocyanine green measurements, did not differ between age groups both at rest (1,031 ± 80 and 1,188 ± 119 ml/min for young and old subjects, respectively) and during exercise (815 ± 69 and 866 ± 104 ml/min, respectively). Reduction in hepatomesenteric flow with exercise represented a decrease of 21 and 27% for young and old subjects, respectively, compared with resting flow.
Fig. 3. Norepinephrine spillover from hepatomesenteric region to plasma. At rest, old subjects (open bars) had 50% greater rates of norepinephrine spillover compared with young subjects (solid bars). During exercise, old subjects had 36% higher spillover rates than did young group. * Significant difference between young and old subjects, P < 0.05. dagger  Significantly different from resting values within an age group, P < 0.05.
[View Larger Version of this Image (13K GIF file)]

Norepinephrine and epinephrine clearance rates. Plasma clearance rates determined at rest for both norepinephrine and epinephrine were significantly lower for the old individuals compared with the young group (Fig. 4, A and B). This decrease in resting clearance rates was similar for both catecholamines measured (-23 and -22% for norepinephrine and epinephrine, respectively). In response to exercise, clearance rates remained significantly lower in old subjects for both norepinephrine (-30%) and epinephrine (-30%) compared with young subjects. Again, no differences in clearance rates between norepinephrine and epinephrine were observed. Last, exercise did not alter clearance rates for norepinephrine compared with resting values in either age group; however, epinephrine clearance rates were significantly increased with exercise for the young subjects only (+22%).
Fig. 4. A: plasma norepinephrine clearance rates at rest and during submaximal exercise. Clearance rates were 23 and 30% lower for old subjects at rest and during exercise, respectively, compared with young subjects. B: plasma epinephrine clearance rates both at rest and during exercise for both age groups. Epinephrine clearance was 22 and 30% lower for old subjects at rest and during exercise, respectively, compared with young subjects. Solid bars, young subjects; open bars, old subjects. * Significant difference between young and old subjects, P < 0.05.
[View Larger Version of this Image (14K GIF file)]

DISCUSSION

The major finding of the present investigation was that in old subjects, a reduction in norepinephrine clearance and an increase in regional norepinephrine spillover can account for the higher plasma norepinephrine concentrations observed at rest. This relationship is not exacerbated by the stress imposed during an acute bout of exercise. Although whole body norepinephrine spillover at rest was not different between the two age groups (Fig. 1), organ-specific differences do exist, as was evident for hepatomesenteric spillover rates (Fig. 3). A 50% increase in the rate of hepatomesenteric norepinephrine spillover was observed for the old subjects. Previous studies examining the influence of age on whole body norepinephrine spillover to plasma have yielded mixed results. Esler et al. (5) found that although plasma norepinephrine concentration was significantly greater in healthy old subjects compared with young subjects, no differences in whole body spillover rates were observed. This is consistent with the results of the present investigation, which used similar techniques. However, two other studies have reported elevated rates of whole body spillover under resting conditions in old subjects (8, 16). Reasons for these differences are uncertain but may be related to the method employed to determine norepinephrine spillover because one study (16) used constant infusions of unlabeled norepinephrine to estimate release rates into the circulation.

Consistent with the results of the present study, other investigations have suggested that there are age-dependent regional differences in sympathetic nerve activity that are tissue specific. The greater rate of norepinephrine spillover from the hepatomesenteric region found for our old subjects has also been observed to occur in the heart. Esler et al. (6) found that an 85% increase in cardiac norepinephrine spillover occurred at rest when old subjects (60-75 yr) were compared with young subjects (20-30 yr). Also, with use of microneurography, increased firing rates of postganglionic sympathetic efferent nerve fibers to skeletal muscle have been repeatedly observed to occur as a result of advancing age (9, 14, 19). However, because other organs such as the kidney and adrenal medulla do not demonstrate any age-related differences in norepinephrine spillover (3, 4, 6), it would appear that increases sympathetic activation and/or outflow with age is not a global phenomenon. These differences in tissue-specific responses with age may also contribute to the variability observed when whole body plasma norepinephrine spillover is measured.

The increase in plasma norepinephrine concentration associated with stressful stimuli has been generally reported to be greater in old vs. young subjects (isometric and dynamic exercise, oral glucose, mental stress; 4, 7, 11, 15, 20, 21). This is commonly considered to represent greater sympathetic nerve activity, perhaps as a result of diminished end-organ responsiveness (10, 12). In our subjects, whole body norepinephrine spillover increased significantly during exercise compared with rest for all individuals, and, similar to rest, spillover rates did not differ between age groups. Thus, on a global level, exercise at the same relative intensity did not elicit a greater increase in norepinephrine spillover in old subjects. This would suggest that, in response to this stressor, whole body sympathetic nerve activity did not differ between age groups. However, during exercise, hepatomesenteric spillover rates continued to be significantly greater for old subjects. It should be noted that the magnitude of this response did not differ from resting values. Thus, while it is clear that age-related regional differences exist in norepinephrine spillover rates, these differences were not exacerbated during exercise.

It is important to note that the primary factor determining the magnitude of the sympathetic response during an acute bout of exercise, and, subsequently, the arterial catecholamine content, is the relative intensity (7, 11, 12). That the exercise stimulus was of the same relative magnitude between the two age groups studied in this investigation is supported by the following data. In terms of power output, the young group was exercising at 53.7% of their maximal capacity (maximal = 253 ± 24 W, submaximal = 136 ± 9 W). A similar comparison for the old subjects indicates that they were working at 49.2% of maximal capacity. In terms of heart rate, when one calculates the percentage of heart rate reserve that both groups were exercising, it is found that young subjects were at 50.4% of maximal heart rate reserve while the old subjects were at 52.6%. Thus, in terms of both power output and heart rate reserve, both groups were exercising at similar relative workloads.

Whether the age-related increase in norepinephrine overflow to the circulation is due to elevated rates of sympathetic nerve firing or is a result of impaired neuronal reuptake of norepinephrine cannot be determined from the present study. Evidence exists to suggest that both mechanisms may be contributing to the increase in spillover rates observed. Direct microneurographic measurements of the peroneal nerve indicate that resting muscle sympathetic nerve activity is increased with advancing age, suggesting that actual sympathetic firing (burst frequency and incidence) increases with age (9, 14, 19). This increase in muscle sympathetic nerve activity is present in healthy old individuals, thus appearing to be associated with the aging process per se and independent of age-related disease (14). However, when other tissues are examined, evidence for faulty neuronal reuptake of norepinephrine is found. Esler et al. (6) concluded that despite the significant increase in norepinephrine spillover from the heart in old men, diminished transmitter reuptake rather than increased cardiac sympathetic nerve activity was responsible. Tritiated norepinephrine extraction from plasma during transit through the heart was lower with age, suggesting reduced norepinephrine reuptake. Additionally, overflow of norepinephrine precursors from heart was normal, indicating that norepinephrine synthesis and release were not impaired with age. A similar conclusion was reached by Hoeldtke and Cilmi (8), who reported that despite a greater rate of norepinephrine secretion into plasma in old healthy subjects, tissue norepinephrine production was normal, suggesting a defect in storage and/or reuptake of the transmitter.

Our results provide evidence that the increase in plasma norepinephrine content associated with advancing age is primarily a function of a reduction in the ability to clear the catecholamines from the circulation. The 23% reduction found in this study for norepinephrine clearance rates is in agreement with other studies reporting significant age-related declines in clearance ranging from 16 to 25% (4, 5, 13, 17). Only one study did not find this decline to be significant (-15%; 16). Interestingly, when measuring renal norepinephrine clearance rates as a function of age, Esler et al. (4) found that clearance of norepinephrine by the kidneys decreased with age (-21%) by the same magnitude as that determined for whole body clearance.

During exercise, despite the fact that norepinephrine spillover rates increased significantly above resting values for all subjects, norepinephrine clearance rates did not change from values measured at rest. Consequently, arterial norepinephrine concentration increased proportionally during exercise because clearance from plasma did not increase to keep pace with the rise in release into the circulation. As witnessed when the subjects were at rest, plasma norepinephrine clearance was suppressed for old subjects during exercise; thus arterial norepinephrine concentration remained greater in old vs. young subjects during exercise. The inability for clearance rates to increase to match the rise in norepinephrine spillover during exercise can account entirely for the changes observed in circulating catecholamine content for both age groups. More importantly, because no age differences were found in whole body norepinephrine spillover rates when measured both at rest and during exercise, this would suggest that, in our subjects, the decrease in clearance rates was the primary factor responsible for the elevation in plasma norepinephrine concentrations associated with age. Thus, if the rate at which norepinephrine enters the circulation is not different (on a whole body level) between groups, then the decline in the rate of removal must be the main reason for greater plasma norepinephrine concentrations found with advancing age.

Whether measured at rest or during exercise, plasma clearance rates for epinephrine did not differ significantly from those found for norepinephrine. This was true across age groups; thus epinephrine clearance rates, like those of norepinephrine, were lower in old vs. young subjects (-22 and -30% for rest and exercise, respectively). A strong inverse correlation existed between epinephrine clearance rates and arterial epinephrine concentration. It has been suggested that both epinephrine and norepinephrine are cleared through beta -adrenergic mechanisms in humans (1). This may, in part, account for our findings that 1 ) plasma clearance rates for both epinephrine and norepinephrine were identical when measured at rest and during exercise, and 2 ) the magnitude of the age-related decline in clearance was also similar between these two catecholamines. If both epinephrine and norepinephrine are cleared from the circulation by identical mechanisms, then one would expect that any perturbation to the system (exercise, aging) would affect these catecholamines in a similar fashion. Additionally, as beta -adrenergic responsiveness is well documented to decline with age in many organ systems (10, 12), it is possible that this may contribute to the age-related decline in the ability for catecholamine clearance from the circulation.

ACKNOWLEDGEMENTS

The authors thank Andrea Turner and Helen Cox for technical assistance.

FOOTNOTES

Address for reprint requests: R. S. Mazzeo, Univ. of Colorado, Dept. of Kinesiology, Box 354, Boulder, CO 80309-0354.

Received 26 November 1996; accepted in final form 20 February 1997.

REFERENCES

1. Cryer, P. E., R. A. Rizza, M. W. Haymond, and J. E. Gerich. Epinephrine and norepinephrine are cleared through beta-adrenergic, but not alpha-adrenergic, mechanisms in man. Metabolism 29: 1114-1118, 1980 . [Medline]
2. Esler, M., G. Jennings, P. Korner, P. Blomberry, N. Sacharias, and P. Leonard. Measurement of total and organ-specific norepinephrine kinetics in humans. Am. J. Physiol. 247 (Endocrinol. Metab. 10): E21-E28, 1984 . [Abstract/Free Full Text]
3. Esler, M., D. Kaye, J. Thompson, G. Jennings, H. Cox, A. Turner, G. Lambert, and D. Seals. Effects of aging on epinephrine secretion and regional release of epinephrine from the human heart. J. Clin. Endocrinol. Metab. 80: 435-442, 1995 . [Abstract]
4. Esler, M., G. Lambert, and G. Jennings. The influence of aging on catecholamine metabolism. In: Handbook of Hypertension, edited by A. Amery, and J. Staessen. New York: Elsevier, 1989, vol. 12, p. 85-98.
5. Esler, M., H. Skews, P. Leonard, G. Jackman, A. Bobik, and P. Korner. Age-dependence of noradrenaline kinetics in normal subjects. Clin. Sci. Lond. 60: 217-219, 1981 . [Medline]
6. Esler, M. D., A. G. Turner, D. M. Kaye, J. M. Thompson, B. A. Kingwell, M. Morris, G. W. Lambert, G. L. Jennings, H. S. Cox, and D. R. Seals. Aging effects on human sympathetic neuronal function. Am. J. Physiol. 268 (Regulatory Intregrative Comp. Physiol 57): R278-R285, 1995 . [Abstract/Free Full Text]
7. Fleg, J. L., S. P. Tzankoff, and E. G. Lakatta. Age-related augmentation of plasma catecholamines during dynamic exercise in healthy males. J. Appl. Physiol. 59: 1033-1039, 1985 [Abstract/Free Full Text] .
8. Hoeldtke, R. D., and K. M. Cilmi. Effects of aging on catecholamine metabolism. J. Clin. Endocrinol. Metab. 60: 479-484, 1985 . [Abstract/Free Full Text]
9. Iwase, S., T. Mano, T. Watanabe, M. Saito, and F. Kobayashi. Age-related changes of sympathetic outflow to muscles in humans. J. Gerontol. 46: M1-M5, 1991 . [Abstract]
10. Lakatta, E. G., G. Gerstenblith, C. S. Angell, N. W. Shock, and M. L. Weisfeldt. Diminished inotropic response of aged myocardium to catecholamines. Circ. Res. 36: 262-269, 1975 . [Abstract/Free Full Text]
11. Lehmann, M., and J. Keul. Age-associated changes of exercise-induced plasma catecholamine responses. Eur. J. Appl. Physiol. Occup. Physiol. 55: 302-306, 1986. [Medline]
12. Mazzeo, R. S., and P. A. Grantham. Sympathetic response to exercise in various tissues with advancing age. J. Appl. Physiol. 66: 1506-1508, 1989 [Abstract/Free Full Text] .
13. Morrow, L. A., O. A. Linares, T. J. Hill, J. A. Sanfield, M. A. Supiano, S. G. Rosen, and J. B. Halter. Age differences in the plasma clearance mechanisms for epinephrine and norepinephrine in humans. J. Clin. Endocrinol. Metab. 65: 508-511, 1987 . [Abstract/Free Full Text]
14. Ng, A. V., R. Callister, D. G. Johnson, and D. R. Seals. Age and gender influence muscle sympathetic nerve activity at rest in healthy humans. Hypertension 21: 498-503, 1993 . [Abstract/Free Full Text]
15. Palmer, G. J., M. G. Ziegler, and C. R. Lake. Response of norepinephrine and blood pressure to stress increases with age. J. Gerontol. 33: 482-487, 1978 . [Abstract/Free Full Text]
16. Rubin, P. C., P. J. W. Scott, K. McLean, and J. L. Reid. Noradrenaline release and clearance in relation to age and blood pressure in man. Eur. J. Clin. Invest. 12: 121-125, 1982 . [Medline]
17. Veith, R. C., J. A. Featherstone, O. A. Linares, and J. B. Halter. Age differences in plasma norepinephrine kinetics in humans. J. Gerontol. 41: 319-324, 1986 . [Abstract/Free Full Text]
18. Wallin, B. G., and G. Sundlof. A quantitative study of muscle nerve sympathetic activity in resting normotensive and hypertensive subjects. Hypertension 1: 67-77, 1979 . [Abstract/Free Full Text]
19. Yamada, Y., E. Miyajima, O. Tochikubo, T. Matsukawa, and M. Ishii. Age-related changes in muscle sympathetic nerve activity in essential hypertension. Hypertension 13: 870-877, 1989 . [Abstract/Free Full Text]
20. Young, J. B., J. W. Rowe, J. A. Pallotta, D. Sparrow, and L. Landsberg. Enhanced plasma norepinephrine response to upright posture and oral glucose administration in elderly human subjects. Metabolism 29: 532-539, 1980 . [Medline]
21. Ziegler, M. G., C. R. Lake, and I. J. Kopin. Plasma norepinephrine increases with age. Nature 261: 333-335, 1976 . [Medline]
0161-7567/97 $5.00 Copyright © 1997 the American Physiological Society


This article has been cited by other articles:


Home page
 J. Appl. Physiol.Home page
D. N. French, W. J. Kraemer, J. S. Volek, B. A. Spiering, D. A. Judelson, J. R. Hoffman, and C. M. Maresh
Anticipatory responses of catecholamines on muscle force production
J Appl Physiol, January 1, 2007; 102(1): 94 - 102.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
K. Takeshita, T. Fujimori, Y. Kurotaki, H. Honjo, H. Tsujikawa, K. Yasui, J.-K. Lee, K. Kamiya, K. Kitaichi, K. Yamamoto, et al.
Sinoatrial Node Dysfunction and Early Unexpected Death of Mice With a Defect of klotho Gene Expression
Circulation, April 13, 2004; 109(14): 1776 - 1782.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
D. R. Seals and C. Bell
Chronic Sympathetic Activation: Consequence and Cause of Age-Associated Obesity?
Diabetes, February 1, 2004; 53(2): 276 - 284.
[Abstract] [Full Text]

Home page
 J. Physiol.Home page
D. W Koch, U. A Leuenberger, and D. N Proctor
Augmented leg vasoconstriction in dynamically exercising older men during acute sympathetic stimulation
J. Physiol., August 15, 2003; 551(1): 337 - 344.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
D. R Seals and M. D Esler
Human ageing and the sympathoadrenal system
J. Physiol., November 1, 2000; 528(3): 407 - 417.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
H. M. Perry III
The Endocrinology of Aging
Clin. Chem., August 1, 1999; 45(8): 1369 - 1376.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
S. G. Khasar, G. McCarter, and J. D. Levine
Epinephrine Produces a beta -Adrenergic Receptor-Mediated Mechanical Hyperalgesia and In Vitro Sensitization of Rat Nociceptors
J Neurophysiol, March 1, 1999; 81(3): 1104 - 1112.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
D. N. Proctor, P. H. Shen, N. M. Dietz, T. J. Eickhoff, L. A. Lawler, E. J. Ebersold, D. L. Loeffler, and M. J. Joyner
Reduced leg blood flow during dynamic exercise in older endurance-trained men
J Appl Physiol, July 1, 1998; 85(1): 68 - 75.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
G. G. Neri Serneri, M. Boddi, P. A. Modesti, I. Cecioni, M. Coppo, L. Padeletti, A. Michelucci, A. Colella, and G. Galanti
Increased Cardiac Sympathetic Activity and Insulin-Like Growth Factor-I Formation Are Associated With Physiological Hypertrophy in Athletes
Circ. Res., November 23, 2001; 89(11): 977 - 982.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mazzeo, R. S.
Right arrow Articles by Esler, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mazzeo, R. S.
Right arrow Articles by Esler, M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online