Age-Dependence of Noradrenaline Kinetics in Normal Subjects

Esler, Murray; Skews, Helen; Leonard, P; Jackman, Graham P.; Bobik, Alex; Korner, Paul I.

doi:10.1042/cs0600217

Cited by 159 publications

(45 citation statements)

References 5 publications

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“…Plasma norepinephrine concentrations increase with age, by approximately 13% per decade. 1'-19 In our experience, this relationship reflects reduced clearance with increasing age, 19 although others have reported that total norepinephrine spillover is higher in the elderly.20 Although age may affect norepinephrine kinetics to some degree, it is most unlikely that the marked increases we have demonstrated in total, cardiac, and renal spillover in heart failure are the result of this influence.…”

Section: Discussionmentioning

confidence: 66%

Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity.

Hasking¹,

Esler²,

Jennings³

et al. 1986

Circulation

845

434

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The analysis of plasma kinetics of the sympathetic neurotransmitter norepinephrine can be used to estimate sympathetic nervous "activity" (integrated nerve firing rate) for the body as a whole and for individual organs. In 12 patients with cardiac failure (left ventricular ejection fraction 10% to 39%), the mean arterial plasma norepinephrine concentration was 557 + 68 pg/ml (mean SE) compared with 211 + 21 pg/ml in 15 subjects without heart failure (p < .002). The difference was due to both increased release of norepinephrine to plasma (indicating increased "total" sympathetic activity) and reduced clearance of norepinephrine from plasma. The increase in sympathetic activity did not involve all organs equally. Cardiac (32 ± 9 vs 5 ± 1 ng/min; p < .002) and renal (202 ± 45 vs 66 ± 9 ng/min; p = .002) norepinephrine spillover were increased by 540% and 206%, respectively, but norepinephrine spillover from the lungs was normal. Adrenomedullary activity was also increased in the patients with heart failure, whose mean arterial plasma epinephrine concentration was 181 + 38 pg/ml compared with 71 ± 12 pg/ml in control subjects (p < .02). There is marked regional variation, inapparent from measurements of plasma norepinephrine concentration, in sympathetic nerve activity in patients with congestive heart failure. The finding of increased cardiorenal norepinephrine spillover has important pathophysiologic and therapeutic implications. Circulation 73, No. 4, 615421, 1986. THE CONSENSUS that sympathetic nervous overactivity is important in the pathophysiology of congestive heart failure is based in part on observations that the sympathetic neurotransmitter norepinephrine is present in plasma at increased concentration.1 The plasma concentration of norepinephrine, however, is determined by the rates of both release of norepinephrine to plasma and removal of norepinephrine from plasma. Norepinephrine plasma clearance might be reduced, and the plasma concentration thereby increased, because of the reduced cardiac output and organ blood flows that accompany congestive heart failure. A second difficulty in the study of the role of the sympathetic nervous system in congestive heart failure has been the inability of clinical research methods to estimate sympathetic activity in internal organs. Microneurographic electrophysiologic methods are available for the clinical study of nerve firing rates in subcutaneous nerves supplying skin and skeletal muscle,2 but the nerves to internal organs are not accessible for such testing.Measurement of sympathetic transmitter release is an alternative technique for quantifying sympathetic nerve activity in internal organs. We have developed a method3 using infusions of tritiated norepinephrine to determine both the rate at which norepinephrine spills into plasma and its rate of clearance from plasma. The technique has recently been applied to determine the rates of norepinephrine spillover from individual organs.4Although only a small fraction of the norepinephrine

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Section: Discussionmentioning

confidence: 66%

Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity.

Hasking¹,

Esler²,

Jennings³

et al. 1986

Circulation

845

434

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“…Elevated levels of plasma NE may reflect an age-related increase ofNE spillover rate (36). Factors such as a decrease in the metabolic clearance rate cannot be excluded (16). Therefore it is questionable whether the NE levels in the aged animals reflect a different pattern of NE release and altered sympathetic nerve activity.…”

Section: Discussionmentioning

confidence: 99%

Conditioned neuroendocrine and cardiovascular stress responsiveness accompanying behavioral passivity and activity in aged and in young rats

Korte

Buwalda

Bouws

et al. 1992

Physiology & Behavior

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Conditionedneuroendocrine and cardiovascular stress responsiveness accompanying behavioral passivity and activity in aged and in young rats. PHYSIOL BEHAV 51(4) 815-822, 1992.--Mean arterial pressure (MAP), heart rate (HR), plasma epinephrine (E), plasma norepinephrine (NE), and plasma corticosterone (CORT) were measured in 3-month-and 24-month-old male Wistar rats exposed to a conditioned emotional stress response (CER) paradigm and a conditioned defensive burying (CDB) paradigm. In the CER situation blood samples were taken during reexposure to the training environment one day after a single inescapable footshock (0.6 mA, AC for 3 s) had been administered. In the CER paradigm the young rats displayed passive behavior (immobility) accompanied by an increase in plasma levels of CORT and E, whereas both the control and conditioned animals showed increased NE responses. Previously shocked aged rats exhibited an attenuated plasma NE response, whereas levels of E remained elevated to a greater extent. Aged animals showed elevated basal levels of CORT one day after footshock administration. Stress-induced immobility was preserved in the aged rats. These animals had an increase in basal MAP values and a decrease in basal HR values compared to young ones.In the CDB paradigm, rats were exposed to a nonelectrified probe 1 day after the repeated shock (2 mA/contact) procedure. Young rats displayed defensive burying accompanied by increments in MAP, HR, CORT, and NE. The aged animals showed similar hormonal, autonomic, and behavioral stress responses.Thus, the age-related alterations in neuroendocrine and autonomic response patterns are apparent in stressed animals during behavioral passivity in absence of control (CER) rather than during active control (defensive burying).

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“…5 The increase in NE with advancing age instead could reflect a compensatory mechanism to a declining peripheral response to adrenergic stimuli 6 -7 or an age-related decrease in clearance of NE. 8 Moreover, a recent study based on single NE samples obtained from a large number of subjects with a wide age range concluded that NE increases with age in normotensive subjects but not in subjects with essential hypertension. 9 However, there is relatively little direct information about the state of plasma catecholamines in hypertension of the elderly.…”

Section: Essential Hypertension • Catecholamines Norepinephrine • Epimentioning

confidence: 99%

Dissociation of 24-hour catecholamine levels from blood pressure in older men.

Stern¹,

Beahm²,

McGinty³

et al. 1985

Hypertension

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SUMMARY Increased plasma norepinephrine levels have been observed in some persons with early essential hypertension. Although both plasma norepinephrine level and mean arterial blood pressure rise with age, little is known about the state of catecholamine secretion in elderly patients with essential hypertension. We studied the 24-hour cycle levels of plasma norepinephrine, epinephrine, and dopamine in 12 elderly hypertensive subjects and 13 age-matched normotensive controls (mean ages, 63.8 ± 1.2 yr and 64.8 ± 1.8 yr [SEM] respectively). Blood samples were obtained at bihourly intervals from 0900 to 2100 hours and every 30 minutes from 2100 to 0900 hours, during which time sleep and breathing were continuously monitored. A circadian rhythm was displayed in both groups by plasma epinephrine levels (mesor, 49 ± 2 pg/ml and 38 ± 1 pg/ml; amplitude, 15 ± 2 pg/ml and 11 ± 1 pg/ml; acrophase, 12.20 ± 0.40 hr and 14.41 ± 0.34 hr in the normotensive and hypertensive groups respectively) but not by plasma norepinephrine or dopamine levels. During the 24-hour cycle plasma epinephrine, but not norepinephrine or dopamine, levels were positively related to mean arterial blood pressure (r = 0.60 for the normotensive subjects, r = 0.57 for the hypertensive subjects, p < 0.01 for both). Mean 24-hour plasma norepinephrine (377 ± 9 pg/ml vs 455 ± 9 pg/ml; p < 0.001), epinephrine (34 ± 2 pg/ml vs 45 ± 2 pg/ml; p < 0.01), and dopamine (40 ± 2 pg/ml vs 62 ± 3 pg/ml; p < 0.01) levels were lower in the hypertensive group, although groups did not differ in parameters known to affect catecholamine secretion such as body weight, sodium intake, sleep efficiency, or sleeprelated breathing disorders. Mean 24-hour plasma norepinephrine level was inversely related to the 24-hour mean arterial blood pressure (r = -0.48, p < 0.05). High norepinephrine levels in the elderly may reflect decreased baroreceptor sensitivity as well as compensatory response to decreased /3-adrenergic receptor sensitivity. It is unclear why elderly hypertensive persons, unlike younger hypertensive persons, have lower plasma catecholamine levels than do elderly normotensive persons. Whereas increased sympathetic outflow has been implicated in the induction of early "neurogenic" essential hypertension, 4 the age-dependent increase in NE is observed in normotensive subjects. Whether the ob- served increment in circulating NE is related to the age-associated rise in blood pressure or to the increased incidence of hypertension in aging humans is unclear. 5 The increase in NE with advancing age instead could reflect a compensatory mechanism to a declining peripheral response to adrenergic stimuli 6 -7 or an age-related decrease in clearance of NE. 8 Moreover, a recent study based on single NE samples obtained from a large number of subjects with a wide age range concluded that NE increases with age in normotensive subjects but not in subjects with essential hypertension. 9 However, there is relatively little direct information about the state of plasma catecholamines in...

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Age-Dependence of Noradrenaline Kinetics in Normal Subjects

Cited by 159 publications

References 5 publications

Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity.

Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity.

Conditioned neuroendocrine and cardiovascular stress responsiveness accompanying behavioral passivity and activity in aged and in young rats

Dissociation of 24-hour catecholamine levels from blood pressure in older men.

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