Norepinephrine: hormone and neurotransmitter in man.

Silverberg, Alan B.; Shah, Suresh D.; Haymond, Morey W.; Cryer, Philip E.

doi:10.1152/ajpendo.1978.234.3.e252

Cited by 210 publications

(136 citation statements)

References 22 publications

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“…NE not only raises blood pressure but also increases myocardial 0 2 consumption, activates platelets, accelerates ventricular remodeling, induces myocyte apoptosis, and is arrythmogenic. Although the plasma concentrations noted here appear to be below the threshold for any direct cardiovascular or vascular effects, it is the much higher intrasynaptic concentrations associated with such elevations in plasma NE that are cardiotoxic (21).…”

Section: Study Of Arterial Ne-appearance Rate In Mild͞moderate Depresmentioning

confidence: 51%

Cardiac implications of increased arterial entry and reversible 24-h central and peripheral norepinephrine levels in melancholia

Gold

Wong

Goldstein

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The mortality of chronic heart failure (CHF) doubles either when CHF patients are depressed or when their plasma norepinephrine (NE) level exceeds those of controls by Ϸ40%. We hypothesized that patients with major depression had centrally driven, sustained, stress-related, and treatment-reversible increases in plasma NE capable of increasing mortality in CHF patients with depression. We studied 23 controls and 22 medication-free patients with melancholic depression. In severely depressed patients before and after electroconvulsive therapy (ECT), we measured cerebrospinal fluid (CSF) NE, plasma NE, plasma epinephrine (EPI), and plasma cortisol hourly for 30 h. In mildly-to-moderately depressed melancholic patients, we assessed basal and stress-mediated arterial NE appearance. Severely depressed patients had significant increases in mean around-the-clock levels of CSF NE (P < 0.02), plasma NE (P < 0.02), plasma EPI (P < 0.02), and plasma cortisol (P < 0.02). CSF NE, plasma NE, and cortisol all rose together throughout the night and peaked in the morning. Each fell to control values after ECT. Mildly-to-moderately melancholic patients also had increased basal (P < 0.05) and stress-related (P < 0.03) arterial NE-appearance rates. Severely melancholic depressed, medication-free patients had around-the-clock increases in plasma NE levels capable of increasing mortality in CHF. Twenty-four-hour indices of central noradrenergic, adrenomedullary, and adrenocortical secretion were also elevated. Concurrent diurnal rhythms of these secretions could potentiate their cardiotoxicity. Even mildly-to-moderately depressed melancholic patients had clinically relevant increases in the arterial NE-appearance rate. These findings will not apply to all clinical subtypes of major depression.cerebrospinal fluid ͉ epinephrine ͉ major depression ͉ cardiovascular disease ͉ chronic heart failure T he coexistence of major depression with chronic heart failure (CHF) doubles the mortality of CHF (1-3). CHF patients with asymptomatic left ventricular dysfunction coupled with high plasma norepinephrine (NE) levels also have a doubling in mortality (4). In one study, plasma NE levels equal to 40% or greater than those in their controls also doubled CHF mortality (5). Even a modest (25%) increase in plasma NE levels over 4 months more than doubled mortality in CHF patients (6). Prior studies have shown that elevated NE levels in patients with CHF can be further increased in an additive fashion by the superimposition of complications known to be associated with increased NE levels (7). Thus, substantially increased NE release in depression would result in significant increases in the burden of NE hypersecretion in patients with CHF who become depressed.Evidence of increased NE secretion in major depression could help explain increased mortality in patients with CHF who are depressed. However, results from prior studies of NE secretion in depression have been contradictory (reviewed in ref. 8). This ambiguity is likely to reflect almost exclusive ...

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Section: Study Of Arterial Ne-appearance Rate In Mild͞moderate Depresmentioning

confidence: 51%

Cardiac implications of increased arterial entry and reversible 24-h central and peripheral norepinephrine levels in melancholia

Gold

Wong

Goldstein

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…21 We have measured the effect of a 12 week course of sibutramine, a serotonin and noradrenaline reuptake inhibitor, on REE and adrenaline induced thermogenesis in 10 obese females and compared the results in 9 obese females receiving a placebo for the same period. Nordrenaline exerts its physiological effects mainly as a neurotransmitter 22 and its metabolic effects as a circulating hormone are only found with exceedingly high plasma concentrations, for example, during prolonged maximal exercise or severe illness like myocardial infarction. 22,23 During hormone infusions, the plasma threshold concentration for cardiovascular and metabolic changes is about 10 times lower for adrenaline than for noradrenaline.…”

Section: Discussionmentioning

confidence: 99%

“…Nordrenaline exerts its physiological effects mainly as a neurotransmitter 22 and its metabolic effects as a circulating hormone are only found with exceedingly high plasma concentrations, for example, during prolonged maximal exercise or severe illness like myocardial infarction. 22,23 During hormone infusions, the plasma threshold concentration for cardiovascular and metabolic changes is about 10 times lower for adrenaline than for noradrenaline. 10,22 Thus, it is impossible to mimic physiological events completely by noradrenaline infusions, and for these reasons adrenaline was chosen for the present study.…”

Section: Discussionmentioning

confidence: 99%

“…22,23 During hormone infusions, the plasma threshold concentration for cardiovascular and metabolic changes is about 10 times lower for adrenaline than for noradrenaline. 10,22 Thus, it is impossible to mimic physiological events completely by noradrenaline infusions, and for these reasons adrenaline was chosen for the present study. The threshold for metabolic effects observed during adrenaline infusion in this experiment was well below the concentrations observed during ordinary activities like standing or mild exercise.…”

Section: Discussionmentioning

confidence: 99%

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The effect of sibutramine on resting energy expenditure and adrenaline-induced thermogenesis in obese females

1999

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BACKGROUND: Sibutramine, an inhibitor of serotonin and noradrenaline uptake, reduces appetite to cause weight loss. This study tested the hypothesis that an increase in energy expenditure also contributes to this weight loss. In addition, the effects of sibutramine on adrenaline induced changes in heart rate and cardiac output were determined METHODS: Nineteen obese females randomly received either sibutramine 15 mg daily or placebo for 12 weeks along with dietary advice. Resting energy expenditure (REE) was measured and then energy expenditure was measured during a 30 min infusion of adrenaline (25 ngaminakg IBW). Cardiac output and heart rate, measured by Duplex Colour Doppler ultrasonography, were similarly measured in the basal state and post adrenaline. All measurements were recorded at baseline and then after 12 weeks. RESULTS: Ten patients who received sibutramine reduced their weight by 8.1 AE 3.8% while 9 placebo treated subjects reduced their weight by 5.1 AE 4.4%, P 0.13. In absolute terms, REE decreased in placebo subjects from 1500 AE 201 kcala24 h to 1357 AE 231 kcala24 h (9.4 AE 9.9%) and in sibutramine subjects from 1540 AE 184 kcala24 h to 1444 AE 128 kcala24 h (5.3 AE 12.0%), P 0.77. The increased weight loss in the sibutramine group was associated with an increase in the FFM adjusted REE (2.2 AE 16.1%) unlike the expected decrease (5.8 AE 9.5%) in the placebo group (P 0.11). There was some suggestion (P 0.09) that the usual positive correlation between loss of weight and decline in REE was lost in the sibutramine group (r 7 0.30) compared with placebo (r 0.35). There was a negative correlation between loss of FFM and decline in REEakg FFM and (P 0.029) which was not evident in placebo (P 0.83). Adrenaline induced energy expenditure was similar in the two groups at the end of the 12 week period and there were no signi®cant cardiovascular changes between the two groups. CONCLUSIONS: Sibutramine limits the decline in REE associated with weight loss, equivalent to about 100 kcalad. This could allow greater numbers of people to maintain a greater degree of weight loss.

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“…Results of these studies have largely focused on two particular features: histological evidence of myocarditis (catecholamine cardiomyopathy) 28 " 31 and demonstration of hypertension and bradycardia. 20 -2I -32~34 To determine threshold levels for its metabolic effects, Silverberg et al 35 infused NE in stepwise fashion in doses from 0.1 to 5 ^.g/min over 60 minutes. At the highest dose in these short-term studies (plasma levels of 2150 ± 66 pg/ml), systolic and diastolic arterial blood pressures rose while HR fell.…”

Section: Discussionmentioning

confidence: 99%

Absence of hypertension despite chronic marked elevations in plasma norepinephrine in conscious dogs.

King¹,

Sack²,

Kichuk³

et al. 1987

Hypertension

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SUMMARY To better define the mechanisms of blood pressure control in states of catecholamine excess, we infused norepinephrine for 28 days using subcutaneously implanted osmotic pumps in dogs previously instrumented for monitoring left ventricular dynamics and cardiac output. Plasma norepinephrine rose from 238 ± 27 to 4346 ± 952 pg/ml at 21 days, while epinephrine and dopamine levels did not change. Heart rate fell from 85 ± 4 to 63 ± 6 beats/min, while arterial pressure was unchanged from baseline. Total peripheral resistance rose 0.011 ± 0.003 mm Hg/ml/min from a control value of 0.029 ± 0.002 mm Hg/ml/min, and cardiac output decreased 1093 ± 292 ml/min from a baseline level of 3575 ± 156 ml/min. Since stroke volume did not change, the maintenance of arterial pressure is related to decreases in cardiac output secondary to bradycardia. Buffering mechanisms are responsible for maintenance of systemic arterial pressure because hexamethonium and atropine caused hypertension. Although left ventricular end-diastolic pressure, end-diastolic diameter, shortening, rate of change of pressure, velocity of myocardial shortening, cardiac work, stroke work, and the double product did not change significantly during the study, postmortem examination demonstrated biventricular hypertrophy. Thus, despite markedly elevated catecholamine levels and no elevation of systemic arterial pressure, myocardial hypertrophy developed. These studies lend support to the hypothesis that norepinephrine may be a direct myocardial tropic hormone and suggest that intense activation of reflex buffering mechanisms maintains blood pressure in the normal range during chronic catecholamine infusion. (Hypertension 9: 582-590, 1987) KEY WORDS • bradycardia • hypertension • hypertrophy • catecholamines • total peripheral resistance • atropine E LEVATIONS in catecholamine levels may be associated with a number of disease states, including mitral valve prolapse (MVP), 1 -2 chronic myocardial failure, 3 " 6 and pheochromocytoma. 7 These disease states may be characterized by sustained or episodic hypertension, myocardial dysfunction, and cardiomyopathy.Recently, it has been noted that certain patients with MVP, chronic myocardial failure, or pheochromocytoma have dysautonomia, manifested by abnormalities in heart rate or blood pressure response (or both) to orthostatic change or exercise. 8 " 12 Some investigations of patients with MVP having dysautonomia are consistent with evidence of hyperadrenergic states and some with simultaneous hypervagatonia. 9 -13 Significant elevations in serum catecholamine levels have been observed in a group of symptomatic patients with MVP 1 ' l4 ; these results have been confirmed by other workers. 2 ' 8> l5 Patients with chronic myocardial failure, regardless of etiology, have elevated plasma norepinephrine (NE) levels. 16 In addition, defects in baroreceptor reflex-mediated vasoconstrictor responses have been noted in dogs 17 and in patients 18 -19 with marked myocardial dysfunction.Several studies, summarized by Ec...

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Norepinephrine: hormone and neurotransmitter in man.

Cited by 210 publications

References 22 publications

Cardiac implications of increased arterial entry and reversible 24-h central and peripheral norepinephrine levels in melancholia

Cardiac implications of increased arterial entry and reversible 24-h central and peripheral norepinephrine levels in melancholia

The effect of sibutramine on resting energy expenditure and adrenaline-induced thermogenesis in obese females

Absence of hypertension despite chronic marked elevations in plasma norepinephrine in conscious dogs.

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