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1.  Free adrenaline and noradrenaline excretion related to occupational stress. 
British Heart Journal  1979;42(4):471-474.
Urinary levels of free adrenaline and noradrenaline were measured in two groups of healthy male industrial workers exposed to alternate four-day periods of working conditions with and without time stress, to test the hypothesis that the sympathetic nervous system is overactivated by occupational stress. Thirty confectionary workers alternated piece-work (payment by results) and work with a fixed daily wage while 30 metal workers alternated work on an assembly line with work off it. Under time stress urinary free adrenaline was 450 per cent and noradrenaline 230 per cent of the levels for similar work without time stress but involving equal oxygen consumption. These differences were statistically highly significant and they persisted on retesting after six months of alternating work regimens. They support the concept that occupational stress in industrial workers influences the adrenosympathetic system and they indicate a possible method for assessing the effects of high levels of sympathetic activity on the aetiology of ischaemic heart disease.
PMCID: PMC482184  PMID: 508478
2.  Lorry drivers' work stress evaluated by catecholamines excreted in urine. 
OBJECTIVES--To evaluate lorry drivers' work stress by measurement of adrenaline and noradrenaline excreted in the urine, and to find out which factors in their working situation are related to the excretion rates of these catecholamines. METHODS--The urinary excretion of adrenaline and noradrenaline of 32 lorry drivers, who also had loading and unloading activities to perform, was studied for one working day and one rest day. Each driver was asked to provide six urine samples on both days. RESULTS--For all samples, except the first (overnight) sample, the excretion rates of both catecholamines on the working day were higher than those on the rest day. Hierarchical multiple regression analyses were carried out to find out which factors in the drivers' working situation were related to the excretion rate of the working day. The excretion rate of adrenaline on the rest day, age, and psychosomatic complaints were positively related to the excretion rate on the working day (all P < 0.05). Body mass index and physical workload during loading and unloading were positively related to noradrenaline excretion rate (both P < 0.01). Psychosocial job strain did not significantly contribute to the proportion of variance explained in the excretion rates of both catecholamines. CONCLUSIONS--The excretion rates of adrenaline and, especially, noradrenaline on the working day were higher than those found in earlier studies among professional drivers and insufficient recovery took place after the work was ended. The only association between excretion rate on the working day and work stressors was found for noradrenaline and physical workload. The drivers' sympathoadrenal medullary reactivity to everyday work demands shows the characteristics of sustained activation.
PMCID: PMC1128265  PMID: 7670621
3.  Effect of ethylene glycol dinitrate on metabolism of catecholamines and on blood pressure reaction to re-exposure 
Minami, M., Okada, A., Takizawa, A., and Kubota, J. (1972).Brit. J. industr. Med.,29, 321-327. Effect of ethylene glycol dinitrate on metabolism of catecholamines and on blood pressure reaction to re-exposure. Male Donryu rats were divided into two groups. One group was given 65 mg/kg per day of ethylene glycol dinitrate (EGDN) subcutaneously for five days and the other group received the same for 10 days. On the first, second, third, fourth, and fifth days after the last injection of EGDN catecholamines were estimated in the heart, brain, and adrenals and plasma 11-hydroxycorticosteroids and haemoglobin were estimated in blood. Urine samples were collected for 24 hours every other day before, during, and after the period of EGDN injection.
After five successive doses of EGDN the concentration of catecholamines in the organs increased and urinary catecholamine excretion was a little greater than from the controls. Reinjection of EGDN caused prolonged irreversible depression of the blood pressure.
After 10 successive doses of EGDN the concentrations of catecholamines in the organs were normal, but noradrenaline excretion in the urine was increased for three days. Reinjection of EGDN on the first day caused prolonged depression of blood pressure, but by five days the response had returned to the more transient depression observed in the controls.
The probability of coronary spasm is considered to be greater in the condition found after five than in that after 10 successive injections because more noradrenaline was available in the cardiac muscle as well as adrenaline in the adrenals.
After 10 successive injections the increased noradrenaline concentration in the urine reflected the raised noradrenaline level in the blood which could alleviate the depressant action of EGDN reinjection.
The clinical significance of these findings is discussed.
PMCID: PMC1009431  PMID: 5044604
4.  Work stress and recovery measured by urinary catecholamines and cortisol excretion in long distance coach drivers 
OBJECTIVES: To evaluate coach drivers' work stress during work and in the course of recovery from work by measurement of urinary catecholamines and cortisol. METHODS: The urinary excretion rate of adrenaline, noradrenaline, and cortisol of 10 coach drivers was studied during a long distance trip of three days and two consecutive days off. Each driver was asked to provide seven urine samples on the working days and six urine samples on the days off. The second day off was considered as the baseline. RESULTS: An occupationally induced disturbance of the circadian rhythmicity was found for adrenaline and noradrenaline but not for cortisol. The mean excretion rates of adrenaline on the first working day and most samples on all working days were higher than the baseline. For both adrenaline and noradrenaline the mean excretion rates on the first day off were lower than the baseline. For cortisol, the mean excretion rate on all working days was higher than the baseline. A trend towards accumulation of cortisol excretion from the first working day to the third working day was found. A backward shift in peak concentrations was found for adrenaline and noradrenaline on the second working day, as was a forward shift in peak concentration of cortisol on both days off. CONCLUSIONS: Long distance coach drivers showed occupationally induced reactivity in rates of urinary excretion of adrenaline, noradrenaline, and cortisol. After the outward journey the rates of excretion of catecholamines did not return to baseline values. The course of recovery in adrenaline excretion after the journey showed a new phenomenon, which has been called "fatigue debt". It is recommended that longer resting times in shuttle bus trips and fixed days off after these kind of trips should be planned. Extensive future research should be focused on the additional relations between fatigue debt and health complaints.
 
PMCID: PMC1757599  PMID: 9764101
5.  Nocturnal asthma and urinary adrenaline and noradrenaline excretion 
Thorax  1977;32(6):677-683.
Soutar, C. A., Carruthers, M., and Pickering, C. A. C. (1977).Thorax, 32, 677-683. Nocturnal asthma and urinary adrenaline and noradrenaline excretion. Urinary adrenaline and noradrenaline excretion, heart rate, and peak expiratory flow rate have been measured every two hours for 24 hours in seven asthmatic patients suffering from nocturnal or early morning exacerbations of dyspnoea. The excretions of these catecholamines were normal or slightly raised, this being consistent with a normal response to asthma or the conditions of the test.
The expected physiological fall in catecholamine excretion occurred at night. In every patient the peak expiratory flow rate fell to its lowest values during the period of lowest catecholamine excretion, and the mean two-hourly peak expiratory flow rate for all seven patients was significantly related to the sum of the mean adrenaline and noradrenaline excretion in each preceding two-hour period (p<0·05).
Individually, in three patients the relationship between peak expiratory flow rate and adrenaline and noradrenaline excretion during the evening and night was so close as to be consistent with the hypothesis that changes in sympathetic tone mediated the changes in asthma. In a further three patients the relationship was present but less clear, and in one the changes in peak flow rate and catecholamine excretion were dissociated.
Studies of mean heart rate and sinus arrhythmia gap suggested that an increase in vagal tone at night might have mediated the early morning asthma in the patient in whom changes in catecholamine excretion were dissociated from change in peak flow rate.
These findings would be consistent with the view that the physiological reduction in sympathetic tone at night mediates the nocturnal and early morning exacerbation of dyspnoea in some asthmatics, although other mechanisms such as alterations in vagal tone must be important in others. Confirmation of a causal relationship requires further study.
PMCID: PMC470812  PMID: 601729
6.  Interactions between Sympathomimetic Amines and Antidepressant Agents in Man 
British Medical Journal  1973;1(5849):311-315.
Intravenous infusions of phenylephrine, noradrenaline, adrenaline, and isoprenaline were given to healthy human volunteers after five to seven days on phenelzine, tranylcypromine, or imipramine, and cardiovascular responses were compared with those observed under control conditions. With monoamine oxidase inhibitors there was a 2-2½ fold potentiation of the pressor effect of phenylephrine, but no clinically significant potentiation of cardiovascular effects of noradrenaline, adrenaline, or isoprenaline. With imipramine there was potentiation of the pressor effects of phenylephrine (2-3 fold), noradrenaline (4-8 fold), and adrenaline (2-4 fold); there were dysrhythmias during adrenaline infusions, but no noticeable or consistent changes in response to isoprenaline.
Noradrenaline and adrenaline in amounts contained in local anaesthetics used in dentistry are not likely to be significantly potentiated in otherwise healthy patients receiving monoamine oxidase inhibitors. Hazardous potentiation of their cardiovascular effects might occur in patients receiving tricyclic antidepressants.
Our observations do not indicate that the hazards associated with isoprenaline inhalation by bronchial asthmatics would be increased by coincident therapy with a monoamine oxidase inhibitor or tricyclic antidepressant.
PMCID: PMC1588195  PMID: 4685619
7.  Predictors of Incident and Persistent Neck/Shoulder Pain in Iranian Workers: A Cohort Study 
PLoS ONE  2013;8(2):e57544.
Background
Pain in the neck and shoulder has been linked with various psychosocial risk factors, as well as with occupational physical activities. However, most studies to date have been cross-sectional, making it difficult to exclude reverse causation. Moreover, they have been carried out largely in northern Europe, and the relationship to psychosocial factors might be different in other cultural environments.
Methods
To explore causes of neck/shoulder pain, we carried out a longitudinal study in Iranian nurses and office workers. Participants (n  = 383) completed a baseline questionnaire about neck/shoulder pain in the past month and possible risk factors, and were again asked about pain 12 months later. Associations with pain at follow-up were explored by Poisson regression and summarised by prevalence rate ratios (PRRs).
Results
After adjustment for other risk factors, new pain at follow-up was more frequent in office workers than nurses (PRR 1.9, 95%CI 1.3–2.8), among those with worst mental health (PRR 1.8, 95%CI 1.0–3.0), in those who reported incentives from piecework or bonuses (PRR1.4, 95%CI 1.0–2.0), and in those reporting job dissatisfaction (PRR 1.5, 95%CI 1.0–2.1). The strongest predictor of pain persistence was somatising tendency.
Conclusions
Our findings are consistent with a hazard of neck/shoulder pain from prolonged use of computer keyboards, although it is possible that the association is modified by health beliefs and expectations. They also indicate that the association of low mood with neck/shoulder pain extends to non-European populations, and is not entirely attributable to reverse causation. Psychosocial aspects of work appeared to have relatively weak impact.
doi:10.1371/journal.pone.0057544
PMCID: PMC3585357  PMID: 23469019
8.  The metabolic and renal effects of adrenaline and milrinone in patients with myocardial dysfunction after coronary artery bypass grafting 
Critical Care  2007;11(2):R51.
Introduction
Myocardial dysfunction necessitating inotropic support is a typical complication after on-pump cardiac surgery. This prospective, randomized pilot study analyzes the metabolic and renal effects of the inotropes adrenaline and milrinone in patients needing inotropic support after coronary artery bypass grafting (CABG).
Methods
During an 18-month period, 251 patients were screened for low cardiac output upon intensive care unit (ICU) admission after elective, isolated CABG surgery. Patients presenting with a cardiac index (CI) of less than 2.2 liters/minute per square meter upon ICU admission – despite adequate mean arterial (titrated with noradrenaline or sodium nitroprusside) and filling pressures – were randomly assigned to 14-hour treatment with adrenaline (n = 7) or milrinone (n = 11) to achieve a CI of greater than 3.0 liters/minute per square meter. Twenty patients not needing inotropes served as controls. Hemodynamics, plasma lactate, pyruvate, glucose, acid-base status, insulin requirements, the urinary excretion of alpha-1-microglobuline, and creatinine clearance were determined during the treatment period, and cystatin-C levels were determined up to 48 hours after surgery (follow-up period).
Results
After two to four hours after ICU admission, the target CI was achieved in both intervention groups and maintained during the observation period. Plasma lactate, pyruvate, the lactate/pyruvate ratio, plasma glucose, and insulin doses were higher (p < 0.05) in the adrenaline-treated patients than during milrinone or control conditions. The urinary excretion of alpha-1-microglobuline was higher in the adrenaline than in the control group 6 to 14 hours after admission (p < 0.05). No between-group differences were observed in creatinine clearance, whereas plasma cystatin-C levels were significantly higher in the adrenaline than in the milrinone or the control group after 48 hours (p < 0.05).
Conclusion
This suggests that the use of adrenaline for the treatment of postoperative myocardial dysfunction – in contrast to treatment with the PDE-III inhibitor milrinone – is associated with unwarranted metabolic and renal effects.
Clinical trials registration: ClinicalTrials.gov NCT00446017.
doi:10.1186/cc5904
PMCID: PMC2206480  PMID: 17470271
9.  17-Ketosteroid and 17-hydroxycorticosteroid excretion in patients with duodenal ulceration 
Gut  1962;3(4):327-332.
The 24-hour excretion of 17-ketosteroids and 17-hydroxycorticosteroids has been estimated in a series of male duodenal ulcer subjects and compared with that of 56 normal male controls. It has been found that both 17-ketosteroid and 17-hydroxycorticosteroid excretion is less in ulcer subjects than in the control group; these differences are not large but in the case of 17-hydroxycorticosteroids they are statistically significant. For active ulcers (107 men) 17-hydroxycorticosteroid excretion is approximately 78% of normal and 17-ketosteroid excretion 93% of normal; in the quiescent phase (50 men) the differences are rather larger, being respectively 71% and 86% of normal. This reduced excretion persists after operation in both the short term, six months after operation (53 men), and the long term, 10 years and more after gastric resection (39 men).
PMCID: PMC1413375  PMID: 13950054
10.  Splanchnic and renal elimination and release of catecholamines in cirrhosis. Evidence of enhanced sympathetic nervous activity in patients with decompensated cirrhosis. 
Gut  1984;25(10):1034-1043.
Plasma noradrenaline (NA) and adrenaline (A) concentrations were determined in different vascular areas in 32 patients with cirrhosis and in nine controls during a right sided heart, liver, and renal vein catheterisation. The patients were divided into four groups: (I) Compensated (without ascites); (II) Recompensated on diuretic treatment because of former ascites; (III) Decompensated (with ascites) without treatment and (IV) Decompensated on diuretic treatment. Median arterial noradrenaline concentrations were 1.48, 1.07, 2.66, 4.14 and 2.50 nmol/l in controls, group I, II, III, and IV, respectively, the three last mentioned values being significantly raised (p less than 0.01). Median arterial adrenaline concentrations were not significantly increased. In patients arterial-hepatic venous extraction ratios of noradrenaline and adrenaline were on the average 25% (p less than 0.01) and 20% (p less than 0.02) less than those of the controls, indicating a slightly reduced splanchnic elimination of catecholamines in cirrhoses. In controls and group I significant renal venous-arterial noradrenaline differences were absent (0.00 and 0.03 nmol/l) while renal venous-arterial noradrenaline differences were significantly increased in groups II, III and IV (0.47, 0.53 and 0.68 nmol/l, p less than 0.01), indicating a significant net release of noradrenaline from the kidneys in recompensated and decompensated patients. Renal extraction of adrenaline was normal. In conclusion, increased arterial noradrenaline in decompensated and recompensated cirrhosis is only to a limited extent owing to reduced net splanchnic elimination. More likely the increase is caused by release of noradrenaline from the kidneys and possibly other organs indicating enhanced sympathetic nervous tone in these conditions.
PMCID: PMC1432557  PMID: 6479678
11.  Adrenaline modulates the global transcriptional profile of Salmonella revealing a role in the antimicrobial peptide and oxidative stress resistance responses 
BMC Genomics  2008;9:458.
Background
The successful interaction of bacterial pathogens with host tissues requires the sensing of specific chemical and physical cues. The human gut contains a huge number of neurons involved in the secretion and sensing of a class of neuroendocrine hormones called catecholamines. Recently, in Escherichia coli O157:H7, the catecholamines adrenaline and noradrenaline were shown to act synergistically with a bacterial quorum sensing molecule, autoinducer 3 (AI-3), to affect bacterial virulence and motility. We wished to investigate the impact of adrenaline on the biology of Salmonella spp.
Results
We have determined the effect of adrenaline on the transcriptome of the gut pathogen Salmonella enterica serovar Typhimurium. Addition of adrenaline led to an induction of key metal transport systems within 30 minutes of treatment. The oxidative stress responses employing manganese internalisation were also elicited. Cells lacking the key oxidative stress regulator OxyR showed reduced survival in the presence of adrenaline and complete restoration of growth upon addition of manganese. A significant reduction in the expression of the pmrHFIJKLM antimicrobial peptide resistance operon reduced the ability of Salmonella to survive polymyxin B following addition of adrenaline. Notably, both phenotypes were reversed by the addition of the β-adrenergic blocker propranolol. Our data suggest that the BasSR two component signal transduction system is the likely adrenaline sensor mediating the antimicrobial peptide response.
Conclusion
Salmonella are able to sense adrenaline and downregulate the antimicrobial peptide resistance pmr locus through the BasSR two component signalling system. Through iron transport, adrenaline may affect the oxidative stress balance of the cell requiring OxyR for normal growth. Both adrenaline effects can be inhibited by the addition of the β-adrenergic blocker propranolol. Adrenaline sensing may provide an environmental cue for the induction of the Salmonella stress response in anticipation of imminent host-derived oxidative stress. However, adrenaline may also serve in favour of the host defences by lowering antimicrobial peptide resistance and hence documenting for the first time such a function for a hormone.
doi:10.1186/1471-2164-9-458
PMCID: PMC2576261  PMID: 18837991
12.  STUDIES IN EDEMA  
1. Adrenalin injected intraperitoneally increases the rapidity of absorption of fluid from the peritoneal cavity, independently of whether the solution to be absorbed is hypotonic or hypertonic or is approximately isotonic with the blood serum. The intravenous injection of adrenalin also increases the absorption of fluid, but not so markedly as does the intraperitoneal injection. 2. Adrenalin injected either intraperitoneally or intravenously increases the quantity of sodium chloride absorbed. The relative absorption of sodium chloride—the movement from the peritoneal cavity of sodium chloride, as compared with the movement of water—is slightly increased when 0.85 per cent. of sodium chloride solution and adrenalin are injected intraperitoneally; but it is diminished when adrenalin is injected intravenously, or when 1.5 per cent. sodium chloride solution and adrenalin are injected. When distilled water has been injected intraperitoneally, adrenalin decreases the relative amount of sodium chloride in the peritoneal fluid—a fact that is evidently related to the increased elimination of sodium chloride through the kidneys under the influence of adrenalin. 3. When 0.85 per cent. sodium chloride solution is injected into the peritoneal cavity, the blood becomes diluted after two hours and a half. When adrenalin is also injected, the dilution of the blood is less marked, in spite of the increased absorption under the influence of adrenalin. When distilled water is injected into the peritoneal cavity, the blood is diluted equally in control and adrenalin experiments. When 1.5 per cent. sodium chloride solution is injected, the dilution of the blood is very slight, and in adrenalin experiments it is the same as in control experiments or very slightly greater than in control experiments. 4. The increase of absorption from the peritoneal cavity caused by the injection of adrenalin is not due to the increased diuresis caused by the injection of this substance. 5. The injection of adrenalin causes a temporary increase in the osmotic pressure of the blood, which gradually returns to normal. Under certain conditions, after the injection of adrenalin, there is a tendency toward maintaining the higher osmotic pressure of the blood serum, even up to the end of the experiment. We have reason to believe that this increase in the osmotic pressure of the blood is the main factor in increasing the absorption of fluid from the peritoneal cavity. 6. In experiments in which 0.85 per cent. sodium chloride solution has been injected intraperitoneally, either with or without adrenalin, there exists a tendency of the peritoneal fluid to attain a greater osmotic pressure than the blood serum, in spite of the fact that the injected fluid is slightly hypotonic as compared with the blood serum. We note a similar condition in cases of general edema in man, in which the osmotic pressure of the ascitic fluid is greater than that of the other edematous fluids, or even that of the blood serum. There exists, therefore, a mechanism that causes the passage of osmotically active substances from the blood or from the tissues into the peritoneal cavity, and that causes the osmotic pressure of the peritoneal fluid to become higher than that of the blood. It follows from our experiments that this mechanism, which causes the ascites in edematous persons to have such a high osmotic pressure, is not dependent upon certain pathological changes in the lining membranes or upon other pathological conditions, but exists already in normal animals. 7. The addition of 1.22 per cent. calcium chloride solution to 0.83 per cent. sodium chloride solution, in such proportions as we used in our infusion experiments, in which we determined the transudation into the peritoneal cavity, delays the absorption of fluid from the peritoneal cavity but very slightly. Therefore, calcium chloride increases directly the transudation into the peritoneal cavity and does not cause an increase in the amount of fluid in the peritoneal cavity merely by inhibiting the absorption. 8. It follows that adrenalin does not increase the amount of peritoneal transudate found after the intravenous infusion of large quantities of sodium chloride solution, to which adrenalin has been added, by delaying the absorption from the peritoneal cavity. The increased amounts of peritoneal fluid must be due to increased transudation into the peritoneal cavity; and the adrenalin, in view of its marked effect on absorption from the peritoneal cavity, must increase the movement of fluid into the peritoneal cavity much more strongly than could be assumed from the figures obtained in the infusion experiments.
PMCID: PMC2124791  PMID: 19867329
13.  Influence of cardiopulmonary bypass on water balance hormones in children 
British Heart Journal  1992;68(3):309-312.
Objective—To determine the changes in the endocrine mechanisms of fluid balance after cardiopulmonary bypass in children.
Design—Prospective study; analysis of numbered plasma samples performed blind with respect to clinical data.
Setting—Regional paediatric cardiothoracic unit.
Patients—Nine patients, median age 4, range 2 to 9 years, five males. Patients under the age of 1 year were excluded because of the frequent blood sampling involved.
Main outcome measures—Plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin, plasma renin activity, aldosterone, noradrenaline and adrenaline, and urinary concentrations of cyclic guanosine monophosphate (cGMP) as measured by radioimmunoassay.
Results—After 30 minutes of cardiopulmonary bypass plasma atrial natriuretic peptide (ANP) decreased from (mean (SEM)) 151 (71) pg/ml to 52 (44) pg/ml (NS), and urinary production of its second messenger cyclic guanosine monophosphate (cGMP) decreased from 1286 (600) pmol/ml to 151 (414) pmol (p < 0·05). Other plasma concentrations of hormones studied did not change significantly although arginine vasopressin, adrenaline, and noradrenaline increased whereas aldosterone and plasma renin activity decreased. After cardiopulmonary bypass stopped there was an immediate and significant rise in plasma ANP, but within the next 24 hours plasma ANP declined significantly (p < 0.05), decreasing from 294 (49) pg/ml to 64 (29) pg/ml at 22 hours. In the postoperative period there was a significant correlation between plasma ANP and both mean fluid balance (r = 0·96, p < 0·001) and mean urine output (r = 0·97, p < 0·001). Plasma aldosterone peaked (p < 0·05) at 22 hours after operation, and argine vasopressin peaked (p < 0·05) at two hours and then declined (p < 0·05) to a trough at 24 hours. Plasma renin activity, adrenaline, noradrenaline, and urinary cGMP concentrations, and mean central venous pressure did not change significantly in the postoperative period.
Conclusion—The changes documented show the differing pattern of release of water balance hormones invoked by cardiopulmonary bypass. The central role of ANP is shown by its strong correlation with urinary output and its similarly strong relation to fluid balance.
PMCID: PMC1025077  PMID: 1327039
14.  CATECHOLAMINES AND β2-ADRENOCEPTOR GENE EXPRESSION BEFORE AND AFTER MAXIMAL INCREMENTAL CYCLE TEST IN YOUNG ICE HOCKEY PLAYERS: RELATION TO WORK PERFORMED 
Biology of sport  2013;30(2):85-90.
The aim of this study was to assess the plasma adrenaline and noradrenaline concentrations as well as whole blood β2-adrenoceptor gene (ADRB2) expression in young ice hockey players before and immediately after exercise in relation to performed work. Nineteen Youth National Team ice hockey players were subjected to the maximal incremental cycloergometer exercise. The test was done in the pre-competitive phase of training. Among many parameters the plasma adrenaline and noradrenaline concentrations and ADRB2 gene expression in peripheral blood mononuclear cells (PBMC) were determined before and after exercise. The average performed work was 3261.3 ± 558.3 J · kg−1 and maximal oxygen consumption (VO2max) for all players was 53.85 ± 3.91 mL · kg−1 min−1. The geometric mean of the ADRB2 gene expression was statistically significantly different before and after exercise (P ≤ 0.05), while adrenaline and noradrenaline levels in plasma significantly increased after exercise. In the analysed group of athletes we found that initial level of plasma noradrenaline correlated with the performed work (r = - 0.55, P < 0.014) and normalized ADRB2 expression before the exercise correlated with the work done by them (r = 0.48, P<0.039). However, no statistically significant correlations were found between the plasma adrenaline or noradrenaline concentrations and ADRB2 gene expression in peripheral blood of the players. The performed work in the maximal incremental exercise test of regularly training young ice hockey players depends on the initial levels of noradrenaline in plasma and ADRB2 mRNA in PBMC.
doi:10.5604/20831862.1044222
PMCID: PMC3944583  PMID: 24744472
ice hockey players; catecholamines; ADRB2; maximal incremental cycle test
15.  Release of endogenous vasopressors during and after cardiopulmonary resuscitation. 
Heart  1996;75(2):145-150.
OBJECTIVE: To assess whether plasma endothelin, adrenaline, noradrenaline, arginine vasopressin, adrenocorticotropin, and cortisol concentrations were higher during cardiopulmonary resuscitation in patients in whom resuscitation was successful than in those in whom it failed, and to measure the concentrations of these hormones in the immediate post-resuscitation phase. DESIGN: Prospective, descriptive study. SETTING: Emergency medical service at a university hospital. PATIENTS: 60 patients with cardiac arrest out of hospital. INTERVENTIONS: Blood samples were drawn and blood pressure and heart rate were measured during cardiopulmonary resuscitation, before and after the first dose of adrenaline was given and at 5, 15, 30, and 60 minutes after the restoration of spontaneous circulation. Plasma hormone concentrations were measured by radio-immunoassays. RESULTS: 24 of the 60 patients were successfully resuscitated and admitted to hospital: 36 were not. During cardiopulmonary resuscitation before adrenaline was given, the plasma concentration of endothelin (mean (SEM)) in resuscitated and in not resuscitated patients was 4.3 (0.9) pg/ml and 5.5 (0.4) pg/ml respectively (NS), adrenaline was 14.1 (2.0) ng/ml and 25.3 (3.6) ng/ml (P < 0.01), noradrenaline was 5.0 (0.9 ng/ml) and 8.4 (1.1 ng/ml) (P < 0.05), arginine vasopressin was 193 (28) pg/ml and 70 (9) pg/ml (P < 0.001), adrenocorticotropin was 128 (34) pg/ml and 57 (6) pg/ml (P < 0.05), and cortisol was 18 (3) microgram/dl and 15 (2) microgram/dl (NS). During cardiopulmonary resuscitation after adrenaline was given endothelin in resuscitated and in not resuscitated patients was 4.0 (1.0) pg/ml and 5.3 (0.5) pg/ml (NS), adrenaline was 145 (16) ng/ml and 201 (21) ng/ml (P < 0.05), noradrenaline was 3.9 (0.9) ng/ml and 8.3 (1.1) ng/ml (P < 0.01), arginine vasopressin was 177 (27) pg/ml and 58 (9) pg/ml (P < 0.001), adrenocorticotropin was 234 (92) pg/ml and 85 (9) pg/ml (P < 0.001), and cortisol was 17 (2) microgram/dl and 13 (2) microgram/dl (NS). CONCLUSIONS: Despite a tremendous adrenosympathetic response, the lower arginine vasopressin and adrenocorticotropin concentrations during cardiopulmonary resuscitation in patients in whom resuscitation failed may influence vital organ perfusion and hence the success of resuscitation. Plasma concentrations of arginine vasopressin and adrenocorticotropin may have a more important effect on outcome than previously thought.
PMCID: PMC484250  PMID: 8673752
16.  Circadian rhythms in plasma concentration of 11-hydroxycorticosteroids in men working on night shift and in permanent night workers 
Conroy, R. T. W. L., Elliott, Ann L., and Mills, J. N. (1970).Brit. J. industr. Med.,27, 170-174. Circadian rhythms in plasma concentration of 11-hydroxycorticosteroids in men working on night shift and in permanent night workers. Blood samples have been collected for estimation of plasma 11-hydroxycorticosteroids from three groups of workers - day and night shift workers in a light engineering factory, and night workers in a newspaper printing works. Up to five samples were collected over 24 hr, or two samples per 24 hr were collected for three days. In conformity with the observations of others, day workers showed maximal concentrations in the morning around the time when they started work. In the newspaper workers maximal concentrations were found when they awoke around 14·00 hr. Night shift workers in the engineering works showed a greater variety of pattern, some showing the pattern usual in a day worker, some showing a maximum concentration about midnight and a minimum around 06·00 hr and a large proportion showing no clear circadian rhythm.
In the newspaper workers the rhythm was thus well adapted to their pattern of nocturnal work, whereas relatively few of the night shift workers in the engineering works showed such adaptation. It appears that the adrenal cortical rhythm can be adapted to night work in a community in which this is universal, accepted and lifelong, but that such adjustment is unusual in men on night shift work for limited periods, and whose associates are mainly following a usual nycthemeral existence.
PMCID: PMC1009093  PMID: 5428635
17.  Renal function impairment induced by change in posture in patients with cirrhosis and ascites. 
Gut  1985;26(6):629-635.
The assumption of upright posture by patients with liver cirrhosis leads to striking activation of adrenergic and renin-angiotensin systems. The tilting-induced modifications in renal function of eight healthy controls and 14 untreated patients with liver cirrhosis and ascites were related to plasma concentrations of noradrenaline, renin activity and aldosterone. All patients had preserved renal blood perfusion. All parameters were evaluated during bed rest for two hours and in the sitting posture for one hour. Basal plasma renin activity (0.1 greater than p greater than 0.05), aldosterone and noradrenaline concentrations (p less than or equal to 0.01) were raised in cirrhotics. The renal function tests (creatinine clearance, filtered sodium, tubular rejection fraction, urinary sodium excretion) were significantly reduced in cirrhosis. Under basal conditions, in cirrhotic patients tubular rejection fraction and urinary sodium excretion were inversely related to both noradrenaline and aldosterone concentrations. After tilting, the noradrenaline and aldosterone integrated outputs (sigma delta) were significantly greater in cirrhosis. All renal function tests significantly decreased in cirrhotics, whereas creatinine clearance only significantly decreased in controls. Patient's tubular rejection fraction of sodium and sodium excretion were related to sigma delta aldosteronaemia (r = -0.72; p less than 0.01), but no longer to sigma delta plasma noradrenaline.
PMCID: PMC1432759  PMID: 3891534
18.  EXPERIMENTS ON THE GLOMERULAR DISTRIBUTION OF BLOOD IN THE MAMMALIAN KIDNEY 
The results of thirteen control experiments, designed to show the number of glomeruli in the rabbit's kidney open to the circulation under the chosen experimental conditions without intentional interference, indicate the "normal" range to be from 42 to 100 per cent. Since ten of the thirteen results fall within the figures 56 and 89 per cent, we may take these figures as the chief basis for our discussion. Three experiments only were made in which renal vasodilatation was produced by caffeine and salt. The percentage of open glomeruli found was in every case higher than any control except one. The results show without ambiguity that in rabbits, as in frogs, renal vasodilatation by caffeine is accompanied by increase in number of patent glomeruli. Our prime interest lay in the general question rather than in the action of individual substances in the group of vasodilators; hence this series was not extended further. Among the experiments designed to test the effects of renal vasoconstriction are to be found nine in which adrenalin was injected, two in which CO2 was inhaled, two in which the splanchnic nerve was stimulated, and four in which hemorrhage was induced. Not all are of equal value for our present purpose, inasmuch as the degree of certainty with which we can assume that renal vasoconstriction was actually produced is not the same in all. Enough experience with the action of adrenalin on the kidney of the anesthetized rabbit is available to permit the assertion that the dosages used in the nine adrenalin experiments were sufficient to insure constriction of renal vessels. Similar certainty exists in the experiment in which high concentration of CO2 was used; less in the case of 10 per cent CO2. Stimulation of the splanchnic nerve in rabbits so frequently fails to produce results typical of direct constriction of renal vessels that we may regard the production of this effect in the two experiments in which this was done as doubtful. In the perfusion experiments by Richards and Plant (7) the reactions of the renal vessels to stimulation of the splanchnic nerve resembled those to intravenously injected adrenalin rather than to the direct excitation of constrictor fibers. In six rabbits in which Livingston subjected the nerve to varying degrees of electrical stimulation, in one only was distinct constriction of the renal vessels produced, and in this a latent period of 45 seconds occurred between the beginning of stimulation and the production of effect. In one of our experiments a rabbit was used in which the superior cervical sympathetic ganglion on the left side had been extirpated months before. During the stimulation of the splanchnic nerve the left pupil was observed to dilate, showing increased adrenalin secretion. Hence, we are inclined to regard the two attempts to produce vasoconstriction by this means as having been largely unsuccessful. In one experiment only of the four in which hemorrhage was induced was there unmistakable evidence of compensatory vasoconstriction which may have involved the renal vessels. The blood pressure curve of this animal showed rhythmically occurring waves of the Traube-Hering type and dyspnea was noted. In this the estimate of open glomeruli was 28 per cent. In the other three experiments no such change occurred and no dyspnea was seen. In pithed frogs, hemorrhage alone of moderate extent is less apt to lessen the number of patent glomeruli than are any of the other constrictor agencies tried by Richards and Schmidt. In this discussion, therefore, we lay little weight on the results obtained in the two experiments in which the splanchnic nerve was stimulated and on those of the first three hemorrhage experiments. The chief conclusion to be drawn from these experiments is that which was anticipated from the observations of Richards and Schmidt on frogs, and of Khanolkar on rabbits; viz., that in the rabbit, renal vasodilatation and renal vasoconstriction are usually associated with increase and decrease respectively in number of glomeruli through which blood flows (see Text-fig. 1). Analogous changes apparently occur in the capillary pathway in individual glomeruli. Hence renal function in mammals may be altered by changes in the extent of glomerular filtration surface to which the blood has access. Other conditions remaining the same, it is obvious that changes in extent of filtration surface must result in proportionate changes in urinary output. The figures for rate of urine elimination at the time of injection of the dye in these experiments are in substantial agreement with these statements (see Text-fig. 2). Exceptions to our chief conclusion as stated have been encountered. In Experiment 57,86 per cent of the glomeruli were open in a constricted kidney which was excreting no urine: in Experiment 30, 16 per cent were open in the kidney which was eliminating seven drops per minute: the outputs of the kidneys in the caffeine experiments were far higher than those of control kidneys in which comparable numbers of glomeruli were open. In considering these exceptions, account must be taken of the fact that other conditions do not commonly remain constant. When a renal vasodilator is introduced we conceive not only of possible increase in extent of accessible glomerular surface, but also of increase in glomerular pressure and increased rate of renewal of fluid in contact with glomerular membranes. Hence the response is greater than can be accounted for by any one factor alone. A basis of experiment exists in support of the belief that usually sufficient differences in physiological state exist among the small arteries and arterioles of the kidney so that a constrictor influence, exerted equally upon all, elicits various degrees of response (1). Closure of some, continuing patency of others, results. Blood flow and blood pressure in the glomeruli which are supplied by the vessels which remain open may be decreased, increased, or unchanged according See PDF for Structure. to the relation between the degree of reaction in those vessels and the height of arterial blood pressure. It is not to be expected that urinary outputs will uniformly vary with the number of glomeruli remaining open. Rapid blood flow and high glomerular pressure in relatively few glomeruli may result in more urine than slow flow and low pressure in many. This argument is implicit in Hermann's original statement and is completely in harmony with the result of direct observation in the frog. It is supported by the data of Experiment 30. In Experiment 57, however, urine was suppressed by adrenalin when 86 per cent of the glomeruli remained open. The kidney in this experiment was highly diuretic before the adrenalin injection. We may, therefore, assume that all or nearly all of the glomeruli were open and that intermittent contractions of the arterioles were minimal; hence, that the physiological state of the vessels concerned was more nearly uniform than is conceived to be the case when only a fraction of the glomeruli are open and in which intermittent contractions and relaxations must be pronounced. Thus a relatively uniform constriction was produced in all of such degree as to lessen materially glomerular pressure and blood flow, but insufficient to actually close more than a few afferent arterioles. In Experiment 33, the dosage of adrenalin was such as to permit the possibility that constrictor action may have been largely confined to efferent vessels (8). While the exceptional results have been discussed at greater length than has been devoted to the majority of experiments, we believe that they do not constitute adequate ground for criticism of the chief conclusion as stated.
PMCID: PMC2131062  PMID: 19869079
19.  The celiac ganglion modulates LH-induced inhibition of androstenedione release in late pregnant rat ovaries 
Background
Although the control of ovarian production of steroid hormones is mainly of endocrine nature, there is increasing evidence that the nervous system also influences ovarian steroidogenic output. The purpose of this work was to study whether the celiac ganglion modulates, via the superior ovarian nerve, the anti-steroidogenic effect of LH in the rat ovary. Using mid- and late-pregnant rats, we set up to study: 1) the influence of the noradrenergic stimulation of the celiac ganglion on the ovarian production of the luteotropic hormone androstenedione; 2) the modulatory effect of noradrenaline at the celiac ganglion on the anti-steroidogenic effect of LH in the ovary; and 3) the involvement of catecholaminergic neurotransmitters released in the ovary upon the combination of noradrenergic stimulation of the celiac ganglion and LH treatment of the ovary.
Methods
The ex vivo celiac ganglion-superior ovarian nerve-ovary integrated system was used. This model allows studying in vitro how direct neural connections from the celiac ganglion regulate ovarian steroidogenic output. The system was incubated in buffer solution with the ganglion and the ovary located in different compartments and linked by the superior ovarian nerve. Three experiments were designed with the addition of: 1) noradrenaline in the ganglion compartment; 2) LH in the ovarian compartment; and 3) noradrenaline and LH in the ganglion and ovarian compartments, respectively. Rats of 15, 19, 20 and 21 days of pregnancy were used, and, as an end point, the concentration of the luteotropic hormone androstenedione was measured in the ovarian compartment by RIA at various times of incubation. For some of the experimental paradigms the concentration of various catecholamines (dihydroxyphenylalanine, dopamine, noradrenaline and adrenaline) was also measured in the ovarian compartment by HPLC.
Results
The most relevant result concerning the action of noradrenaline in the celiac ganglion was found on day 21 of pregnancy resulting in the inhibition of androstenedione release from the ovarian compartment. In addition on day 15 of pregnancy, LH placed in the ovarian compartment led to an inhibition of the release of androstenedione, and this inhibitory effect was further reinforced by the joint action of noradrenaline in the celiac ganglion and LH in the ovary. The levels of catecholamines in the ovarian compartment showed differences among the experiments; of significance, the joint treatment of noradrenaline in the celiac ganglion and LH in the ovary resulted in a remarkable increase in the ovarian levels of noradrenaline and adrenaline when compared to the effect achieved by either one of the compounds added alone.
Conclusion
Our results demonstrate that the noradrenergic stimulation of the celiac ganglion reinforces the LH-induced inhibition of androstenedione production by the ovary of late pregnant rats, and that this effect is associated with marked changes in the release of catecholamines in the ovary.
doi:10.1186/1477-7827-4-66
PMCID: PMC1769501  PMID: 17184551
20.  Behavioral stress accelerates prostate cancer development in mice 
Prostate cancer patients have increased levels of stress and anxiety. Conversely, men who take beta blockers, which interfere with signaling from the stress hormones adrenaline and noradrenaline, have a lower incidence of prostate cancer; however, the mechanisms underlying stress–prostate cancer interactions are unknown. Here, we report that stress promotes prostate carcinogenesis in mice in an adrenaline-dependent manner. Behavioral stress inhibited apoptosis and delayed prostate tumor involution both in phosphatase and tensin homolog–deficient (PTEN-deficient) prostate cancer xenografts treated with PI3K inhibitor and in prostate tumors of mice with prostate-restricted expression of c-MYC (Hi-Myc mice) subjected to androgen ablation therapy with bicalutamide. Additionally, stress accelerated prostate cancer development in Hi-Myc mice. The effects of stress were prevented by treatment with the selective β2-adrenergic receptor (ADRB2) antagonist ICI118,551 or by inducible expression of PKA inhibitor (PKI) or of BCL2-associated death promoter (BAD) with a mutated PKA phosphorylation site (BADS112A) in xenograft tumors. Effects of stress were also blocked in Hi-Myc mice expressing phosphorylation-deficient BAD (BAD3SA). These results demonstrate interactions between prostate tumors and the psychosocial environment mediated by activation of an adrenaline/ADRB2/PKA/BAD antiapoptotic signaling pathway. Our findings could be used to identify prostate cancer patients who could benefit from stress reduction or from pharmacological inhibition of stress-induced signaling.
doi:10.1172/JCI63324
PMCID: PMC3561807  PMID: 23348742
21.  Do biomarkers of stress mediate the relation between socioeconomic status and health? 
Objectives
To test the relation between socioeconomic status (SES) and biomarkers of chronic stress, including basal cortisol, and to test whether these biomarkers account for the relation between SES and health outcomes.
Design
Cross sectional study using data from the 2000 social and environmental biomarkers of aging study (SEBAS).
Setting
Taiwan.
Participants
Nationally representative sample of 972 men and women aged 54 and older.
Main outcome measures
Highest risk quartiles for 13 biomarkers representing functioning of the neuroendocrine system, immune/inflammatory systems, and the cardiovascular system: cortisol, adrenaline (epinephrine), noradrenaline (norepinephrine), serum dihydroepiandrosterone sulphate (DHEA‐S), insulin‐like growth factor 1 (IGF1), interleukin 6 (IL6), albumin, systolic blood pressure, diastolic blood pressure, waist‐hip ratio, total cholesterol‐HDL ratio, HDL cholesterol, and glycosylated haemoglobin; self reported health status (1–5) and self reported mobility difficulties (0–6).
Results
Lower SES men have greater odds of falling into the highest risk quartile for only 2 of 13 biomarkers, and show a lower risk for 3 of the 13 biomarkers, with no association between SES and cortisol. Lower SES women have a higher risk for many of the cardiovascular risk factors, but a lower risk for increased basal readings of adrenaline, noradrenaline, and cortisol. Inclusion of all 13 biological markers does not explain the relation between SES and health outcomes in the sample.
Conclusions
These data do not support the hypothesis that chronic stress, via sustained activation of stress related autonomic and neuroendocrine responses, is an important mediator in the relation between SES and health outcomes. Most notably, lower SES is not associated with higher basal levels of cortisol in either men or women. These results place an increased burden of proof on researchers who assert that psychosocial stress is an important pathway linking SES and health.
doi:10.1136/jech.2005.040816
PMCID: PMC2566242  PMID: 16790837
socioeconomic status; stress; cortisol; inequalities in health; Taiwan
22.  Urinary excretion of free noradrenaline and adrenaline in trained and untrained men. 
Measurements of free noradrenaline and adrenaline were made in the urine of 28 men sampled after rest and exercise prior to, and following six and twelve weeks of an excercise programme. The training consisted of thirty minutes of running and walking four times per week at an intensity estimated at 75% of the age-predicted maximum heart rate. A fifteen minute standardized cycle ergometer work test was conducted on all subjects prior to the training and following six and twelve weeks of training. Noradrenaline and adrenaline excretions in the urine were measured before and after the work test.
PMCID: PMC1859503  PMID: 884438
23.  Nicotine stimulates pancreatic cancer xenografts by systemic increase in stress neurotransmitters and suppression of the inhibitory neurotransmitter γ-aminobutyric acid 
Carcinogenesis  2009;30(3):506-511.
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer mortality in Western countries. We have shown previously that four representative human PDAC cell lines were regulated by beta-adrenoreceptors via cyclic adenosine 3′,5′-monophosphate (cAMP)-dependent signaling. In the current study, we have tested the hypothesis that nicotine stimulates the growth of PDAC xenografts in nude mice by increasing the systemic levels of the stress neurotransmitters adrenaline and noradrenaline, which are the physiological agonists for beta-adrenoreceptors and that inhibition by γ-aminobutyric acid (GABA) of the adenylyl cyclase-dependent pathway downstream of adrenoreceptors blocks this effect. The size of xenografts from PDAC cell line Panc-1 was determined 30 days after inoculation of the cancer cells. Stress neurotransmitters in serum as well as cAMP in the cellular fraction of blood and in tumor tissue were assessed by immunoassays. Levels of GABA, its synthesizing enzymes GAD65 and GAD67 and beta-adrenergic signaling proteins in the tumor tissue were determined by western blotting. Nicotine significantly increased the systemic levels of adrenaline, noradrenaline and cAMP while increasing xenograft size and protein levels of cAMP, cyclic AMP response element-binding protein and p-extracellular signal-regulated kinase 1/2 in the tumor tissue. Nicotine additionally reduced the protein levels of both GAD isozymes and GABA in tumor tissue. Treatment with GABA abolished these responses to nicotine and blocked the development of xenografts in mice not exposed to nicotine. These findings suggest that the development and progression of PDAC is subject to significant modulation by stimulatory stress neurotransmitters and inhibitory GABA and that treatment with GABA may be useful for marker-guided cancer intervention of PDAC.
doi:10.1093/carcin/bgp010
PMCID: PMC2722153  PMID: 19131543
24.  Randomised controlled trial evaluating effects of morphine on plasma adrenaline/noradrenaline concentrations in newborns 
Objectives: To determine the effects of continuous morphine infusion in ventilated newborns on plasma concentrations of adrenaline (epinephrine) and noradrenaline (norepinephrine) and their relation to clinical outcome.
Design: Blinded, randomised, placebo controlled trial.
Setting: Level III neonatal intensive care units in two centres.
Patients: A total of 126 ventilated neonates (inclusion criteria: postnatal age <3 days, duration of ventilation <8 hours, indwelling arterial catheter for clinical purposes; exclusion criteria: severe asphyxia, severe intraventricular haemorrhage, major congenital anomalies, neuromuscular blockers).
Interventions: Plasma adrenaline and noradrenaline concentrations were determined in patients during blinded morphine (n = 60) and placebo (n = 66) infusion (100 µg/kg plus 10 µg/kg/h).
Results: Plasma concentrations at baseline (nmol/l with interquartile range in parentheses) were comparable in infants treated with morphine (adrenaline, 0.22 (0.31); noradrenaline, 2.52 (2.99)) or placebo (adrenaline, 0.29 (0.46); noradrenaline, 2.44 (3.14)). During infusion, median adrenaline concentrations were 0.12 (0.28) and 0.18 (0.35) and median noradrenaline concentrations were 2.8 (3.7) and 3.8 (4.0) for the morphine and placebo treated infants respectively. Multivariate analyses showed that noradrenaline (p = 0.029), but not adrenaline (p = 0.18), concentrations were significantly lower in the morphine group than the placebo group. Furthermore, noradrenaline concentrations were related to the length of stay in the neonatal intensive care unit.
Conclusions: Continuous morphine infusion significantly decreased plasma noradrenaline concentrations in ventilated newborns compared with placebo treatment. The results of this study support the idea that routine morphine administration decreases stress responses in ventilated neonates.
doi:10.1136/adc.2003.046425
PMCID: PMC1721820  PMID: 15613571
25.  Polychlorinated biphenyl exposure and effects in transformer repair workers. 
Fifty-five present and past transformer repair workers exposed to polychlorinated biphenyls (PCBs) and 56 unexposed comparison workers were evaluated in a clinical-epidemiologic study. The groups were similar in most demographic variables. Adipose tissue lipid and serum PCBs concentrations were higher in current exposed workers (geometric means adipose 2.1 ppm, serum 12.2 ppb). Concentrations in comparison (0.6 ppm and 4.6 ppb) and previously exposed (0.83 ppm and 5.9 ppb) workers were lower. Statistically significant differences in serum albumin and lactic dehydrogenase, but not in other liver function tests, were seen between the exposed and comparison groups; however, after adjustment for confounding variables, no correlations were observed between liver function tests and either adipose or serum PCBs concentrations. Statistically significant correlation both before and after adjustment for confounding variables were seen with adipose PCBs and 24-hr urinary 17-hydroxycorticosteroid excretion and with serum PCBs and serum gamma-glutamyl transpeptidase. Both associations could reflect microsomal enzyme induction among other possibilities. No differences were seen in fasting serum triglycerides, total cholesterol, LDL, HDL or VLDL cholesterol between the two exposure groups. A statistically significant correlation between serum PCBs and serum triglycerides, total cholesterol, and VLDL cholesterol was removed by adjusting for confounding variables. No correlation was seen between adipose PCBs concentrations and any serum lipid component. Partition phenomena could account for these findings.(ABSTRACT TRUNCATED AT 250 WORDS)
PMCID: PMC1568555  PMID: 2863134

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