Plasma free and sulfate conjugated catecholamine levels during acute physiological stimulation in man

The responses of plasma free and sulfate-conjugated catecholamines to acute physiological stimulation was examined in normal male subjects. Catecholamines were measured with a sensitive radioenzymatic assay incorporating simultaneous hydrolysis of sulfate conjugates and O-methylation of free norepinephrine and epinephrine. Following 20 minutes recumbency after venepuncture 30 +/- 3% of norepinephrine and 16 +/- 5% of epinephrine was in thr free form. Free catecholamines generally increased during standing, cold immersion and isometric handgrip, but sulfates did not change. Bicycle ergometry markedly increased free catecholamines which rapidly returned to basal levels at the end of exercise. In contrast, sulfated norepinephrine decreased substantially with exercise in all subjects but returned to basal levels 3 minutes after stopping exercise. Epinephrine sulfate varied considerably between subjects but showed a similar, although smaller, fall with exercise. Thus, during physiological stimulation, which caused increases in free norepinephrine and epinephrine levels in plasma, the only consistent change in sulfated catecholamines was a marked fall in norepinephrine sulfate after bicycle exercise. This may indicate saturation of sulfotransferase activity, substrate inhibition or impaired tissue conjugation.     

Plasma free and sulfoconjugated catecholamine responses to varying exercise intensity

Plasma free catecholamines rise during exercise, but sulfoconjugated catecholamines reportedly fall. This study examined the relationship between exercise intensity and circulating levels of sulfoconjugated norepinephrine, epinephrine, and dopamine. Seven exercise-trained men biked at approximately 30, 60, and 90% of their individual maximal oxygen consumption (VO2max) for 8 min. The 90% VO2max period resulted in significantly increased plasma free norepinephrine (rest, 219 +/- 85; exercise, 2,738 +/- 1,149 pg/ml; P less than or equal to 0.01) and epinephrine (rest, 49 +/- 49; exercise, 555 +/- 516 pg/ml; P less than or equal to 0.05). These changes were accompanied by consistent increases in sulfoconjugated norepinephrine at both the 60% (rest, 852 +/- 292; exercise, 1,431 +/- 639; P less than or equal to 0.05) and 90% (rest, 859 +/- 311; exercise, 2,223 +/- 1,015; P less than or equal to 0.05) VO2max periods. Plasma sulfoconjugated epinephrine and dopamine displayed erratic changes at the three exercise intensities. These findings suggest that sulfoconjugated norepinephrine rises during high-intensity exercise.     

Exercise training and the stress response in rainbow trout, Salmo gairdneri Richardson

Plasma levels of catecholamines, cortisol, and glucose were monitored in rainbow trout during a 6-week forced swimming exercise programme. Compared to resting non-exercised controls, resting trained fish had lower levels of epinephrine, norephinephrine, cortisol, and glucose during the last 3 weeks of training. Initially, trained fish that were swimming had higher levels of epinephrine than resting trained fish. After 2 weeks of exercise, swimming did not significantly elevate epinephrine levels in trained fish. Glucose levels were consistently greater in swimming fish than in resting fish. At the end of the training period, exercised trout had lower (15–20%) oxygen consumption rates while resting or swimming than unexercised fish.
After a 5-month forced swimming exercise programme plasma levels of catecholamines and glucose were monitored in trained and untrained cannulated rainbow trout after 2 min of mild agitation. Trained fish showed an immediate (within 1 min) increase in the levels of epinephrine, but not norepinephrine and a delayed (within 15 min) increase in the levels of plasma glucose. Epinephrine levels returned to pre-stress levels within 15 min. Untrained fish had no significant increase in the plasma levels of norepinephrine, epinephrine, or glucose.     

Adrenergic versus VIPergic control of cyclic AMP in human colonic crypts

The actions of catecholamines on VIP-induced cyclic AMP is studied in human colon. We show that: (1) Epinephrine in the 10(-7)-10(-3) M concentration range (ED50 = 11.10(-6) M) inhibits VIP-induced cyclic AMP rise in isolated colonic epithelial cells; the maximal inhibition reaches 30% of VIP effect; epinephrine alters the efficacy of the peptide and does not modify its potency; epinephrine also reduces the basal cyclic AMP level. (2) The inhibition is found with other alpha adrenergic agonists with the order of potencies epinephrine greater than norepinephrine greater than phenylephrine. Clonidine has a poor intrinsic activity but antagonizes the action of epinephrine. (3) The inhibition of VIP action by epinephrine is reversed by the alpha antagonists dihydroergotamine, phentolamine and the alpha 2 antagonist yohimbine, while unaffected by the beta antagonist propranolol and the alpha 1 antagonist prazosin, (4) Epinephrine inhibits VIP-stimulated adenylate cyclase activity in preparations of colonic plasma membranes. Thus catecholamines exert through an alpha 2 adrenoreceptor a negative control on basal and VIP-stimulated cyclic AMP formation in human colon. We suggest that colonic cyclic AMP metabolism undergoes a dual control: VIPergic, activator and adrenergic, inhibitor.     

Cardiovascular and adrenal medullo-sympathetic reactions to acute tobacco poisoning

We studied the effects after cigarette quicksmoking in 15 subjects on plasma catecholamines levels (epinephrine and norepinephrine), on heart rate and arterial pressure. Smoking-associated increments in mean plasma norepinephrine and epinephrine as well as in heart rate and arterial pressure were demonstrated. The lack of correlation between the increase of the adrenergic system activity and this of the hemodynamic parameters can be explained by their own different characteristics.     

Assay of catecholamines in human plasma: Studies of a single isotope radioenzymatic procedure

The sensitive specific radioenzymatic procedure for determination of catecholamines originally described from our laboratory by Coyle and Henry (1) has been optimized for use in assay of human plasma levels of dopamine, norepinephrine and epinephrine. Dopamine and the total of norepinephrine and epinephrine are assayed by 0-methylation while norepinephrine is determined by N-methylation. Epinephrine is calculated from the difference between the 0-methylation and N-methylation procedures. In a group of 13 normal subjects, plasma levels of epinephrine were found to be 67 ± 9.2 pg/ml, norepinephrine 208 ± 16.9 pg/ml and dopamine 33 ± 8.1 pg/ml. Dopamine determinations are of low reliability because of relatively high blanks and necessary corrections.     

Metabolic and temperature responses to physical exercise in thyroidectomized dogs.

The purpose of the present work was to further elucidate the role of thyroid hormones in the control of body temperature and metabolism during physical exercise. Changes in rectal temperature (Tre), some parameters of exercise-metabolism and in the plasma noradrenaline (NA) levels were examined in eight dogs performing submaximal treadmill exercise to exhaustion before and after thyroidectomy (THY). The metabolic 'responses to adrenaline (A) infusion were also compared in intact and THY dogs. During the exercise performed by THY dogs Tre increases were markedly attenuated, plasma FFA level increases were reduced and the pattern of plasma NA changes was modified in comparison with control runs. The reduced exercise-induced FFA mobilization in THY dogs might be attributed to a lower activation of the adrenergic system in the later stage of exercise and to the weaker lipolytic action of catecholamines. The attenuated Tre increases during exercise performed by THY dogs and the exercise-hyperthermia described previously in dogs treated with thyroid ormones suggest that an optimum level of thyroid hormones is necessary to induce typical changes in body temperature during physical exercise.     

Sympathoadrenal response to repetitive exercise in normal and asthmatic subjects

To explore the role of catecholamine release in the pathogenesis of exercise-induced asthma, we had seven asthmatic and seven normal subjects undergo three hourly exercise challenges that were matched for inspired air temperature, minute ventilation, and relative work loads. Pulmonary mechanics and plasma epinephrine and norepinephrine were measured before, at end exercise, and serially after each challenge. There were no differences in the pattern of sympathoadrenal response of asthmatic and normal subjects, and both groups released sufficient quantities of epinephrine and norepinephrine into the peripheral circulation to allow these compounds to function as circulating hormones. As the catecholamines rose with repetitive exercise, progressive bronchodilation occurred in the asthmatics at the end of the work load, thus decreasing the apparent magnitude of the obstructive response. In addition to their effects on airway smooth muscle, the alpha-adrenergic actions of both catecholamines may have reduced airway wall hyperemia and edema. These data demonstrate that asthmatics do not have a defect in catecholamine release during exercise and that the physiological expression of exercise-induced asthma can be modulated by the sympathoadrenal epiphenomena that are associated with physical exertion.     

Influence of cold exposure on blood lactate response during incremental exercise

This study examined the effect of acute exposure of the whole body to cold on blood lactate response during incremental exercise. Eight subjects were tested with a cycle ergometer in a climatic chamber, room temperature being controlled either at 24 degrees C (MT) or at -2 degrees C (CT). The protocol consisted of a step increment in exercise intensity of 30 W every 2 min until exhaustion. Oxygen consumption (VO2) was measured at rest and during the last minute of each exercise intensity. Blood samples were collected at rest and at exhaustion for estimations of plasma norepinephrine (NE), epinephrine (E), free fatty acid (FFA) and glucose concentrations, during the last 15 s of each exercise step and also during the 1st, 4th, 7th, and the 10th min following exercise for the determination of blood lactate (LA) concentration. The VO2 was higher during CT than during MT at rest and during nearly every exercise intensity. At CT, lactate anaerobic threshold (LAT), determined from a marked increase of LA above resting level, increased significantly by 49% expressed as absolute VO2, and 27% expressed as exercise intensity as compared with MT. The LA tended to be higher for light exercise intensities and lower for heavy exercise intensities during CT than during MT. The E and NE concentrations increased during exercise, regardless of ambient temperature. Furthermore, at rest and at exhaustion E concentrations did not differ between both conditions, while NE concentrations were greater during CT than during MT. Moreover, an increase off FFA was found only during CT.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hormonal responses to exercise during moderate cold exposure in young vs. middle-age subjects.

The influence of moderate cold exposure on the hormonal responses of atrial natriuretic factor (ANF), arginine vasopressin (AVP), catecholamines, and plasma renin activity (PRA) after exhaustive exercise was studied in 9 young and 10 middle-aged subjects. Exercise tests were randomly performed in temperate (30 degrees C) and cold (10 degrees C) environments. Heart rate, oxygen consumption, and peripheral arterial blood pressure were measured at regular intervals. Blood samples were collected before and immediately after exercise at 30 or 10 degrees C. Plasma sodium and potassium concentrations as well as hemoglobin and hematocrit were measured, and the change in plasma volume was calculated. At rest and during exercise, oxygen consumption was similar during exposure to both temperate and cold temperatures. During submaximal exercise intensities, the rise in heart rate was blunted while the increase in systolic blood pressure was significantly greater at 10 than at 30 degrees C. The increases in plasma sodium and potassium concentrations after exhaustion were similar between environments, as was the decrease in plasma volume. In both groups, all plasma hormones were significantly elevated postexercise, with the AVP response similar at 10 and 30 degrees C. However, the norepinephrine and ANF responses were significantly greater while the PRA response was significantly reduced at 10 degrees C. In the middle-aged subjects the epinephrine response to exercise was higher at 10 than at 30 degrees C. The greater ANF and reduced PRA responses to exercise in the cold may have resulted from central hemodynamic changes caused by cold-induced cutaneous vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Skeletal muscle metabolic and ionic adaptations during intense exercise following sprint training in humans.

The effects of sprint training on muscle metabolism and ion regulation during intense exercise remain controversial. We employed a rigorous methodological approach, contrasting these responses during exercise to exhaustion and during identical work before and after training. Seven untrained men undertook 7 wk of sprint training. Subjects cycled to exhaustion at 130% pretraining peak oxygen uptake before (PreExh) and after training (PostExh), as well as performing another posttraining test identical to PreExh (PostMatch). Biopsies were taken at rest and immediately postexercise. After training in PostMatch, muscle and plasma lactate (Lac(-)) and H(+) concentrations, anaerobic ATP production rate, glycogen and ATP degradation, IMP accumulation, and peak plasma K(+) and norepinephrine concentrations were reduced (P<0.05). In PostExh, time to exhaustion was 21% greater than PreExh (P<0.001); however, muscle Lac(-) accumulation was unchanged; muscle H(+) concentration, ATP degradation, IMP accumulation, and anaerobic ATP production rate were reduced; and plasma Lac(-), norepinephrine, and H(+) concentrations were higher (P<0.05). Sprint training resulted in reduced anaerobic ATP generation during intense exercise, suggesting that aerobic metabolism was enhanced, which may allow increased time to fatigue.     

Effects of exercise on plasma catecholamine levels in the toad, Bufo paracnemis: role of the adrenals and neural control

Resting plasma epinephrine (E) and norepinephrine (N) concentrations for intact toads (Bufo paracnemis) were 5.57+/-1.0 and 0.88+/-0.38 ng/ml, respectively. Exercise induced a significant increase in heart rate, blood pressure and plasma epinephrine (about 4.3 times), whereas norepinephrine remained unchanged. The resting [E]/[N] ratio was 6.3 and increased to 32.9 during exercise. Adrenal denervation did not alter the basal plasma catecholamine or norepinephrine levels after exercise, but prevented the increase in epinephrine during exercise, suggesting that in the intact toad this increase is due to adrenal secretion whereas resting norepinephrine may be liberated by extra-adrenal chromaffin tissues. This also suggests that the adrenal glands can release selectively the two catecholamines. The increases in heart rate and blood pressure in denervated toads were not significantly different from those of intact animals, suggesting that during exercise the sympathetic nerves play the main role in inducing cardiovascular responses. Spinal transection induced a significant increase in basal norepinephrine levels, which remained elevated after exercise. Since spinal toads are unable to perform spontaneous movements it is possible that this increase may be caused by this stressful condition. The increases in heart rate and blood pressure observed in spinal toads during exercise may be due to direct mechanical effects of venous return on the heart.     

Role of the sympathoadrenal system in the regulation of glycogen metabolism in resting and exercising skeletal muscles.

The purpose of the present study was to characterize the role of catecholamines in the regulation of skeletal muscle glycogen metabolism during exercise. Using the rat hindlimb perfusion technique we have measured skeletal muscle glycogen content, glycogen phosphorylase and synthase activities in sympathectomized and/or demedullated rats under epinephrine treatment (10(-7) M) at rest and during muscle contraction. When epinephrine and/or norepinephrine deficiency was induced, muscle contraction resulted in a decrease in glycogen content (-63%) despite a decrease in glycogen phosphorylase activity ratio (0.25 to 0.11; p less than 0.001) and an increase in glycogen synthase activity ratio (0.13 to 0.27; p less than 0.001). Under these conditions, epinephrine treatment further reduced glycogen content while blunting the changes in the activity ratio of the rate-limiting enzymes. These data indicate that catecholamines do not play a primary role in skeletal muscle glycogen breakdown during acute exercise and suggest that allosteric regulators may be of prime importance.     

A reduction in the hyperventilation threshold by intravenous infusion of adrenaline in the treadmill exercise

Seven healthy male subjects underwent a treadmill incremental work test in control conditions and during an intravenous epinephrine infusion (10 micrograms/min). At all exercise intensities, epinephrine increased heart rate, ventilation, respiratory quotient and plasma lactate levels without significant changes in oxygen consumption. Under epinephrine infusion, the "anaerobic threshold", considered as the critical intensity at which ventilation began to increase non linearly with oxygen consumption, appeared at a lower intensity and for a higher plasma lactate level than in control conditions. We conclude that the hyperventilation threshold does not necessarily reflect a muscular hypoxia. It could be due to an effect of catecholamines on peripheral chemoreceptors, maybe by alpha-adrenergic vasoconstriction in the carotid bodies.     

A single bout of exercise induces beta-adrenergic desensitization in human adipose tissue

This study was designed to assess whether physiological activation of the sympathetic nervous system induced by exercise changes adipose tissue responsiveness to catecholamines in humans. Lipid mobilization in abdominal subcutaneous adipose tissue was studied with the use of a microdialysis method in 11 nontrained men (age: 22. 3 +/- 1.5 yr; body mass index: 23.0 +/- 1.6). Adipose tissue adrenergic sensitivity was explored with norepinephrine, dobutamine (beta(1)-agonist), or terbutaline (beta(2)-agonist) perfused during 30 min through probes before and after 60-min exercise (50% of the maximal aerobic power). The increase in extracellular glycerol concentration during infusion was significantly lower after the exercise when compared with the increase observed before the exercise (P < 0.05, P < 0.02, and P < 0.01, respectively, for norepinephrine, dobutamine, and terbutaline). In a control experiment realized without exercise, no difference in norepinephrine-induced glycerol increase between the two infusions was observed. To assess the involvement of catecholamines in the blunted beta-adrenergic-induced lipolytic response after exercise, adipose tissue adrenergic sensitivity was explored with two 60-min infusions of norepinephrine or epinephrine separated by a 60-min interval. With both catecholamines, the increase in glycerol was significantly lower during the second infusion (P < 0.05). The findings suggest that aerobic exercise, which increased adrenergic activity, induces a desensitization in beta(1)- and beta(2)-adrenergic lipolytic pathways in human subcutaneous adipose tissue.     

Effect of submaximal muscular exercise of short duration on urinary excretion of catecholamines, DOPA and their metabolites]

Thirteen human subjects were submitted to a moderate muscular work on ergometric bicycle (at intensity corresponding to 80% of maximal oxygen uptake during 10 min). No modifications were observed in the urinary amounts of the three catecholamines (A, NA, DA), DOPA, DOPAC and 3-MT. On the contrary, the excretion of metadrenaline (MN) and normetadrenaline (NMN) was slightly increased, showing a mild stimulation of adrenergic system. Our result point out the interest of urinary methoxyamines as useful index of adrenergic activity in man. For experimental and physiopathological use, the metabolic alteration induced by a short submaximal muscular work is negligible for most adrenergic compounds, except for MN and NMN, the amounts of which are slightly modified.     

Leukocytosis of exercise: role of cardiac output and catecholamines

The effect of propranolol (5 mg iv) on the leukocytosis of exercise was studied in seven normal young males. Leukocyte counts, plasma norepinephrine (NE), epinephrine (E), and cardiac output were measured at rest and in the steady state of several submaximal work loads when subjects exercised on a cycle ergometer. The results in control experiments were compared with those obtained on a different day with propranolol. Propranolol decreased heart rate at all work loads (P less than 0.001) but had no effect on the increase in cardiac output at increasing work loads. Plasma NE and E levels were similar at rest and in exercise in control and propranolol studies. There was no effect of propranolol on the increase in leukocyte counts with increasing work loads. Although propranolol did not affect the increase in total leukocyte count, the increase in lymphocyte count at higher work loads was less with propranolol. We conclude that the demargination of leukocytes from the pulmonary circulation in exercise is probably a mechanical effect of the increase in cardiac output. However, we have not excluded a contribution from a humoral event that would decrease the adherence of leukocytes to endothelium during exercise. The smaller increase in lymphocytes at higher work loads in the presence of propranolol suggests that catecholamines affect the lymphocyte count over and above their effect on cardiac output.     

Influence of cold, exercise, and caffeine on catecholamines and metabolism in men

Recently we found that caffeine ingestion did not enhance either thermal or fat metabolic responses to resting in cold air, despite an increase in plasma epinephrine and free fatty acids. Theophylline, another methylxanthine, has been shown to be effective during exercise but not at rest during cold stress. Therefore we hypothesized that caffeine ingestion before exercise in cold air would have a thermal-metabolic impact by increasing fat metabolism and increasing oxygen consumption. Young adult men (n = 6) who did not normally have caffeine in their diet performed four double-blind trials. Thirty minutes after ingesting placebo (dextrose, 5 mg/kg) or caffeine (5 mg/kg) they either exercised (60 W) or rested for 2 h in 5 degrees C air. Cold increased (P less than 0.05) plasma norepinephrine while both caffeine and exercise increased (P less than 0.05) epinephrine. Serum free fatty acids and glycerol were increased, but there were no differences between rest and exercise or placebo and caffeine. Caffeine had no influence on either respiratory exchange ratio or oxygen consumption either at rest or during exercise. The exercise trials did not significantly warm the body, and they resulted in higher plasma norepinephrine concentrations and lower mean skin temperatures for the first 30 min. The data suggest that skin temperature stimulates plasma norepinephrine while caffeine has little effect. In contrast, caffeine and exercise stimulate plasma epinephrine while cold has minimal effect. Within the limits of this study caffeine gave no thermal or metabolic advantage during a cold stress.     

Effect of exercise on epinephrine turnover in trained and untrained male subjects

The kinetics underlying plasma epinephrine concentrations were studied. Six athletes (T) and six sedentary males (C) were given intravenous infusions of 3H-labeled epinephrine, after which arterial blood was drawn. They rested sitting and bicycled continuously to exhaustion (60 min at 125 W, 60 min at 160 W, 40 min at 200 W, and 240 W to the end). Work time was 154 +/- 13 (SE) (T) and 75 +/- 6 (C) min. At rest, epinephrine clearance was identical [28.4 +/- 1.3 (T) vs. 29.2 +/- 1.8 (C) ml . kg-1 . min-1], but plasma concentration [1.42 +/- 0.27 (T) vs. 0.71 +/- 0.16 (C) nmol . l-1] and, accordingly, secretion [2.9 +/- 0.7 vs. 1.5 +/- 0.4 nmol . min-1] were higher (P less than 0.05) in T than C subjects. Epinephrine clearance was closely related to relative work load, decreasing from 15% above the basal level at 30% of maximal O2 uptake (VO2 max) to 22% below at 76% of VO2 max. Epinephrine concentrations increased much more with work intensity than could be accounted for by changes in clearance and were, at exhaustion, higher (P less than 0.05) in T (7.2 +/- 1.6) than in C (2.5 +/- 0.7 nmol . l-1) subjects despite similar glucose, heart rate, and hematocrit values. At a given load, epinephrine clearance rapidly became constant, whereas concentration increased continuously. Forearm extraction of epinephrine invalidated use of blood from a cubital vein or a hand vein arterialized by hot water in turnover measurements. During exercise, changes in epinephrine concentrations reflect changes in secretion rather than in clearance. Training may increase adrenal medullary secretory capacity.     

Plasma catecholamine and lactate response during graded exercise with varied glycogen conditions.

The relationships between the lactate threshold (TLa), plasma catecholamines, and ventilatory threshold (TVE) were examined under normal and glycogen-depleted conditions. Nine male subjects performed a graded exercise test on a bicycle ergometer in a normal glycogen (NG) state and in a glycogen-depleted (GD) state to determine if manipulation of muscle glycogen content would affect their ventilatory, lactate, and catecholamine responses. High correlations were found between plasma lactate and the two catecholamines, epinephrine (r = 0.964) and norepinephrine (r = 0.965) under both conditions. The GD protocol resulted in a shift in the TLa to a later work rate; inflections in epinephrine and norepinephrine shifted in a coordinated manner. TVE and TLa occurred at similar work loads under NG conditions [67.2 +/- 1.5 and 65.6 +/- 2.3% maximal oxygen consumption (VO2max), respectively], but TLa occurred at a later work load (75.3 +/- 1.9% VO2max) compared with TVE (68.3 +/- 1.6% VO2max) under GD conditions. These results suggest a causal relationship between plasma lactate and epinephrine during a graded exercise test under the glycogen conditions studied. Although an association existed between ventilation and lactate, this relationship was not as strong.