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The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been shown to modulate various physiological and psychological functions such as fatigue. Altered regulation of the serotonergic system has been suggested to play a role in response to exercise stress. In the present study, the influence was investigated of acute endurance exercise and short-term increase in the amount of training on the concentrations of the 5-HT precursor tryptophan (TRP), of prolactin (PRL) and of branched-chain amino acids (BCAA) in the blood, as well as on the binding of [3H]ketanserin to the serotonin-2A (5-HT2A) receptors on platelets. Nine healthy endurance-trained men were tested the day before (I) and after (II) a 9-day training programme. Samples of venous blood were drawn after an overnight fast and following 5 h of cycling. Fasted and post-exercise plasma concentrations of free TRP, BCAA and free TRP:BCAA ratio did not differ between I and II. A significant decrease of plasma BCAA (P < 0.01) and significant augmentations of plasma free TRP, free TRP:BCAA ratio and PRL (P < 0.01) were found post-exercise. The increase in plasma PRL was smaller in II compared with I. Acute endurance exercise reduced the density of platelet 5-HT2A receptor [3H]ketanserin binding sites at I and II (P < 0.05). The basal density of the binding sites and the affinity of [3H]ketanserin for these binding sites were unaffected by an increase in the amount of training. The present results support the hypothesis that acute endurance exercise may increase 5-HT availability. This was reflected in the periphery by increased concentration of the 5-HT precursor free TRP, by increased plasma PRL concentration, and by a reduction of 5-HT2A receptors on platelets. It remains to be resolved whether these alterations in the periphery occur in parallel with an increase in the availability of 5-HT in the brain.

The aim of this study was to investigate hypothalamic-pituitary-adrenal (HPAA) and -gonadal (HPGA) axis responses to post-exercise (30 min at 65% VO2max) combined corticotrophin, luteinizing hormone and thyrotrophin releasing hormone challenge (0.7 microg/ kg body mass) in elderly distance runners (DR; age: 68.9+/-4.2 year) and sedentary individuals (SI; age: 69.1+/-2.6 year). Plasma cortisol, growth hormone, prolactin, luteinizing hormone, follicle stimulating hormone and total testosterone (T) concentrations pre- and post-exercise as well as in response to stimulation did not differ between DR and SI. Plasma adrenocorticotropic hormone returned to pre-exercise level in DR 60 min and in SI 90 min post-stimulation. Free T was lower in DR at all time points. Our results do not support the notion of altered releasing hormone-stimulable HPAA and HPGA synthesis-secretion capacity in elderly males after endurance training.

We investigated the response of plasma and platelet:free catecholamine ([CA]) and sulphated catecholamine ([CA-S]) concentrations after an incremental treadmill test to exhaustion and during recovery. In triathletes (n = 9) plasma and platelet [CA] and [CA-S] were measured before, immediately after and 0.5 and 24 h after exercise. In long-distance runners (n = 9) and in controls (n = 10) plasma [CA] and [CA-S] were determined 2 h instead of 24 h after exercise. Platelet [CA] and [CA-S] remained unchanged throughout the study. Plasma [CA] increased after exercise in all groups (P < 0.05) and returned to pre-exercise values within 0.5 h of recovery. Plasma sulphoconjugated noradrenaline concentration ([NA-S]) was elevated after exercise in the triathletes, long-distance runners and in controls [9.96 (SEM 0.84) nmol.l-1, 11.8 (SEM 1.19) nmol.l-1, 9.53 (SEM 1.10) nmol.l-1, respectively; P < 0.05] compared with resting values [7.13 (SEM 1.04) nmol.l-1, 6.19 (SEM 0.56) nmol.l-1, 6.76 (SEM 0.67) nmol.l-1, respectively] and remained elevated after 0.5 h of recovery [9.94 (SEM 1.14) nmol.l-1, 10.96 (SEM 0.80) nmol.l-1, 8.95 (SEM 0.99) nmol.l-1, respectively; P < 0.05]. In the long-distance runners and controls plasma [NA-S] remained elevated during 2 h of recovery [9.96 (SEM 0.76) nmol.l-1, 9.03 (SEM 0.88) nmol.l-1, respectively]. These results would indicate that plasma [NA-S] increases after sympathetic nervous system activation by an exhausting incremental exercise test and remain elevated up to 2 h after exercise.

Leucocyte cell counts and the phagocytic and chemotactic activities of neutrophil granulocytes were investigated in highly endurance-trained long-distance runners (n = 10) and triathletes (n = 10) during a moderate training period and compared with untrained subjects (n = 10) before and up to 24 h after a graded exercise to exhaustion on a treadmill. After exercise a leucocytosis was noted with a significant increase in lymphocyte (P < or = 0.01) and neutrophil (P < or = 0.01) counts in all groups. In neutrophils the number of ingested inert latex beads was significantly increased (P < or = 0.01) from 0.21 (SD 0.09) to 0.45 (SD 0.22) in controls, from 0.20 (SD 0.12) to 0.56 (SD 0.16) in long-distance runners and from 0.25 (SD 0.08) to 1.03 (SD 0.42) particles per cell in triathletes 24 h after exercise, compared with resting values. The capability of neutrophils to produce microbicidal reactive oxygen species fell (P < or = 0.05) immediately after exercise in all subjects and then increased by 36 (SD 8)%, 31 (SD 6)% and 19 (SD 9)% in controls, runners and triathletes respectively up to 24 h after exercise (P < or = 0.05) compared with pre-start values. With respect to the absolute number of neutrophils, ingestion capacity, production of superoxide anions and chemotactic activity, no significant differences were found between athletes and control subjects at rest and after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Despite the vasoconstrictory influence of the alpha-adrenergic system on the peripheral blood circulation the results of the sympathectomy were not satisfying in the therapy of peripheral arterial occlusive disease (PAOD). The aim of the present investigation was to clarify the pathophysiologic mechanisms of this clinical observation. Free and sulfoconjugated catecholamines were determined in the femoral artery, vein, and cubital vein of 19 healthy controls, 21 non-diabetic patients with PAOD stage II, 8 non-diabetic (PAOD IV) and 20 diabetic patients (D IV) with PAOD stage IV. In comparison with controls and group PAOD II an increased sympathoneuronal tone in group PAOD IV was evident at rest. Sympathetic activation was not restricted to the affected limb, since femoral and cubital venous norepinephrine levels were not different and plasma epinephrine fractional extraction (PEFE) was not altered by angiopathy. The lower sympathoneuronal activation in the group D IV may be attributed to an impaired pain perception or a reduced dopamine beta-hydroxylase activity indicated by a lower ratio of norepinephrine to dopamine. The failing long-term efficacy of lumbar sympathectomy in critical arterial limb disease may be explained by marked spontaneous sympathicolysis in diabetics, whereas in non-diabetics with sympathetic activation other mechanisms like development of unilateral Mönckeberg sclerosis, progression of proximal arterial occlusion or induction of steal effects have to be discussed.

Twenty healthy athletes performed a heavy physical exercise before and after a controlled training period of 3 months. As a result of physical training there was a reduction in lactate concentration during and after exercise. Plasma free fatty acids and triglyceride levels were lower at rest as well as during and after exercise. Insulin concentrations decreased during exercise before the training period whereas they remained constant afterwards. The composition of individual free fatty acids changed in the same way during exercise before and after training: fatty acids with shorter hydrocarbon chains increased, those with longer chains decreased. Comparing the pattern of individual free fatty acids before and after training a higher percentage of saturated and a lower percentage of mono-unsaturated fatty acids was observed. It is concluded that changes in the plasma free fatty acid profile during heavy exercise reflect a preferential uptake and oxidation of certain individual free fatty acids. The significance of training-induced changes in the plasma free fatty acid pattern is discussed.

Recently in vitro evidence has been presented that sulfonylurea derivatives exert their chronic extrapancreatic effect by increasing the number of cellular insulin receptors. To ascertain if this receptor effect holds in vivo, we performed a randomized double-blind study on 21 type I (0.3 ng/ml residual C-peptide secretory capacity after glucose/glibenclamide stimulation), and on 19 insulin treated type II (2.0 ng/ml C-peptide) diabetics. The patients received for six weeks 10 mg/d of glibenclamide in addition to insulin. Insulin binding was initially lower in type II (4.7 +/- 0.75% per 10(7) monocytes and 6.39 +/- 1.08% per 4.5 X 10(9) erythrocytes) than in type I diabetic patients (5.1 +/- 0.48% and 7.95 +/- 0.88% respectively) and in 12 normal subjects (5.25 +/- 0.48 and 8.1 +/- 0.94% respectively). Glibenclamide normalized the number of monocyte receptors (from 4.14 to 5.49 X 10(4) sites/cell) in type II patients, but was without effect in type I diabetics. Blood glucose was significantly reduced (240 to 182 mg/dl; p = 0.02) in the type II group with a concomitant decrease in glycosylated hemoglobin from 12.4 to 10.5% (p = 0.01). Most of the effect occurred during the first week of treatment. Glibenclamide was the more effective the worse the initial metabolic state (r = -0.93; p = 0.001). Erythrocyte insulin receptors decreased markedly in both groups, perhaps due to a sulfonyl urea-induced change in erythrocyte plasma survival time. It is concluded that sulfonylurea treatment is a valuable adjunct in reducing the insulin resistance in insulin treated type II diabetics. The effect depends on the availability of endogenous insulin, thus exhibiting only partly extrapancreatic character.(ABSTRACT TRUNCATED AT 250 WORDS)

The metabolites pyruvate, alanine and urea were determined under resting conditions in blood from the femoral artery, femoral vein and cubital vein of 23 patients with stage II, 10 patients and 20 diabetics with stage IV PAOD as well as 19 healthy volunteers. Measurements were also carried out immediately and 20 min after ergometric calf exercise in the patients with stage II PAOD and the controls. In both patient groups with stage IV PAOD, there were lower arterial and venous alanine levels and higher urea concentrations at rest than in patients with adequate resting circulation, which is evidence for increased hepatic alanine extraction. After exercise, a significantly higher increase in the arteriovenous difference of pyruvate concentration was to be found in the patient group with stage II PAOD than in the control group. Moreover, there was a significant increase in femoral venous concentration and a rise in the arteriovenous difference of alanine, indicating muscular release, only in the PAOD patients and not in the volunteers in spite of a three times higher exercise load. The exercise-induced rise in femoral venous alanine correlated closely with those of pyruvate and ammonia. Alanine formation fulfills the function of a non-toxic carrier of muscularly produced amino groups and represents in PAOD a compensating mechanism that delays the limitation of muscular contractility. Alanine determination, especially in association with an exercise test, appears to be suitable for assessing the extent of anaerobic energy production in muscles of limbs affected by PAOD.

The behaviour of muscular metabolism was investigated in 10 patients with peripheral arterial occlusive disease stage II at rest and after maximum ergometric calf exercise. The intracellular concentrations of phosphocreatine, inorganic phosphate and adenosine triphosphate as well as muscle pH were measured by means of 31P magnetic resonance spectroscopy and compared with those from a control group. In addition, arteriovenous differences in concentrations of lactate, pyruvate, ammonia, hypoxanthine and alanine in the femoral blood were determined. The fall in intracellular phosphocreatine concentration during exercise was significantly greater in the calf muscles of patients with arterial occlusion than in controls and correlated linearly with the increase in femoral arteriovenous differences in lactate, ammonia and alanine. A significant fall in intracellular pH occurred during muscular activity only in the patient group, but not in the identically exercised control group. The fall in pH correlated closely with the rise in arteriovenous lactate difference in the femoral blood. The intramuscular ATP concentration remained constant throughout the exercise procedure. The behaviour of both the directly and indirectly measured metabolites permits the deduction of activation of the creatine kinase reaction, glycolysis, myokinase reaction and the purine nucleotide cycle during exercise-induced hypoxia in the presence of arterial occlusive disease. The anaerobic production of energy is sufficient to maintain the ATP concentration even during claudication pain.(ABSTRACT TRUNCATED AT 250 WORDS)

In an earlier publication, we described a modified procedure for the determination of plasma catecholamine levels using high-performance liquid chromatography (HPLC), followed by amperometry. In this paper, we present our results on the variability of normal catecholamine values in plasma for noradrenaline (NA), adrenaline (A) and dopamine (DA). In 122 women and men at rest, the range for NA was 0.15-3.5 nmol/l, for A 0.01-0.8 nmol/l and for DA 0.04-4.5 nmol/l. We also describe the effects of orthostasis, intravenous catheters, food intake, cigarette smoking, age and sex on venous catecholamine levels. The efficiency of the HPLC method allowed us to check, using a large subject group, the results obtained by other authors from studies involving smaller subject groups with more expensive and time-consuming methods.

Cardiopulmonary and metabolic variables were investigated at maximal and submaximal bicycle ergometer exercises in 41 swimmers of both sexes, 8--18 years old. VO2 max and VO2 max . HR-1 were higher in boys than in girls and increased with maturity, while VO2 max. kg-1 and HVE were not influenced by this. The HV increased clearly during this growth period, the pubertal and postpubertal subjects showing 16 and 17% higher values for HV and HV . kg-1 than those reported in normal schoolchildren populations. During the submaximal exercise at 70% VO2 max the highest HR values were found in the prepubertal group, whilst the lowest were observed in the postpubertal subjects. These findings suggest that a given percentage of VO2 max as a reference unit, is more reliable than a certain HR to obtain comparable results in subjects with different ages. Blood samples were collected before, during, and after the submaximal exercise. Blood glucose and FFA did not differ in relation to the stages of maturity. During exercise, insulin decreased in prepubertal children, did not alter in pubertal adolescents, and increased in postpubertal subjects. The lactate concentration, during exercise, increased in relation to maturity. The same results were found for HGH, but no differences were found with regard to sex. Since the pattern of HGH secretion during exercise is similar to that found after arginine and insulin administration it is assumed that the same mechanism (i.e., sex hormones) triggers the HGH release.

The binding properties of 3- and 4-O-sulfo-conjugated dopamine (DA-3-O-S, DA-4-O-S) as well as 3-O-methylated dopamine (MT) to rat striatal dopamine D2 receptors were investigated. 3H-spiperone was used as a radioligand in the binding studies. In saturation binding experiments (+)butaclamol, which has been reported to bind to dopaminergic D2 and serotoninergic 5HT2 receptors, was used in conjunction with ketanserin and sulpiride, which preferentially label 5HT2 and D2 receptors, respectively, in order to discriminate between 3H-spiperone binding to D2 and to 5HT2 receptors. Under our particular membrane preparation and assay conditions, 3H-spiperone binds to D2 and 5HT2 receptors with a maximal binding capacity (Bmax) of 340 fmol/mg protein in proportions of about 75%:25% with similar dissociation constants KD (35 pmol/l; 43 pmol/l). This result was verified by the biphasic competition curve of ketanserin, which revealed about 20% high (KD = 24 nmol/l) and 80% low (KD = 420 nmol/l) affinity binding sites corresponding to 5HT2 and D2 receptors, respectively. Therefore, all further competition experiments at a tracer concentration of 50 pmol/l were performed in the presence of 0.1 mumol/l ketanserin to mask the 5HT2 receptors. DA competition curves were best fitted assuming two binding sites, with high (KH = 0.12 mumol/l) and low (KL = 18 mumol/l) affinity, present in a ratio of 3:1. The high affinity binding sites were interconvertible by 100 mumol/l guanyl-5-yl imidodiphosphate [Gpp(NH)p], resulting in a homogenous affinity state of DA receptors (KD = 2.8 mumol/l).2+ off

A study was undertaken to evaluate and to examine the role of substrate supply in 50 healthy subjects after long distance events, such as 10 km, 25 km, and marathon races. The metabolic, variables of carbohydrate metabolism were greatest in 10-km runners, with the highest increase in glucose, lactate, and pyruvate, while in marathon runners only moderate changes were observed. Marathon competitors gave the greatest decrease in insulin concentration whereas glucagon and cortisol showed a contrary tendency. As for lipid concentrations, the most remarkable point was that after the marathon competition the best runners had the highest increase in free fatty acids; the longer the race, the higher were the beta-hydroxybutyrate and acetoacetate levels after the competition. It is important to emphasize that the limiting factor up to 90 min duration is the competitor's ability to deplete the stores of glycogen. Beyond 90 min (or 25 km) the decrease in insulin, the rise in cortisol and the higher concentration of ketnne bodies found indicate a change in metabnlic response.

The effects of different physical training regimes on the plasma catecholamine values at rest and the density and responsiveness of adrenergic receptors at rest were investigated. The changes during well-defined training periods of swimmers, long-distance runners, weight lifters and wrestlers were compared with untrained male volunteers. The training of swimmers and long-distance runners, building up endurance, resulted in a significantly lower basal plasma norepinephrine (NE) concentration and a significantly or possibly lower ratio NE:EPI (epinephrine). Both values indicated reduced sympathetic activity and resulted also in a significantly lower beta-receptor density and a higher alpha 2-receptor sensitivity compared with the other groups investigated. However, swimming-specific characteristics provoked labile hypertensive blood pressure regulation with an unchanged heart rate in swimmers. Static training of weight lifters, building up power, also led to a lower NE concentration compared with untrained subjects, whereas beta-receptor density was unchanged and alpha 2-receptor density and sensitivity were decreased. Elevated blood pressure values were observed in weight lifters and swimmers due to a reduced baroreceptor sensitivity. The dynamic training of wrestlers affected only basal heart rate and alpha 2-receptor sensitivity, both of which were decreased. Different kinds of physical training caused various adaptations of the basal activity of the autonomic nervous system in which adrenergic receptors also became adapted. In this context, the stronger adrenergic circulatory component of overall sympathetic activity at rest in swimmers and long-distance runners resulted in lower beta-receptor density, and the reduced noradrenergic component sensitized alpha 2-receptors.

The concentrations of lactate, ammonia and hypoxanthine were determined in blood from the femoral artery, femoral vein and cubital vein under resting conditions in 23 patients with stage II, 10 patients and 20 diabetics with stage IV peripheral arterial occlusive disease (PAOD) and in 19 healthy subjects. The metabolite concentrations were also measured immediately and 20 min after calf exercise in the patients with stage II PAOD and in the controls. At rest, there was a negative arteriovenous difference in femoral lactate level and a positive arteriovenous difference in the ammonia level in all groups. After exercise to the claudication limit, the femoral venous concentration and arteriovenous difference for lactate increased in the patient group significantly higher than in the controls, who were exercised three times as heavily. Furthermore, there was a significant rise in femoral venous ammonia concentration with inversion of the arteriovenous difference into the negative range and an increase in femoral venous hypoxanthine concentration only in the patients with PAOD and not in the controls. A significant correlation was found between the exercise-induced increases in lactate and ammonia. The results indicate activation of the purine nucleotide cycle in the muscles of limbs with impaired circulation, even for a short duration of load. This can be explained by activation of the AMP-deaminase in type I and type IIa muscle fibres by anoxaemia. The purine nucleotide cycle has an emergency metabolic function in ischaemia to maintain muscle contractility. Ammonia determination in femoral blood permits, in association with lactate and hypoxanthine determination, a precise quantitative assessment of the metabolic effects of PAOD.(ABSTRACT TRUNCATED AT 250 WORDS)