Contribution of liver nerves,glucagon, and adrenaline to the glycaemic response to exercise in rats

The contribution of hepatic sympathetic innervation, glucagon and adrenaline to the glycaemic response to exercise was investigated in rats. Hepatically denervated (LDX) or sham operated (SHAM) rats with permanent catheters were therefore submitted to swimming with or without infusion of somatostatin in combination with adrenodemedul–lation. Blood samples were taken for measurements of blood glucose, plasma free fatty acids (FFA), adrenaline (A), noradrenaline (NA), insulin and glucagon. Liver denervation by itself did not influence glucose levels during exercise. Infusion of somatostatin in SHAM animals, which inhibited the exercise–induced glucagon response, led to enhanced sympathoadrenal outflow (measured as plasma A and NA) and a reduced blood glucose during exercise, suggesting that glucagon serves as a powerful mediator of the glycaemic response during swimming. Infusion of somatostatin in LDX animals failed to enhance plasma NA levels and led to a more pronounced reduction in blood glucose levels. This indicates that liver nerves do contribute to the glycaemic response to exercise when glucagon secretion is suppressed. Reduced blood glucose levels after adrenodemedullation revealed that adrenal A is another important mediator of the glucose response to exercise. Infusion of somatostatin in adreno–demedullated SHAM or LDX animals was not accompanied with increased NA outflow, suggesting that adrenal A is necessary to allow the compensatory increased outflow of NA from sympathetic nerves. In conclusion, the study shows that pancreatic glucagon and adrenal A are the predominant factors influencing the glycaemic response to exercise, whereas a role of the sympathetic liver nerves becomes evident when glucagon secretion is suppressed.     

The effect of water temperature on the hormonal response to prolonged swimming.

The relationship between thermoreception, hormonal secretion and muscular activity was studied. 6 men swam 60 min in 21, 27 and 33 degrees C water at a speed requiring 68% of VO2 max (determined in 27 degrees C water). Rectal temperature increased in 33 degrees C (1.3 +/- 0.2 degrees C, mean and S.E.) and 27 degrees C (0.7+/- 0.1 degrees C) expts. but decreased in 21 degrees C expts. (0.8 +/- 0.3 degrees C). Changes in esophageal and muscle temperatures parallelled changes in rectal temperature. Plasma noradrenaline was higher in 33 degrees C than in 27 degrees C expts. and growth hormone, cortisol and glucagon concentrations increased in 27 degrees C and 33 degrees C expts. only. Insulin concentrations were uniformly depressed during swimming at the different water temperatures. In 21 degrees C expts. noradrenaline and adrenaline concentrations were higher than in 27 degrees C expts. VO2, carbohydrate combustion and peak lactate were slightly lower in 33 degrees C expts. Plasma glucose decreased slightly and FFA and glycerol concentrations increased identically in all expts. Heart rate increased continuously during swimming in 27 degrees C and 33 degrees C expts., but not in 21 degrees C expts. In conclusion the rise in body temperatures normally observed during exercise enhances the exercise induced increases in the plasma concentrations of noradrenaline, cortisol, growth hormone and glucagon. Decreased body temperatures may elicit catecholamine secretion as a direct consequence of thermoreception. Shivering may account for previously observed decreases in insulin secretion during cold stress but not for increases in cortisol and growth hormone.     

The effect of water temperature on the hormonal response to prolonged swimming

The relationship between thermoreception, hormonal secretion and muscular activity was studied. 6 men swam 60 min in 21, 27 and 33°C water at a speed requiring 68 % of Vo_a max (determined in 27°C water). Rectal temperature increased in 33°C (1.3 ± 0.2°C, mean and S.E.) and 27°C (0.7 ± 0.1°C) expts. but decreased in 21°C expts. (0.8 ± 0.3°C). Changes in esophageal and muscle temperatures parallelled changes in rectal temperature. Plasma noradrenaline was higher in 33°C than in 27°C expts. and growth hormone, Cortisol and glucagon concentrations increased in 27°C and 33°C expts. only. Insulin concentrations were uniformly depressed during swimming at the different water temperatures. In 21°C expts. noradrenaline and adrenaline concentrations were higher than in 27°C expts. V_O2, carbohydrate combustion and peak lactate were slightly lower in 33°C expts. Plasma glucose decreased slightly and FFA and glycerol concentrations increased identically in all expts. Heart rate increased continuously during swimming in 27°C and 33°C expts., but not in 21°C expts. In conclusion the rise in body temperatures normally observed during exercise enhances the exercise induced increases in the plasma concentrations of noradrenaline, Cortisol, growth hormone and glucagon. Decreased body temperatures may elicit catecholamine secretion as a direct consequence of thermoreception. Shivering may account for previously observed decreases in insulin secretion during cold stress but not for increases in Cortisol and growth hormone.     

Increased glucagon secretion during hyperthermia in a sauna

Summary Plasma glucagon, adrenaline, noradrenaline, insulin and glucose concentrations were measured in 7 healthy young males during hyperthermia in a sauna bath: plasma glucagon levels increased from baseline values of 127.0±12.9 (SEM) pg · ml⁻¹ to a maximum of 173.6±16.1 (SEM) pg · ml⁻¹ at the 20th min of exposure. No change in plasma insulin and a slight increase in plasma glucose concentration were seen. Since a concomitant moderate increase in plasma catecholamine levels was also present, the adrenergic stimulus is believed to trigger glucagon release during hyperthermia. Diminished visceral blood flow, known to occur in sauna baths, may cause a decrease in the degradation of plasma glucagon and thus contribute to the elevated plasma glucagon levels.     

Secretion of Anterior Pituitary Hormones in Man: Effects of Ethyl Alcohol

The possibility that previously described effects of ethyl alcohol on peripheral endocrine glands might be mediated via pituitary prompted this investigation on the effects of ethanol on anterior pituitary secretion. Nine healthy male subjects were given beverage containing ethanol (1.5g/kg) or beverage alone per os in a randomized cross-over study and plasma ACTH, FSH, GH, LH and TSH were measured by specific radio-immunoassays up to 15 h and the urinary levels of adrenaline and noradrenaline by fluorometry. A combined LRF and TRF test was also carried out in similar series of experiments. During the whole experiment there were no significant differences in the plasma levels of ACTH, FSH and TSH or in the urinary levels of adrenaline and noradrenaline between ethanol treated and control subjects. Plasma FSH, LH and TSH responses to LRF and TRF stimulation were also similar in alcohol treated and control subjects. Plasma ACTH values were high (113–270 pg/ml) both in control and ethanol experiment suggesting that the subjects experienced apprehension toward the experiment. Plasma GH level exhibited a non-sleep related burst in the late evening (from 0.4 ng/ml at 6 p.m. to 3.1 ng/ml at 10 pm., p < 0.01). This increase was not seen after alcohol ingestion (p < 0.01). Plasma LH levels were significantly lower after 6 and 13 h in alcohol treated subjects than in controls (65 us, 106 ng/5ml, p < 0.01 and 74 us, 121 ng/ml, p < 0.05 respectively). Because ethanol had no effect on the resting level of plasma GH or on the LH response to LRF, we suggest that ethanol exerts these effects on a suprapituitary site.     

Secretion of anterior pituitary hormones in man: effects of ethyl alcohol.

The possibility that previously described effects of ethyl alcohol on peripheral endocrine glands might be mediated via pituitary prompted this investigation on the effects of ethanol on anterior pituitary secretion. Nine healthy male subjects were given beverage containing ethanol (1.5 g/kg) or beverage alone per os in a randomized cross-over study and plasma ACTH, FSH, GH, LH and TSH were measured by specific radioimmunoassays up to 15 h and the urinary levels of adrenaline and noradrenaline by fluorometry. A combined LRF and TRF test was also carried out in similar series of experiments. During the whole experiment there were no significant differences in the plasma levels of ACTH, FSH and TSH or in the urinary levels of adrenaline and noradrenaline between ethanol treated and control subjects. Plasma FSH, LH and TSH responses to LRF and TRF stimulation were also similar in alcohol treated and control subjects. Plasma ACTH values were high (113-270 pg/ml) both in control and ethanol experiment suggesting that the subjects experienced apprehension toward the experiment. Plasma GH level exhibited a non-sleep related burst in the late evening (from 0.4 ng/ml at 6 p.m. to 3.1 ng/ml at 10 p.m., p less than 0.01). This increase was not seen after alcohol ingestion (p less than 0.01). Plasma LH levels were significantly lower after 6 and 13 h in alcohol treated subjects than in controls (65 vs. 106 ng/ml, p less than 0.01 and 74 vs. 121 ng/ml, p less than 0.05 respectively). Because ethanol had no effect on the resting level of plasma GH or on the LH response to LRF, WE SUggest that ethanol exerts these effects on a suprapituitary site.     

Venous plasma adrenaline response to orthostatic syncope during tilting in healthy men

The effect of transient cerebral ischaemia connected with acute orthostatic hypotension on plasma adrenaline and noradrenaline levels was studied in seven healthy male volunteers during tilt. Sublingual administration of 1 mg nitroglycerin was used to block peripheral vascular reflexes and thus to provoke orthostatic intolerance. A consistent increase in plasma adrenaline concentrations (from 19.2 to 104.3 pg/ml on average, P less than 0.01) was found in six subjects who developed clinical signs of collapse after tilting. Plasma adrenaline never changed after tilting without collapse. Posturally stimulated plasma noradrenaline increases were similar yet irrespective of the presence of collapse.     

Metabolic and hormonal adjustments during hemorrhage in cats after interference with the sympatho-adrenal system

The relative contribution of the splanchnic sympathetic innervation and the adrenal medulla for metabolism and hormone secretion during two different levels of hemorrhagic hypotension was investigated in 3 groups of anesthetized cats, viz, intact, adrenalectomized and splanchnicotomized (adrenalectomy + cutting of splanchnic nerves). In intact cats, hemorrhage caused very marked elevations of arterial plasma glucose, adrenaline, noradrenaline, dopamine, lactate, cAMP, glycerol and glucagon concentrations whereas plasma insulin fell to only 20% of control values. Adrenalectomy attenuated the glucose, adrenaline, noradrenaline and cAMP responses whereas the normal insulin inhibition was abolished. Splanchnicotomy further reduced the hemorrhagic glucose and glycerol responses and, possibly, also that of glucagon. It is concluded that the adrenergic system as a whole is important for the adjustments of the release of glucose, cAMP, glycerol, insulin and glucagon that occur during hemorrhage in cats. The adrenal medulla seems to be of particular importance for the regulation of cAMP release.     

Family history of hypertension,exercise training,and reactivity to stress in rats

In this study we sought to assess the role of exercise training on blood pressure (BP) reactivity to tailshock stress in rats with varying family histories of hypertension. Exercise training consisted of swimming 90 min per day in isothermic water for either 2, 6, or 10 months, beginning at 2 months of age. Control subjects were age-matched and did not exercise daily. Rats with either zero (Wistar-Kyoto), 1 (borderline hypertensive), or 2 (spontaneously hypertensive) hypertensive parents were studied. At the appropriate age, femoral artery catheters were implanted and rats were studied at rest and in response to a 20-min stress session. Exercise training reduced basal BP, especially in rats with a positive family history that were exercised for the longest duration. Reactivity to stress was actually significantly enhanced in trained rats. Thus, these data do not support the reactivity hypothesis, but suggest several reasons why the literature has been so inconsistent. The discussion emphasizes the importance of basal, rather than phasic, BP responses resulting from exercise training. Research for this article was supported by National Institutes of Health (NIH) Grant No. HL19680 to James E. Lawler and NIH Grant No. HL34878 to Ronald H. Cox     

Endocrine responses to insulin hypoglycaemia in the young calf.

1. Variations in the output of glucocorticoids and catecholamines from the right adrenal gland, in response to insulin hypoglycaemia, have been investigated in calves 2-5 weeks after birth. These have been correlated with changes in the concentration of glucocorticoids and glucagon in arterial plasma. 2. Moderate hypoglycaemia for a limited period (0-1 u. insulin/kg), elicited a prompt increase in steroid output from the adrenal gland followed by a significant rise in plasma glucagon concentration. By comparison, changes in both catecholamine output and peripheral plasma glucocorticoid concentrations were found to be trivial in this group of animals. 3. Administration of a larger dose of insulin (0-5 u./kg) produced a more substantial fall in plasma glucose concentration followed by spontaneous recovery within 2-3 hr. This stimulus elicited the release of greater amounts of both cortisol and corticosterone, followed by a significant increase both in the output of adrenaline and in plasma glucagon concentration. Increase in steroid output was accompanied by an increase in adrenal blood flow and was associated with elevated concentrations of both steroids in arterial plasma. 4. The adrenal cortical response and associated changes in plasma steroid concentration were found to be transient even in response to persistent and intense hypoglycaemia (4 u. insulin/kg). The increase in plasma glucagon concentration in this group of animals was not significantly greater than that produced by smaller doses of insulin. However, substantial amounts of adrenaline (78 plus or minus 14 ng. kg-minus 1 min-minus 1; maximum; n equals 9) together with a little noradrenaline (10 plus or minus 3 ng.kg-minus 1 min-minus 1; maximum; n equals 9) were released from the right adrenal gland under these conditions. 5. Changes in adrenal blood flow could be related to adrenal glucocorticoid output in calves given 0-1 or 0-5 u. insulin/kg. In animals given the largest dose of insulin adrenal blood flow was found to increase coincidentally with rising steroid output but this hyperaemia then persisted after steroid output had subsided to values within the normal range. 6. Calves given the largest dose of insulin (4-0 u./kg) invariably collapsed and convulsed after 2-3 hr, but these symptoms could not be related to any particular endocrine response. No clinical signs of hypoglycaemia were observed in the other animals. 7. The results are discussed in relation to previous studies of adrenal function in this and other species.     

Diet induced changes in sympatho-adrenal activity during submaximal exercise in relation to substrate utilization in man

In order to study how the diet may influence sympatho-adrenal activity during exercise, 7 subjects were examined at rest and during submaximal exercise (25 min at 65% of VO2 max) on two occasions. The first occasion was preceded by 5 days on a carbohydrate poor diet (5% carbohydrate, 72% fat and 23% protein) and the second one by 5 days on a carbohydrate rich diet (78% carbohydrate, 8% fat and 14% protein) with the same energy content. Oxygen uptake, respiratory exchange ratio (R), heart rate and arterial plasma concentrations of adrenaline, noradrenaline, dopamine, insulin, glucose, lactate, free fatty acids (FFA), glycerol and beta-hydroxybutyrate were measured at rest and during exercise. Oxygen uptake and heart rate during exercise were higher and R was lower after the carbohydrate poor than after the carbohydrate rich diet. During exercise the arterial plasma concentrations of FFA, glycerol and beta-hydroxybutyrate were higher after the carbohydrate poor than after the carbohydrate rich diet whereas concentrations of insulin and lactate were lower. At rest arterial plasma noradrenaline and adrenaline levels were similar on the two diets (0.70 +/- 0.31 nM noradrenaline and 0.35 +/- 0.32 nM adrenaline one the carbohydrate rich diet, mean values +/- SD). Exercise induced increases in noradrenaline were more pronounced after the carbohydrate poor than after the carbohydrate rich diet (12.42 +/- 3.41 vs. 7.45 +/- 2.68 at 25 min of exercise, p less than 0.001). A similar, although more variable accentuation of exercise induced increases in adrenaline was found. It is concluded that, when compared to a carbohydrate rich diet, a carbohydrate poor diet increases the relative contribution of fat to oxidative metabolism and increases the sympatho-adrenal response to exercise. Stimulation of lipolysis by sympatho-adrenal mechanisms might be of importance for the substrate availability when carbohydrate intake in low.     

Glucoregulation and hormonal changes during prolonged exercise in boys and girls

A group of 17 children, 8.5–11 years old, performed a 60-min cycle exercise at 60% of maximal oxygen uptake (VO_2max) 2 h after a standardized breakfast. They were 10 young boys (pubertal stage =1) and 7 young girls (pubertal stage 2) of similarVO_2max (respective values were 48.5 ml min^–1 kg^–1, SEM 1.8; 42.1 ml min^–1 kg^–1, SEM 2.4). Blood samples of 5 ml were withdrawn by heparinized catheter, the subjects being in a supine position, 30 min before the test, then after 0, 15, 30 and 60 min of exercise and following 30 min recovery. Haematocrit was immediately measured. Thereafter plasma was analysed for glucose, non-esterified fatty acid, glycerol, catecholamine (noradrenaline, adrenaline), insulin and glucagon concentrations. This study showed two main results. First, the onset of exercise induced a significant glucose decrease (of about 11,4%) in all the children. Secondly, both the glycaemic and the hormonal responses were obviously different according to the sex. In boys only, the initial glucose drop was significantly correlated to the pre-exercise insulin values. Whatever the time, the glycaemic levels and the catecholamine responses were lower in girls than in boys, whereas the insulin values remained higher. However, none of these two hormonal parameters seemed to be really responsible for the lower glucose values in girls. On the one hand, the great individual variability of noradrenaline and adrenaline and differences in their relative intensity at the end of the exercise between boys and girls might contribute to the lower catecholamine levels in girls. On the other hand, the lack of a significant relationship in girls between the glucose decrease after exercise and the pre-exercise insulin values might be explained by a relative insulin insensitivity concomitant with the earlier growth spurt in girls, as demonstrated in subjects at rest by other authors. Finally the mechanisms of all these gender differences remain to be clarified and might be accounted for by a different maturation level in boys and girls.     

Plasma glucagon and catecholamines during exhaustive short-term exercise

Summary Plasma glucagon and catecholamine levels were measured in male athletes before and after exhaustive 15 min continuous running and strenuous intermittent short-term exercise (3×300 m). Blood lactate levels were higher after the intermittent exercise (mean 16.7 mmol×l^–1) than after the continuous running (mean 7.1 mmol×l^–1). Plasma glucagon concentration increased during continuous running and intermittent exercise by 41% and 55%, respectively, and the increases in plasma noradrenaline concentration were 7.7- and 9.1-fold compared with the respective pre-exercise values. Immediately after the exercises plasma cyclic AMP, blood glucose and alanine levels were elevated significantly.The data suggest that the sympathoadrenal system is of major importance for liver glucose production during high-intensity exercises. Catecholamines directly stimulate liver glucose production and may indirectly stimulate it by enhancing the secretion of glucagon.     

The effect of lesions of the sympathoadrenal system on training induced adaptations in adipocytes and pancreatic islets in rats

Physical training increases insulin stimulated glucose uptake in adipocytes and decreases insulin secretion from pancreatic islets. The mechanism behind these adaptations is not known. Because in acute exercise adrenergic activity influences both adipocytes and pancreatic islets, the sympathetic nervous system was examined as the possible mediator. Rats were either adrenodemedullated or sham adrenodemedullated and underwent either unilateral abdominal sympathectomy or were sham sympathectomized. Resting plasma adrenaline concentration in adrenodemedullated rats was 32% of the concentration in sham adrenodemedullated rats (P<0.0001) and muscle noradrenaline content in sympathectomized leg was 9% of content in sham sympathectomized leg (P<0.0001). After operations rats were either swim trained for 10 weeks or remained sedentary. Insulin stimulated 3-O-[¹⁴C]methylglucose transport was measured in adipocytes from epididymal fat pads, and insulin secretion and glucose metabolism were measured in glucose stimulated pancreatic islets. Training increased insulin stimulated glucose transport in adipocytes (P<0.0001) and decreased their size (P<0.0001), but neither adrenodemedullation nor sympathetic denervation affected these parameters significantly. Training decreased insulin secretion (P<0.01) and increased glucose oxidation (P=0.02) and utilization (P=0.08) in pancreatic islets, but none of these parameters was affected significantly by adrenodemedullation. It is concluded that adrenergic activity is not important for the training induced decrease in size and increase in insulin stimulated glucose transport of adipocytes. Neither is an intact adrenal medulla necessary for training-induced adaptations in pancreatic beta cell function. Finally, in response to training, β cell insulin secretion and glucose metabolism changed in opposite directions.     

Altered cardiovascular responsiveness to adrenaline in endurance-trained subjects

The influence of physical training on responses to i.v. adrenaline infusions and to exercise were investigated in 10 endurance-trained men (mean age: 35 y; VO2max: 61.9 ml kg-1 min-1) and 10 age-matched and sedentary controls (36 y, 37.5 ml kg-1 min-1). The untrained subjects were reinvestigated after a 4 month training period which increased their VO2max by 18%. Resting heart rate and diastolic blood pressure were significantly lower in the trained state. The venous plasma adrenaline concentrations attained during infusions (4 dose levels, 8 min each) were lower in the well-trained than in the untrained subjects (2.15 vs. 3.59 nmol l-1 at the highest dose level, P less than 0.01). The adrenaline-induced increases in heart rate and in plasma cAMP and decreases in pre-ejection period (PEP) and PEP/LVET ratio were not dependent on the training state. The adrenaline-induced decrease in diastolic blood pressure was more pronounced (P less than 0.05) in the well-trained than in the untrained group and tended (0.05 less than P less than 0.1) to be enhanced by training in the latter group. The increases in systolic blood pressure were greater in the well-trained subjects (P less than 0.01) but training did not alter this response in the untrained subjects. The plasma noradrenaline response to maximal cycle ergometer exercise (VO2max test) was significantly greater in the well-trained than in the untrained subjects, while no difference was seen for adrenaline. The submaximal exercise systolic blood pressure was similar in all training conditions when related to the absolute rate of work. In summary, the present results indicate that both the vasodilator and systolic pressor responses to adrenaline are enhanced in endurance-trained subjects. The cardiac chronotropic and inotropic effects of adrenaline seem, however, to be independent of the training state.     

The effect of exercise on platelet beta-adrenoceptor function and platelet aggregation in healthy human volunteers

Plasma levels of adrenaline and noradrenaline, platelet cyclic-AMP (cAMP) content, platelet aggregation, platelet release of beta-thromboglobulin, and platelet factor 4 and serum content of thromboxane B2(TXB2) and 6-keto-PGF1 alpha were measured in 12 healthy male volunteers (age 38-72, mean 54.2 years) who were tested at rest and immediately after five min light cycle exercise. The plasma levels of adrenaline and noradrenaline increased significantly after exercise (P less than 0.01). The platelet cAMP level was not changed by exercise. The functional capacity of platelet beta-adrenoceptors, determined as cAMP production after beta-adrenoceptor stimulation in vitro, decreased highly significantly after exercise in all 12 volunteers (P less than 0.01). No alteration was observed in platelet aggregation induced by adrenaline or in platelet release of beta-thromboglobulin or platelet factor 4. No change was observed in the serum levels of TXB2 and 6-keto-PGF1 alpha. In conclusion: light cycle exercise results in a decreased functional capacity of platelet beta-adrenoceptors, but has no effect on platelet aggregation or platelet release. This might indicate a concomitant and equal decreased functional capacity of platelet alpha-adrenoceptors.     

Plasma catecholamines in hepatic coma and liver cirrhosis: Role of octopamine

Summary Plasma levels of adrenaline, noradrenaline and octopamine were estimated by a radioenzymatic method in nine cirrhotic outpatients with encephalopathy and in ten patients with hepatic coma (coma grade III–IV). In the cirrhotic outpatients normal as well as elevated plasma levels of noradrenaline were found. Octopamine could not be detected in the plasma of these patients as well as of ten healthy volunteers. Elevated noradrenaline levels were present in all patients with hepatic coma. Plasma noradrenaline remained elevated or even further increased during the course of hepatic coma, whereas adrenaline was elevated less frequently. In eight of the ten patients with hepatic coma octopamine was again not detectable in plasma. Only in two patients high levels of octopamine up to 59.5 ng/ml could be found in addition to increased noradrenaline concentrations. The infusion of the branched chain amino acid L-valine had no influence on the plasma level of either noradrenaline or octopamine.The data indicate that the sympathetic nervous system is activated during the course of hepatic coma. An accumulation of octopamine is not a common finding in chronic liver disease and hepatic coma. Since in the two patients with elevated octopamine levels the rise in octopamine occured concomitantly with a rise in noradrenaline, a displacement of noradrenaline by the false neurotransmitter octopamine in the noradrenergic neuron of the peripheral sympathetic nervous system seems unlikely. The results indicate that the development of hypotension in the course of liver cirrhosis and hepatic coma cannot be related to a deficiency of noradrenaline.Deeply moved we have to inform the readers about the sudden death of our colleague and teacher Professor Dr. F. Wewalka     

Effects of the calcium antagonist felodipine on the sympathetic and renin-angiotensin-aldosterone systems in essential hypertension

Studies were performed in 10 male patients with untreated essential hypertension, WHO grade I-II, aged 25-62 years, to explore the acute (single dose) and long-term (8 weeks) effects of felodipine on sympathetic activity--evaluated by plasma and urinary catecholamines--as related to blood pressure, heart rate and the activity in the renin-angiotensin-aldosterone system. The patients were hospitalized for 8 (acute) and 6 (long-term) days and were maintained on a standardized daily intake of sodium (150 mmol), potassium (75 mmol) and water (2,500 ml). Acute felodipine administration (10 mg) significantly reduced blood pressure and increased heart rate. Plasma and urinary noradrenaline, plasma renin activity and angiotensin II increased, whereas plasma and urinary adrenaline, dopamine, aldosterone and plasma vasopressin were unaltered. Long-term felodipine treatment, 10 mg twice daily, reduced blood pressure to a similar extent as acute felodipine administration, but heart rate was not significantly changed. Plasma noradrenaline 3 and 12 hours after the last dose and urinary noradrenaline were increased, whereas plasma and urinary adrenaline and dopamine were unchanged. Plasma renin activity and angiotensin II were increased 3 hours, but unchanged 12 hours after the last dose. Plasma aldosterone was unchanged but urinary aldosterone increased. Plasma vasopressin was unchanged. The changes in plasma noradrenaline as related to blood pressure, heart rate, plasma renin activity and angiotensin II during long-term felodipine treatment may reflect decreased cardiac and renal beta-adrenoceptor-mediated responses. Increased renal clearance of aldosterone could partly explain the unaltered plasma aldosterone level in spite of increased plasma angiotensin II following long-term felodipine treatment.     

Effect of acute mild hypoxia during exercise on plasma free and sulphoconjugated catecholamines

Catecholamine (CA) response to hypoxic exercise has been investigated during severe hypoxia. However, altitude training is commonly performed during mild hypoxia at submaximal exercise intensities. In the present study we tested whether submaximal exercise during mild hypoxia compared to normoxia leads to a greater increase of plasma concentrations of CA and whether plasma concentration of catecholamine sulphates change in parallel with the CA response. A group of 14 subjects [maximal oxygen uptake, 62.6 (SD 5.2) ml · min^–1 · kg^–1 body mass] performed two cycle ergometer tests of 1-h duration at the same absolute exercise intensities [191 (SD 6) W] during normoxia (NORM) and mild hypoxia (HYP) followed by 30 min of recovery during normoxia. Mean plasma concentrations of noradrenaline ([NA]), adrenaline ([A]), and noradrenaline sulphate ([NA-S]) were elevated (P < 0.01) after HYP and NORM compared with mean resting values and were higher after HYP [20.9 (SEM 3.1), 2.2 (SEM 0.24), 8.12 (SEM 1.5) nmol · 1^–1, respectively] than after NORM [(13.7 (SEM 0.9), 1.5 (SEM 0.14), 6.8 (SEM 0.7) nmol · 1^–1, respectively P < 0.01]. The higher plasma [NA-S] after HYP (P < 0.05) were still measurable after 30 min of recovery. From our study it was concluded that exercise at the same absolute submaximal exercise intensity during mild hypoxia increased plasma CA to a higher extent than during normoxia. Plasma [NA-S] response paralleled the plasma [NA] response at the end of exercise but, in contrast to plasma [NA], remained elevated until 30 min after exercise.     

Plasma concentrations of adrenaline, noradrenaline and dopamine during forearm dynamic exercise

In six healthy volunteers plasma concentrations of adrenaline, noradrenaline and dopamine were measured at rest and during dynamic forearm exercise at submaximal and maximal intensities. Arterial and venous concentrations of adrenaline and noradrenaline increased with forearm exercise at all workloads. Dopamine concentrations did not change. The increases in adrenaline and noradrenaline were almost linearly related to the increase in heart rate with no levelling off at maximal exercise intensities. It is concluded that dynamic exercise with the forearm muscle group causes a small but significant activation of the sympatho-adrenal system as reflected by increases in plasma concentrations of adrenaline and noradrenaline.