Postural control following a self-initiated reaching task in type 2 diabetic patients and age-matched controls.

Although the postural stability of diabetic patients is affected in the presence of polyneuropathy, it has been suggested that diabetes per se has no effect on balance control during quiet standing. However, recent studies have reported muscular mechanical deficits in patients with type 2 diabetes (T2D) that may be highlighted during a more destabilizing task than quiet standing. Therefore, the objective of this study was to compare non-diabetic and T2D subjects during a modified version of the functional reach (FR) test in order to discriminate differences in postural control associated with diabetes per se. Thirty subjects (15 non-diabetic and 15 T2D) were requested to stand on a force platform and to perform the FR test. Center of pressure velocity (V(COP)), root-mean-square (RMS) amplitude and range of the COP were calculated in the anterior-posterior direction during three specific periods of the FR performance: namely "before", "on-going" and "after". No significant difference between the non-diabetic subjects and the T2D subjects was found for the FR performance. However, T2D subjects had significantly higher V(COP), RMS and range of COP displacements for the "after" period compared to the non-diabetic group (p<0.05). These results suggest that T2D subjects without peripheral neuropathy may have difficulties regaining their stability after a self-initiated reaching task. Therefore, diabetes mellitus per se, could have a direct effect on postural control during standing after a self-induced forward reaching movement.

Bradykinin facilitates noradrenaline spillover during contraction in the canine gracilis muscle.

Noradrenaline spillover from skeletal muscle vascular areas increases during exercise but the underlying mechanisms are not well understood. Muscle contraction itself causes changes in many factors that could affect noradrenaline spillover. For instance, it has been reported that bradykinin is synthesized in skeletal muscle areas during contraction. Because the B2 bradykinin receptor facilitates noradrenaline spillover, it may be involved in the increase associated with contraction. In this experiment, we studied the effect of bradykinin on noradrenaline spillover in the in situ canine gracilis muscle, using the specific B2 antagonist HOE 140. The drug did not modify noradrenaline spillover at rest, but did cause a significant decrease during muscle contraction, from 558 to 181 pg min(-1). As reported previously in the literature, fractional extraction of noradrenaline decreased during muscle contraction. This effect was independent of HOE 140 treatment. In light of our results, it seems that bradykinin formation during muscle contraction may play an important part in the observed increase in noradrenaline spillover but does not affect fractional extraction.

TGF-beta(1) and prepro-ANP mRNAs are differentially regulated in exercise-induced cardiac hypertrophy.

The induction of transforming growth factor (TGF)-beta and prepro-atrial natriuretic peptide (ANP) mRNAs represent hallmark features of pathological cardiac hypertrophy. The present study examined whether this pattern of mRNA expression was conserved in a physiological model of cardiac hypertrophy. To address this thesis, female Sprague-Dawley rats were individually housed and permitted to run freely. Voluntary exercise for 3 and 6 wk resulted in biventricular hypertrophy and increased cytochrome c oxidase activity in the triceps muscle. In the hypertrophied left ventricle, the steady-state mRNA level of the cardiac fetal gene prepro-ANP and the extracellular matrix proteins preprocollagen-alpha(1) and fibronectin were similar in exercise-trained and sedentary rats. By contrast, an increased expression of TGF-beta(1) mRNA was observed, whereas TGF-beta(3) mRNA level was unchanged in the hypertrophied left ventricle of exercise-trained compared with sedentary rats. These data highlight a heterogeneity in the regulation of TGF-beta isoforms, and the increased expression of ventricular TGF-beta(1) mRNA in physiological cardiac hypertrophy may contribute to myocardial remodeling.

Effect of blood flow and muscle contraction on noradrenaline spillover in the canine gracilis muscle.

Many authors have reported that, during exercise, noradrenaline spillover increases and fractional extraction decreases. It has been suggested that the increase in blood flow to active muscles may contribute to these effects. Muscle contraction also causes changes in many factors that may affect noradrenaline spillover and fractional extraction. In this experiment, we studied the effect of muscle contraction and blood flow on noradrenaline and adrenaline spillover and fractional extraction in the in situ canine gracilis muscle. The low intensity stimulation protocol enabled us to have muscle contractions without any effect on the local concentration of noradrenaline, as measured by microdialysis, and noradrenaline spillover. Fractional extraction of both noradrenaline and adrenaline was unaffected by increasing blood flow three and four times its resting value. In addition, noradrenaline spillover was increased by the higher blood flow, from 188 to 452 pg x min(-1) at rest and from 246 to 880 pg x min(-1) during stimulation. Stimulation of muscle contraction caused a significant increase in fractional extraction of noradrenaline and a nonsignificant increase in adrenaline extraction. In addition, an adrenaline spillover was observed in certain conditions. In light of our results, it seems that blood flow may not be the main factor decreasing fractional extraction of noradrenaline during exercise. However, blood flow could contribute to the increase in noradrenaline spillover observed in the active muscles during exercise.

Salbutamol effect in spinal cord injured individuals undergoing functional electrical stimulation training.

OBJECTIVE: Preliminary study to investigate possible changes in skeletal muscle morphology and function, as well as hormonal and metabolic effects, after treatment with a selective beta2-adrenergic receptor agonist. DESIGN: Double-blind, placebo-controlled trial. PARTICIPANTS: Three individuals with spinal cord injury (SCI). INTERVENTION: Two-week treatment with salbutamol (2mg) or placebo (ascorbic acid, 50mg) twice a day. Program of functional electronic stimulation (FES) cycling for 30 minutes twice a week. MAIN OUTCOME MEASURES: Body weight, three measures of leg circumference (gluteal furrow, one third of subischial height up from tibial-femoral joint space, and minimum circumference above the knee), muscle fiber area, and total work output per session. RESULTS: There were increases in body weight (2.30 +/- .70kg), leg circumferences (gluteal furrow 1.70 +/- .27cm, one third subischial height 1.53 +/- 1.65cm, minimum circumference above the knee .43 +/- .04cm), and muscle (vastus lateralis) cross-sectional area (1,374 +/- 493 to 2,446 +/- 1,177microm2) after salbutamol treatment, whereas quadriceps muscle contractile function was not modified. Total work output during FES cycling sessions was increased more during salbutamol treatment (64%) compared with training alone (27%). Salbutamol treatment was associated with a large decrease in skeletal muscle beta-adrenergic receptor density. CONCLUSION: Although some side effects were noted, these results suggest that a short treatment with the beta2-adrenergic receptor agonist salbutamol during a training program with FES cycling could be beneficial in patients with SCI.

Nifedipine does not impede clenbuterol-stimulated muscle hypertrophy.

The mechanism(s) responsible for beta2-adrenergic receptor-mediated skeletal muscle and cardiac hypertrophy remains undefined. This study examined whether calcium influx through L-type calcium channels contributed to the development of cardiac and skeletal muscle (plantaris; gastrocnemius; soleus) hypertrophy during an 8-day treatment with the beta2-adrenergic receptor agonist clenbuterol. Concurrent blockade of L-type calcium channels with nifedipine did not reverse the hypertrophic action of clenbuterol. Moreover, nifedipine treatment alone resulted in both cardiac and soleus muscle hypertrophy (6% and 7%, respectively), and this effect was additive to the clenbuterol-mediated hypertrophy in the heart and soleus muscles. The hypertrophic effects of nifedipine were not associated with increases in total beta-adrenergic receptor density, nor did nifedipine reverse clenbuterol-mediated beta-adrenergic receptor downregulation in either the left ventricle or soleus muscle. Both nifedipine and clenbuterol-induced hypertrophy increased total protein content of the soleus and left ventricle, with no change in protein concentration. In conclusion, our results support the hypothesis that beta2-adrenergic receptor agonist-induced muscle hypertrophy is mediated by mechanisms other than calcium influx through L-type calcium channels.

Chronic beta-blockade increases skeletal muscle beta-adrenergic-receptor density and enhances contractile force.

The effects of a chronic 14-day administration of a selective beta2-adrenergic-receptor antagonist (ICI-118551) on skeletal muscle were evaluated in female Sprague-Dawley rats. Chronic ICI-118551 treatment did not modify muscle mass, oxidative potential, or protein concentration of the medial gastrocnemius muscle, suggesting that maintenance of these skeletal muscle characteristics is not dependent on beta2-adrenergic-receptor stimulation. However, the drug treatment increased beta-adrenergic-receptor density of the lateral gastrocnemius (42%) and caused an increase in specific (g/g) isometric in situ contractile forces of the medial gastrocnemius [twitch, 56%; tetanic (200 Hz), 28%]. The elevated contractile forces observed after a chronic treatment with ICI-118551 were completely abolished when the beta2-adrenergic antagonist was also administered acutely before measurement of contractile forces, suggesting that this response is beta2-adrenergic-receptor dependent. Possible mechanisms for the increased forces were studied. Caffeine administration potentiated twitch forces but had little effect on tetanic force in control animals. Administration of dibutyryl adenosine 3',5'-cyclic monophosphate in control animals also resulted in small increases of twitch force but did not modify tetanic forces. We conclude that increases in beta-adrenergic-receptor density and the stimulation of the receptors by endogenous catecholamines appear to be responsible for increased contractile forces but that the mechanism remains to be demonstrated.

Clenbuterol has a greater influence on untrained than on previously trained skeletal muscle in rats.

The effects of clenbuterol, a selective beta 2-adrenergic agonist, and of exercise training on the properties of skeletal muscle were studied in the hindlimb of sedentary and trained rats. A 2-week training programme, consisting of climbing on a grid with a load attached to the tail, did not increase the muscle mass of the soleus, the plantaris and the gastrocnemius muscles or modify the isometric in situ contractile properties of the medial gastrocnemius muscle. The only change observed in a 12-week training regimen was a significant increase in contractile forces (expressed in grams per gram of muscle) of the medial gastrocnemius muscle at sub-tetanic stimulating frequencies (twitch 42%, 25Hz 45% and 50Hz 47%). Both training programmes significantly increased fatigue resistance of the medial gastrocnemius muscle. A 2-week oral treatment with clenbuterol significantly increased the muscle mass of the soleus (19.8%), plantaris (16.9%) and gastrocnemius (15.3%) muscles in all animals treated with the agonist. However, clenbuterol had different effects in animals beginning their training programme than in animals that had been trained for the previous 10 weeks. Specifically, clenbuterol caused a significant increase in gastrocnemius muscle mass in the former group but not in the latter. These results suggest that the responses to the combination of clenbuterol and training in previously trained skeletal muscles are not as marked as those observed in untrained muscles.

Detection of clenbuterol residues in hair.

Sixty rats were grown in the presence of 10 (n = 30) and 100 (n = 30) micrograms kg-1 body mass of clenbuterol for a period of 10 d. An immunoextraction step coupled with a competitive enzyme immunoassay allowed the quantification of clenbuterol in hair upon 20 (10 micrograms kg-1) and 30 d (10 micrograms kg-1) after the last dose. This accumulation in hair contrasts with the rapid clearance in tissues. The nature of the immunoreactive material was confirmed by mass spectrometry.

Atrial natriuretic peptide release from the ventricles in response to exercise in dogs with atrioventricular block.

The purpose of this study was to examine atrial natriuretic peptide (ANP) secretion at rest and in response to moderate treadmill exercise (10 min, 4 km/h, 26% slope) in control dogs (n = 17) and in dogs (n = 14) with complete atrioventricular block produced by electrocauterization of the His bundle. Atrial rates were similar in both groups (103 +/- 13 vs. 102 +/- 9 beats/min at rest and 162 +/- 10 vs. 160 +/- 17 beats/min at exercise in control dogs and in dogs with atrioventricular block, respectively; mean +/- SE), but ventricular rate was markedly lower in dogs with atrioventricular block (47 +/- 9 and 61 +/- 10 beats/min at rest and exercise, respectively). The lower ventricular rate was associated with an increased cardiac preload, as evidenced by the higher right atrial pressure in dogs with atrioventricular block at rest (2.2 +/- 1.4 vs. 1.1 +/- 0.9 mmHg; p < 0.05) and exercise (7.6 +/- 3.1 vs. 4.2 +/- 1.7 mmHg; p < 0.05). Arterial plasma ANP concentrations were markedly higher at rest (151 +/- 21 vs. 36 +/- 10 pg/mL; p < 0.05) and exercise (353 +/- 31 vs. 72 +/- 17 pg/mL; p < 0.05) in dogs with atrioventricular block. This observation supports the hypothesis that atrial wall stretching is a major stimulus for ANP release at rest and exercise. Ventricular release of ANP could also contribute to the higher plasma ANP concentrations observed both at rest and during exercise in dogs with complete atrioventricular block. Indeed, a large ANP concentration gradient was measured between the aorta and the distal part of the coronary sinus in these dogs at rest (227 +/- 55 pg/mL) and exercise (240 +/- 57 pg/mL) but not in control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Myoelectrical and metabolic changes in muscle fatigue.

In isometric contraction-induced fatigue force loss has been related to mostly myoelectrical or intramuscular events. However, some factors potentially involved may interfere at more than one site in these events and it has proven difficult to distinguish between those influences. The study of the relationships between force generating capacity, the metabolic state of a muscle and its myoelectrical properties may therefore help broaden our understanding of the fatigue process. In order to investigate these relationships, we have evaluated changes in force-generating capacity, NMR-determined metabolic variables, and myoelectrical activity, as measured from surface EMG, simultaneously in brachial biceps muscle of healthy subjects, during different types of fatiguing isometric exercise and during recovery. Factors studied include intramuscular pH, inorganic phosphate and its diprotonated form concentrations, root-mean square and mean power frequency of the EMG power spectrum, and neuromuscular efficiency index. Results show that different mechanisms are likely to contribute to force loss in fatiguing muscle and during different phases of recovery from fatigue. Indeed, relationships between variables from the three groups differed according to exercise protocol as well as in fatiguing and recovering muscle.

EMG spectral shift- and 31P-NMR-determined intracellular pH in fatigued human biceps brachii muscle.

We have simultaneously recorded human biceps brachii intracellular pH, estimated by 31P-NMR, and EMG spectral shift, during isometric contraction and recovery in six subjects. This method allows us to concurrently study several components of muscle fatigue. The results show a clear dissociation between the recovery of intracellular pH, force-generating capacity, and the shift to low frequency of the EMG power spectrum induced by fatiguing exercise.

6-OHDA sympathectomy and exercise performance in the rat.

6-hydroxydopamine (6-OHDA) was utilised for the study of the sympathetic nervous system in the resting rats and rats submitted to prolonged exercise. In order to reduce the acute physiological stress associated with an injection of 6-OHDA, beta-1 and alpha-1 adrenoceptors were blocked before the treatment leading to sympathectomy. Sympathectomised rats were divided in two groups: one sacrificed at rest, 24 hours after the treatment. The other group was sacrificed after a treadmill exercise to exhaustion. Running time to exhaustion was 36.0 +/- 4.5 min (mean +/- S.E.M.). This group ran significantly less than a control group brought to exhaustion in 73.7 +/- 10.0 min of exercise (P < 0.05). In order to make appropriate comparisons, another control group was run for 36 min. Some differences were observed between corresponding control and sympathectomized groups. At rest: 1) a lower plasma level of insulin, and 2) a higher plasma free fatty acid concentration were observed in sympathectomized rats. After 36 min of exercise: 1) a lower plasma concentration of norepinephrine, 2) no decrease of the plasma level of insulin, 3) no increase in the plasma glucagon concentration, and 4) a higher plasma glucose level were observed in sympathectomised rats when compared to control rats running for the same time. The lower plasma norepinephrine concentration in exercised sympathectomised rats suggests a lower sympathetic nervous activity in these animals than in control rats. The absence of a decrease of plasma insulin concentration and of an increase in glucagon can be attributed to this lower sympathetic activity in sympathectomised rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma catecholamines in the aorta and the phrenicoabdominal vein in exercising dogs.

Plasma epinephrine and norepinephrine concentrations were measured in the aorta and phrenicoabdominal vein in five dogs at rest and during short-duration mild- and moderate-intensity exercise and during prolonged mild-intensity exercise. Plasma epinephrine and norepinephrine concentrations increased with exercise in both the aorta and the phrenicoabdominal vein. Plasma epinephrine concentration was much higher in the phrenicoabdominal vein than in the aorta (24-43 times). Plasma epinephrine concentrations in the aorta and phrenicoabdominal vein were significantly correlated (r = 0.88). This confirms that peripheral epinephrine concentration is a reliable index of the activity of the adrenal medulla during exercise. The epinephrine-to-norepinephrine ratio in the phrenicoabdominal vein was stable (4:1) throughout the experimental protocol, suggesting that the proportion of the two amines released by the adrenal medulla did not vary through this range of adrenal activity in dogs.

Plasma atriopeptin during exercise in dogs under beta-blockade.

The purpose of this study was to describe plasma atriopeptin concentrations at rest and in response to moderate treadmill exercise (10 min, 4 km/h, 26% slope) performed with or without nonspecific beta-adrenergic blockade (1 mg/kg iv propranolol) in 10 mongrel dogs [19 +/- 2 (SE) kg]. A small (20%) but significant (P less than 0.05) increase in plasma atriopeptin concentration was observed from rest (43 +/- 5 pg/ml) to exercise (52 +/- 6 pg/ml) without beta-blockade. Propranolol significantly reduced heart rate at rest (89 +/- 7 vs. 104 +/- 7 beats/min) and during exercise (96 +/- 10 vs. 176 +/- 11 beats/min), and this was associated with a larger increase in plasma atriopeptin concentration during exercise (rest 46 +/- 6 pg/ml; exercise 171 +/- 22 pg/ml). Exercise under beta-blockade is associated with an increased preload of the heart. These results further support the hypothesis that atriopeptin release during exercise is under the control of atrial stretch. The higher plasma atriopeptin concentration observed during exercise under beta-blockade may contribute to the reduction of the response of plasma renin activity (1.0 +/- 0.1 vs. 3.0 +/- 0.6 ng.ml-1.h-1) and aldosterone concentration (87 +/- 36 vs. 138 +/- 25 pg/ml). Vasopressin concentration was lower at rest and during exercise under propranolol (3.5 +/- 1.3 vs. 4.9 +/- 0.9 and 6.1 +/- 2.2 vs. 9.9 +/- 1.5 pg/ml, respectively), which might reflect a dissociation between activity of the renin-angiotensin system and vasopressin release.

Metabolic and endocrine responses to prolonged exercise in rats under beta 2-adrenergic blockade.

The respective roles of allosteric regulators and catecholamines in the control of muscle glycogen breakdown during exercise remain a matter of controversy. This study was designed to reassess the role of the sympathoadrenal system during prolonged exercise in rats. Animals were studied at rest or after treadmill exercise (28 m.min-1; 8% slope) to exhaustion in a control situation or following administration of a specific beta 2-adrenergic receptor antagonist (ICI 118,551, 1 mg.kg-1, i.v.). Running times to exhaustion were 54 and 36 min in control and treated rats, respectively. For the purpose of comparison, another group of control rats was studied after a 36-min exercise bout. The reduction in endurance in treated rats was associated with an impairment in glycogen utilization, as measured by muscle glycogen stores, in soleus muscle but not in superficial vastus lateralis or gastrocnemius lateralis muscles. Utilization of liver glycogen stores was similar in the two groups of animals, but plasma glucose (7 vs. 13 mM) and lactate (4 vs. 7 mM) levels were significantly lower in rats under beta-blockade than in control rats run for 36 min. Plasma free fatty acid and glycerol concentrations were not significantly different between groups. On the other hand, plasma epinephrine concentration was significantly higher in treated rats (13 vs. 5 mM), which might reflect a compensatory increase in adrenal activity. These results suggest that glycogen breakdown during prolonged exercise is under the control of the sympathoadrenal system in predominantly slow-twitch but not in predominantly fast-twitch muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Sympatho-endocrine and metabolic responses to exercise under post-ganglionic blockade in rats.

The purpose of this study was to further document the role of locally released norepinephrine (NE) in the control of metabolic and endocrine responses to exercise in rats. Post-ganglionic blockade with bretylium (20 mg.kg-1, i.v.) reduced NE release from sympathetic nerve endings and triggered a compensatory increase in epinephrine (E) release from the adrenal medulla, as reflected by plasma NE and E concentrations at rest and exercise (E/NE ratio = 2.92 +/- 0.53 and 2.48 +/- 0.51 vs 0.62 +/- 0.15 and 1.48 +/- 0.18 in control rats; mean +/- SE). Following bretylium administration a reduction in running time to exhaustion (28 m.min-1, 8% slope: 33 +/- 2 min vs 74 +/- 10 min) was associated with 1) a faster decrease in blood glucose concentration (3.58 +/- 0.80 mM vs 8.09 +/- 0.38 mM in control rats exercised for 33 min); and 2) an increased glycogen store utilization in fast-twitch muscles (superficial vastus lateralis and gastrocnemius lateralis). Glycogen utilization was not modified in soleus muscle and in the liver. Taken together these results suggest that post-ganglionic blockade increased carbohydrate store and peripheral blood glucose utilization. This could reflect an impairment in fat mobilization and utilization which might be secondary to a reduction of NE release in the adipose tissue and/or in the endocrine pancreas.

Regional plasma catecholamine removal and release at rest and exercise in dogs.

Dynamics of circulating catecholamines (CA) were studied at rest (heart rate = 104 +/- 3 beats/min) and during mild treadmill exercise (heart rate = 168 +/- 5 beats/min) in 60 dogs. Plasma epinephrine (E) and norepinephrine (NE) removal from circulation and release into circulation were estimated from plasma CA arteriovenous differences across the regional vascular beds studied (pulmonary, myocardial, hepatosplanchnic, renal, and skeletal muscle vascular beds) and from regional blood flows. Regional plasma E fractional extraction (PEFE) was used as an index of NE removal from plasma. Arterial plasma CA increased significantly from rest to exercise (P less than 0.05). A significant PEFE was observed at rest and exercise across all studied vascular beds but the pulmonary bed. When plasma flow was taken into account, the largest contributors to plasma CA removal were the hepatosplanchnic vascular bed at rest and skeletal muscle vascular beds during exercise. At rest, the hepatosplanchnic vascular bed was a major contributor to the plasma NE pool. During exercise, main contributors to NE release into plasma were skeletal muscle vascular beds. Circulating CA kinetics did not appear to vary from rest to exercise. Clearance and apparent distribution space were estimated to be, respectively, 1.5 l/min and 2 liters for circulating E and 2 l/min and 5 liters for NE at rest and exercise. Circulating E and NE half times were estimated to be approximately 1 and 1.8 min, respectively.