Biomedical subjects

P Hespel

Publications and source records attributed to P Hespel.

At least 55 records · Page 3Linked to original sources

PubMed1993

Glucose transport and transporters in muscle giant vesicles: differential effects of insulin and contractions.

Collagenase treatment of skeletal muscle results in the formation of large spheres of membranes (3-30 microns diam). A procedure is described for purification and concentration of these giant membrane vesicles prepared from rat muscle. Morphological observations, marker enzyme analysis, and immunoblotting demonstrate that the vesicles are of plasma membrane origin and that sarcoplasmic reticulum, T-tubules, and mitochondrial inner membranes are absent from the preparation. Western blots demonstrate that the vesicles contain GLUT-4 glucose transporters, whereas GLUT-1 could not be detected. Vesicles prepared from control muscle display specific transport of D-glucose with a maximum velocity (Vmax) for glucose influx of approximately 2,500 pmol.mg plasma membrane protein-1.s-1 and an apparent Michaelis constant (Km) of 16 mM measured at zero-trans conditions at room temperature. Muscle contractions in vivo doubled the Vmax of vesicle glucose transport and membrane GLUT-4 content but did not change Km. In contrast, in vivo administration of insulin did not affect vesicle glucose transport or membrane GLUT-4 content. The combination of insulin and contractions caused similar changes as did contractions alone. It is concluded that the present vesicle population contains membrane components almost exclusively derived from the plasma membrane and contains very little if any GLUT-1 but substantial amounts of GLUT-4. Thus the preparation allows the study of transport kinetics of pure GLUT-4 transporters. The procedure for preparing vesicles probably results in activation of the glucose transport system similar to the activation by insulin but not by contractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Mechanism linking glycogen concentration and glycogenolytic rate in perfused contracting rat skeletal muscle.

The influence of differences in glycogen concentration on glycogen breakdown and on phosphorylase activity was investigated in perfused contracting rat skeletal muscle. The rats were preconditioned by a combination of swimming exercise and diet (carbohydrate-free or carbohydrate-rich) in order to obtain four sub-groups of rats with varying resting muscle glycogen concentrations (range 10-60 mumol/g wet wt.). Pre-contraction muscle glycogen concentration was closely positively correlated with glycogen breakdown over 15 min of intermittent short tetanic contractions (r = 0.75; P less than 0.001; n = 56) at the same tension development and oxygen uptake. Additional studies in supercompensated and glycogen-depleted hindquarters during electrical stimulation for 20 s or 2 min revealed that the difference in glycogenolytic rate was found at the beginning rather than at the end of the contraction period. Phosphorylase alpha activity was approximately twice as high (P less than 0.001) in supercompensated muscles as in glycogen-depleted muscles after 20 s as well as after 2 min of contractions. It is concluded that glycogen concentration is an important determinant of phosphorylase activity in contracting skeletal muscle, and probably via this mechanism a regulator of glycogenolytic rate during muscle contraction.

Animals↗

PubMed1992

Effect of physical training on systemic and brachial artery haemodynamics in normal men.

The effect of endurance training on resting systemic and brachial haemodynamics was studied in 27 normal sedentary volunteers using a randomized cross-over design. After four months of physical training, peak oxygen uptake and physical working capacity at a heart rate of 130 beats/min (PW130) were increased by 16% (p less than 0.01) and 29% (p less than 0.001), respectively. At end-diastole left ventricular wall thickness was increased (p less than 0.01), whereas internal diameter was not changed. However, the change in internal diameter was positively related (r = 0.44, p less than 0.036) to the change in PWC130, indicating that the internal diameter increased, particularly in those subjects with the greatest increase in exercise capacity. The systemic haemodynamic adaptation to training was characterized by an increased stroke volume and concomitant reduction in heart rate so that cardiac output was not changed. On the other hand, brachial blood flow decreased by 36% on average. The change in blood flow was negatively related (r = -0.43, p = 0.03) to the change in PWC130 after training. Half the number of subjects were restudied after a four-month detraining period. The echocardiographic and Doppler variables tended to return to the pretraining level.

Adult↗

PubMed1992

Metabolic responses to exercise. Effects of endurance training and implications for diabetes.

In this study, some important metabolic responses to exercise will be discussed, and aspects of particular interest for patients with diabetes mellitus will be emphasized. Alterations in the metabolic responses to exercise induced by physical endurance training and consequences of training for metabolism of plasma lipids and lipoproteins will be discussed. Glucoregulation during exercise is not perfect in normal subjects and is less so in patients with diabetes mellitus. For instance, during intense exercise, large increases in the plasma glucose concentration occur and a state of insulin resistance exists for a few hours after intense exercise. Even so, increased sensitivity to insulin is found the day after intense exercise and also shortly after more moderate intensity exercise, both in healthy subjects and in patients with diabetes mellitus. Increased sensitivity to insulin is also found after endurance training, whereas insulin sensitivity is decreased after inactivity. Exercise training increases the ability of muscle to take up and oxidize free fatty acids during exercise and also increases the activity of the enzyme lipoprotein lipase in muscle. The activity of lipoprotein lipase in muscle correlates with muscle insulin sensitivity. This might explain why insulin resistance is often associated with hypercholesterolemia, hypertriglyceridemia, and low high-density lipoprotein cholesterol.

Blood Glucose↗

PubMed1990

Glucose uptake and transport in contracting, perfused rat muscle with different pre-contraction glycogen concentrations.

1. Glucose uptake and transport, muscle glycogen, free glucose and glucose-6-phosphate concentrations were studied in perfused resting and contracting rat skeletal muscle with different pre-contraction glycogen concentrations. Rats were pre-conditioned by a combination of swimming exercise and diet, resulting in either low (glycogen-depleted rats), normal (control rats) or high (supercompensated rats) muscle glycogen concentrations at the time their hindlimbs were perfused. 2. Compared with control rats, pre-contraction muscle glycogen concentration was approximately 40% lower in glycogen-depleted rats, whereas it was 40% higher in supercompensated rats. Muscle glycogen break-down correlated positively (r = 0.76; P less than 0.001) with pre-contraction muscle glycogen concentration. 3. Glucose uptake during contractions was approximately 50% higher in glycogen-depleted hindquarters than in control hindquarters; in supercompensated hindquarters it was 30% lower. When rats with similar muscle glycogen concentrations were compared, glucose uptake in hindquarters from rats that had exercised on the preceding day was approximately 20% higher than in hindquarters from rats that had not exercised on the preceding day. 4. Muscle membrane glucose transport, as measured by the rate of accumulation of 14C-3-O-methylglucose in the contracting muscles, was 25% lower in supercompensated than in glycogen-depleted muscles at the onset as well as at the end of the 15 min contraction period. 5. Intracellular concentrations of free glucose and glucose-6-phosphate were higher at rest and during the entire 15-min stimulation period in supercompensated muscles than in glycogen-depleted muscles, and glucose uptake during contractions correlated negatively with free glucose (r = -0.52; P less than 0.01) as well as with glucose-6-phosphate (r = -0.49; P less than 0.01) concentrations. 6. It is concluded that: (a) The rate of glucose uptake in contracting skeletal muscle is dependent on the pre-contraction muscle glycogen concentration. Regulating mechanisms include limitations of membrane glucose transport as well as of glucose metabolism. (b) Contractions on the preceding day have a stimulating effect on glucose uptake during contractions of the same muscles on the next day.

3-O-Methylglucose↗

PubMed1989

Effect of endurance training on blood pressure at rest, during exercise and during 24 hours in sedentary men.

The effect of 4 months of physical training on resting, exercise and 24-hour blood pressure (BP) was studied using a randomized crossover design in 26 healthy, sedentary men, with an average age of 39 +/- 10 (standard deviation) years. Peak oxygen uptake increased by 14% (p less than 0.001) and the physical working capacity at a heart rate of 130 beats/min by 25% (p less than 0.001). The heart rate was reduced by 7 beats/min at night (p less than 0.01) and by 6 beats/min during the day (p less than 0.001). Training-induced changes of BP varied according to measuring conditions. A decrease in BP at rest while sitting in the morning in the laboratory was significant for diastolic (-5 mm Hg, p less than 0.01) but not for systolic BP. During exercise, systolic BP was significantly lower after training, when measured at the same submaximal workloads. However, when workload was expressed as a percentage of peak oxygen uptake, systolic BP was not different before and after training. When measured during 24 hours, the training-induced change in BP was not significant at night either for systolic or diastolic BP. During the day the decrease in diastolic BP was significant (-5 mm Hg, p less than 0.001), but the change in systolic BP was not.

Adult↗

PubMed1989

Plasma atrial natriuretic peptide and the renin-aldosterone system during long-term administration of the diuretic xipamide in man.

We have studied the effect of xipamide on plasma alpha-atrial natriuretic peptide and the renin-aldosterone-kallikrein system in twelve healthy men, using a double-blind cross-over design. After a run-in period on placebo for 1 week the subjects were treated with either placebo (n = 6) or xipamide 20 mg once daily (n = 6) for 16 weeks and were then switched to the alternative medication for another 16 weeks. The plasma concentration of alpha-atrial natriuretic peptide fell after 1 week of xipamide administration and increased during prolonged xipamide administration but remained suppressed. The changes in plasma alpha-ANP observed after 1 week of xipamide were negatively correlated with the changes in haematocrit and haemoglobin. Plasma renin activity (PRA), aldosterone concentration (PAC), and urinary excretion of aldosterone and kallikrein increased after 1 week of xipamide administration, levelled off during the second and fourth weeks, but remained elevated during further prolonged xipamide administration for 16 weeks. The xipamide-induced changes in PRA and PAC were positively correlated with the changes in the haematocrit and haemoglobin. Our data suggest that the changes in plasma renin, aldosterone, and alpha-atrial natriuretic peptide during xipamide administration may be related to diuretic-induced volume contraction.

Aldosterone↗

PubMed1989

Acute calcium entry blockade inhibits the blood pressure but not the hormonal responses to angiotensin II.

The effects of acute calcium entry blockade by isradipine (IS) and placebo (P) on the haemodynamic and humoral responses to angiotensin II (A II) have been compared in two groups of 9 patients with essential hypertension. During 4 sequential periods each of 20 min, an i.v. infusion of A II 0, 2, 4 and 8 ng.kg-1.min-1 was given before (control) and 30 min after the oral administration either of IS or P. After IS, both the blood pressure and the angiotensin II-induced pressor effect were significantly reduced. Isradipine increased the heart rate and this cardio-acceleration was potentiated by A II. In contrast, when A II was infused in the absence of IS, heart rate tended to decrease. IS stimulated plasma renin activity and reduced plasma aldosterone. However, it did not affect either the inhibition of plasma renin activity or the rise in plasma aldosterone in response to A II. In conclusion, acute calcium entry blockade in patients with essential hypertension reduces the pressor response to A II, but not the A II-induced inhibition of renin and increase in plasma aldosterone.

Adrenocorticotropic Hormone↗

PubMed1989

Effect of prolonged physical exercise on intra-erythrocyte and plasma potassium.

The intracellular concentrations of sodium [Na+] and potassium [K+] and the water content in human erythrocytes were investigated in 21 male runners before and after a marathon. From 2 to 5 min after the race, the intra-erythrocyte [K+] was significantly decreased (p less than 0.001) by 7% whereas the plasma [K+], intra-erythrocyte [Na+] and the erythrocyte water content were unchanged. The change in the intra-erythrocyte [K+] observed immediately after the marathon, was negatively correlated with the race time (r = -0.44; p less than 0.05). Furthermore, the change in the plasma [K+] (r = -0.64; p less than 0.001) and the amount of K+ excreted in the urine during the race (r = 0.54; p less than 0.05) were also, respectively, negatively and positively correlated with the race time. It is concluded that during prolonged physical exercise the erythrocytes could serve as a kind of K+ reservoir that is drained with increasing magnitude of body K+ loss. This might explain why in the faster marathon runners, in whom the urinary K+ loss is smaller and the K+ intake is greater than in the slower runners during race, the intra-erythrocyte [K+] is unchanged after a marathon whereas in the slower runners it is decreased.

Adult↗

PubMed1989

Carotid baroreflex sensitivity at rest and during exercise is not influenced by opioid receptor antagonism.

Physical effort involves, along with an increase in the plasma concentration of beta-endorphin, profound cardiovascular adaptations. The aim of the present study was to investigate with the use of the variable neck chamber technique, the influence of the endogenous opioids on the carotid baroreflex control of blood pressure and heart rate at rest as well as during exercise. Ten normal volunteers exercised in the supine position up to 33% and 66% of their maximal exercise capacity and received, in a randomized double-blind cross-over protocol, either saline or naloxone (10 mg intravenously, followed by a continuous infusion of 10 mg.h-1). During exercise a progressive attenuation of the carotid baroreceptor reflex control of blood pressure and heart rate was noted. However, neither at rest nor during exercise, did opioid antagonism influence the carotid baroreceptor control of blood pressure and heart rate. Intra-arterial pressure and heart rate also remained unaffected. In contrast, both at rest and during exercise, naloxone administration produced a significant increase in the plasma concentration of cortisol. The latter suggests that in vivo the opioid receptors were effectively antagonized. In conclusion the present study confirms that opioids play only a minor role in cardiovascular homeostasis at rest. In addition, this study demonstrates that they are not involved in the cardiovascular adaptation to exercise, nor in the exercise-related attenuation of the carotid baroreceptor control of pressure and heart rate.

Adult↗

PubMed1989

Effects of the new calcium entry blocker isradipine (PN 200-110) in essential hypertension.

In this double-blind cross-over study 16 patients with mild-to-moderate hypertension were treated with placebo and the dihydropyridine derivative, isradipine 5-10 mg twice daily. In the supine position isradipine reduced systolic (-18 mm Hg; p less than 0.002) and diastolic (-15 mm Hg; p less than 0.001) pressures, while heart rate was not changed; in the standing position, systolic (-15 mm Hg; p less than 0.002) and diastolic (-14 mm Hg; p less than 0.001) pressures decreased, whereas heart rate increased (+6 bpm; p less than 0.05). Body weight and lower leg volumes remained unaltered, suggesting that isradipine did not cause fluid retention. On IS plasma angiotensin I (+40 pg/ml), angiotensin II (+ 14 pg/ml), and aldosterone (+4.1 ng/dl) rose. The intracellular Na+ and K+ concentrations and the transmembrane cation transport activities (Na+-K+ pump, Na+-K+ cotransport, Na+-Li+ countertransport), measured ex vivo in the erythrocytes of eight male patients, were not significantly influenced by isradipine. Hot flushes and facial erythema occurred more frequently (p less than 0.05) on isradipine than on placebo. In conclusion, the new calcium entry blocker isradipine at a dose of 5-10 mg twice daily lowers blood pressure and is well tolerated in most patients with essential hypertension.

Blood Pressure↗

PubMed1988

Erythrocyte, plasma and urinary magnesium in men before and after a marathon.

Erythrocyte, plasma and urinary magnesium (Mg2+) concentration was measured in 23 runners before and after a marathon race. Blood samples were drawn from an antecubital vein the morning before the race (baseline), at 3 p.m. (2 h before the start), upon finishing and 12 h later. Compared with the baseline values, the intra-erythrocyte and plasma Mg2+ were decreased (p less than 0.05 or less) immediately after the marathon, from 2.13 +/- 0.16 to 2.02 +/- 0.18 mmol.l-1 cells and from 0.88 +/- 0.06 to 0.81 +/- 0.07 mmol.l-1 respectively. The Mg2+ concentration returned to pre-race values 12 h after completion of the marathon. The urinary Mg2+ excretion rate decreased (p less than 0.001) from 29 +/- 13 to 5 +/- 3 mumol.min-1 during the marathon and increased (p less than 0.05) 12 h after the race to 38 +/- 18 mumol.min-1. It is concluded that the reduction in plasma Mg2+ ion concentration during the marathon cannot be attributed to erythrocyte uptake, urinary excretion or loss in sweat. It is suggested that Mg2+ may be released from erythrocytes into the extracellular fluids during sustained exercise and taken up from these fluids by the adipose cells.

Adolescent↗

PubMed1988

Erythrocyte 2,3-diphosphoglycerate concentration before and after a marathon in men.

Erythrocyte 2,3-diphosphoglycerate (2,3-DPG) concentration was studied in 23 runners before and after a marathon race. Blood samples were drawn from an antecubital vein the morning before the race (baseline), at 3 p.m. 2 h before the start, on finishing, and 12 and 36 h later. Compared to the baseline values, erythrocyte 2,3-DPG concentration was increased (p less than 0.001) immediately after the marathon from 4.62 +/- 0.14 to 5.56 +/- 0.13 mumol.ml-1 RBC and remained elevated 12 h later (5.45 +/- 0.14 mumol.ml-1 RBC): it returned to prerace values 36 h after completion of the marathon.

2,3-Diphosphoglycerate↗

PubMed1988

Effects of training on erythrocyte 2,3-diphosphoglycerate in normal men.

The erythrocyte 2,3-diphosphoglycerate concentration (2,3-DPG) and the activity of red cell hexokinase, pyruvate kinase, glucose-6 phosphate dehydrogenase and glutathione reductase were studied in 27 normal volunteers before and after 2 and 4 months of physical endurance training. The 4 months of training increased maximal oxygen uptake and physical working capacity (PWC130) by 16% (p less than 0.001) and 29% (p less than 0.001) respectively. Resting heart rate was decreased (p less than 0.001) by 11 beats.min-1. With 2 months of training the erythrocyte 2,3-DPG concentration increased by 9% (p less than 0.001); with 4 months training the increase was only 4% (p less than 0.05). The training-induced increase in red cell 2,3-DPG was not accompanied by enhanced activity of erythrocyte hexokinase, pyruvate kinase, glucose-6 phosphate dehydrogenase or glutathione reductase. It is concluded that the rise in red cell 2,3-DPG induced by physical endurance training is not due to activation of red cell glycolytic enzymes or the enzymes involved in the pentose-phosphate cycle.

2,3-Diphosphoglycerate↗

PubMed1988

Changes in plasma lipids and apoproteins associated with physical training in middle-aged sedentary men.

The effect of endurance training on plasma lipoproteins was investigated in 27 healthy sedentary men between the ages of 20 and 55 years. During the first 4 months of the study, 13 of them (group A) participated in a training program (3 hours/wk), whereas the others served as control subjects (group B). At the end of this period the control subjects also underwent a 4-month training program. In both groups the training significantly increased physical working capacity at a heart rate of 130 bpm (PWC130), whereas it decreased the resting heart rate (p less than 0.05). Concomitantly with this improvement in cardiorespiratory fitness, a significant increase in the high-density lipoprotein (HDL) cholesterol concentration was observed (p less than 0.01); this was due to an increase in both HDL2 beta and HDL2 alpha + 3 cholesterol concentrations. The plasma total and HDL-apoprotein AI and apoprotein AII concentrations were not significantly affected by the training. Significant decreases in plasma triglyceride (p less than 0.05), very-low-density lipoprotein cholesterol (p less than 0.05), and low-density lipoprotein (LDL) cholesterol (p less than 0.001) concentrations were also observed, but only in group B, which showed a much greater increase in PWC130 at the end of the training period than group A; the decrease in the LDL cholesterol concentration in this group was accompanied by a slight decrease in the LDL-apoprotein B concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Effects of opioid antagonism on the haemodynamic and hormonal responses to exercise.

1. Physical effort involves, along with an increase in the plasma concentration of beta-endorphin, profound adaptations of the circulation and the endocrine system. The effects of opioid antagonism on the responses of blood pressure, heart rate and several hormones to exercise were therefore studied in 10 normal men. They exercised in the supine position up to 33% and 66% of their maximal exercise capacity and received in a randomized double-blind cross-over protocol, either saline or naloxone (10 mg intravenously, followed by a continuous infusion of 10 mg/h). 2. Intra-arterial pressure and heart rate were continuously monitored, but were not affected by naloxone. 3. At rest, opioid antagonism produced a rise in plasma renin activity and in plasma adrenocorticotropin, cortisol and aldosterone, but only the stimulation of the two adrenocortical hormones differed significantly from the control experiments; at rest naloxone also prevented the fall in plasma adrenaline, which occurred with saline infusion. Furthermore, the exercise-induced rises in plasma angiotensin II, aldosterone, cortisol, noradrenaline and adrenaline were higher on naloxone than on saline, while a similar tendency was also present for the increases with exercise in plasma renin activity and plasma adrenocorticotropin. Neither at rest nor during exercise did opioid antagonism alter plasma lactate and glucose and serum insulin and growth hormone. 4. In conclusion, (1) endogenous opioids are not involved in the responses of blood pressure and heart rate to supine exercise; (2) at rest and during exercise, the endogenous opioids inhibit the secretion of adrenocorticotropin, aldosterone, cortisol, noradrenaline and adrenaline; (3) they also inhibit the plasma renin-angiotensin II system indirectly via the catecholamines.

Adrenal Cortex Hormones↗

PubMed1988

Indicators of cell breakdown in plasma of men during and after a marathon race.

Plasma indicators of muscle cell leakage and of hemolysis were studied in 23 runners before and after a marathon race. Blood samples were drawn from an antecubital vein the morning before the race (baseline), at 3 p.m., i.e., 2 h before the start, on arrival, 12 and 36 h, and 7 days later. Compared with the baseline values, the plasma creatinine phosphokinase MM and MB subfractions, aldolase and glutamicoxaloacetic transaminase activity were increased immediately after the race, rose further 12 h after the marathon, and remained elevated the race, rose further 12 h after the marathon, and remained elevated 36 h and 7 days later. The plasma lactate dehydrogenase activity and myoglobin concentration were increased on arrival and returned to the pre-race activity 7 days after the marathon. Compared with the pre-race values, the plasma haptoglobin concentration was decreased immediately and 12 h after the marathon. Our data show that indicators of muscle cell leakage and of hemolysis in plasma, withdrawn after a marathon race, remained elevated for up to 7 days after the race.

Adult↗

PubMed1988

Erythrocyte and leucocyte sodium and potassium transport systems during long-term diuretic administration in men.

The effect of xipamide on the intracellular concentration and transmembrane fluxes of Na+ and K+ was studied in 12 normal male subjects, using a double-blind cross-over design. After a run-in period on placebo for 1 week, the subjects were treated with either placebo (n = 6) or xipamide 20 mg once a day (n = 6) for 16 weeks and were then switched to the alternative medication for another 16 weeks. The intra-erythrocyte and intra-leucocyte Na+ concentration was increased by 11 and 7%, respectively, during xipamide administration, while the intracellular K+ concentration was decreased by 3 and 4%, respectively. No significant effect of xipamide could however be demonstrated on the ouabain-sensitive, bumetanide-sensitive or ouabain-bumetanide-resistant 86Rb uptake and on the maximal 3H-ouabain binding in erythrocytes and leucocytes. The red cell Na+-Li+ countertransport was also not changed in the xipamide-treated subjects. Our data suggest that the increased intracellular Na+ concentration and the decreased K+ concentration in red and white blood cells of xipamide-treated subjects cannot be attributed to changes in the activity of the Na+ pump, the Na+-K+ cotransport or Na+-Li+ countertransport system or to changes in the number of active Na+ pump units.

Adult↗