Effects of exercise and beta 2-agonists on lung function in chronic obstructive pulmonary disease.

The effects of inhaled bronchodilators at rest and during exercise were studied in 15 subjects with chronic obstructive pulmonary disease. In a crossover study against placebo, albuterol caused a significant increase in expiratory flow and reduced lung hyperinflation and dyspnea at rest, but this was not associated with differences in symptoms with exercise or any relevant parameter of physical performance. Dynamic hyperinflation occurred during exercise similarly after placebo or albuterol and was associated with a reduction of forced expiratory flows. This, in turn, was correlated with the bronchoconstrictor effect of deep inhalation determined at rest. In a parallel group study, expiratory flow was increased by 3-wk treatment with salmeterol (n = 9) but not with placebo (n = 6). However, in neither group was the response to exercise different from baseline. These results suggest that in chronic obstructive pulmonary disease effective pharmacological bronchodilation at rest may not be predictive of benefits of exercise tolerance. This may be related to the occurrence of airway narrowing during exercise, particularly when a deep inhalation at rest is followed by a decrease in expiratory flow.     

Effects of exercise and lifestyle intervention on oxidative stress in chronic kidney disease

Objectives: Determine the effects of a 12-month exercise and lifestyle intervention program on changes in plasma biomarkers of oxidative stress in pre-dialysis chronic kidney disease (CKD) patients.

Methods: A total of 136 stage 3–4 CKD patients were randomized to receive standard nephrological care with (N?=?72) or without (N?=?64) a lifestyle and exercise intervention for 12 months. Plasma total F₂-isoprostanes (IsoP), glutathione peroxidase (GPX) activity, total antioxidant capacity (TAC), anthropometric and biochemical data were collected at baseline and at 12 months.

Results: There were no significant differences between groups at baseline. There were no significant differences in changes for standard care and lifestyle intervention, respectively, in IsoP (p?=?0.88), GPX (p?=?0.87), or TAC (p?=?0.56). Patients identified as having high IsoP at baseline (>250 pg/mL) had a greater decrease in IsoP with lifestyle intervention compared to standard care; however, the difference was not statistically significant (p?=?0.06). There was no difference in the change in kidney function (eGFR) between standard care and lifestyle intervention (p?=?0.33).

Discussion: Exercise and lifestyle modification in stage 3–4 CKD did not produce changes in systemic biomarkers of oxidative stress over a 12-month period, but patients with high IsoP may benefit most from the addition of intervention to standard care.     

Effects of exercise training on quadriceps muscle gene expression in chronic obstructive pulmonary disease.

Exercise capacity and training response are limited in chronic obstructive pulmonary disease (COPD), but the extent to which this is related to altered skeletal muscle function is not fully understood. To test the hypothesis that muscle gene expression is altered in COPD, we performed needle biopsies from the vastus lateralis of six COPD patients and five sedentary age-matched healthy men, before and after 3 mo of exercise training. RNA was hybridized to Affymetrix U133A Genechip arrays. In addition, peak O(2) uptake and other functional parameters (e.g., 6-min walk) were measured before and after training. The 6-min walk test increased significantly following training in both groups (53.6 +/- 18.6 m in controls, P = 0.045; 37.1 +/- 6.7 m in COPD, P = 0.002), but peak O(2) uptake increased only in controls (19.4 +/- 4.5%, P = 0.011). Training significantly altered muscle gene expression in both groups, but the number of affected genes was lower in the COPD patients (231) compared with controls (573). Genes related to energy pathways had higher expression in trained controls. In contrast, oxidative stress, ubiquitin proteasome, and COX gene pathways had higher expression in trained COPD patients, and some genes (e.g., COX11, COX15, and MAPK-9) were upregulated by training only in COPD patients. We conclude that both COPD and control subjects demonstrated functional responses to training but with somewhat different patterns in muscle gene expression. The pathways that are uniquely induced by exercise in COPD (e.g., ubiquitin proteasome and COX) might indicate a greater degree of tissue stress (perhaps by altered O(2) and CO(2) dynamics) than in controls.     

Effects of training, exercise and diet on muscle glycolysis and liver gluconeogenesis.

Trained and untrained rats were fed either a control, high-fat, or high-carbohydrate diet and then sacrificed in either a rested or exhausted state. The $\text{in vitro}$ activity of several muscle glycolytic and liver gluconeogenic enzymes was measured. Muscle hexokinase, phosphorylase, and phosphofructokinase activities were increased after training. Hexokinase was decreased in exhausted rats. Phosphorylase and phosphofructokinase were increased in untrained-exhausted rats but were unchanged in trained-exhausted rats. Liver pyruvate carboxylase and phosphoenolpyruvate carboxykinase activities were increased in trained-rested rats fed a high-fat diet. In trained-exhausted rats phosphoenolpyruvate carboxykinase activity was increased regardless of diet fed. Blood glucose was decreased in trained-exhausted rats, but it was increased in untrained-exhausted rats. Plasma glucocorticoid level was increased in exhausted rats. This study showed that training was associated with an increased muscle glycolytic capacity. Training was also related to the ability of liver to increase phosphoenolpyruvate carboxykinase activity during exercise, thereby increasing gluconeogenic capacity.     

Effects of prior exercise and a low-carbohydrate diet on muscle sarcoplasmic reticulum function during cycling in women.

The effects of exercise and diet on sarcoplasmic reticulum Ca(2+)-cycling properties in female vastus lateralis muscle were investigated in two groups of women following four different conditions. The conditions were 4 days of a low-carbohydrate (Lo CHO) and glycogen-depleting exercise plus a Lo CHO diet (Ex + Lo CHO) (experiment 2) and 4 days of normal CHO (Norm CHO) and glycogen-depleting exercise plus Norm CHO (Ex + Norm CHO) (experiment 1). Peak aerobic power (Vo2peak)) was 38.1 +/- 1.4 (SE); n = 9 and 35.6 +/- 1.4 ml.kg(-1).min(-1); n = 9, respectively. Sarcoplasmic reticulum properties measured in vitro in homogenates (micromol.g protein(-1).min(-1)) indicated exercise-induced reductions (P < 0.05) in maximal Ca(2+)-ATPase activity (0 > 30, 60 min > fatigue), Ca(2+) uptake (0 > 30 > 60 min, fatigue), and Ca(2+) release, both phase 1 (0, 30 > 60 min, fatigue) and phase 2 (0 > 30, 60 min, fatigue; 30 min > fatigue) in Norm CHO. Exercise was without effect in altering the Hill slope (n(H)), defined as the slope of relationship between Ca(2+)-ATPase activity and Ca(2+) concentration. No differences were observed between Norm CHO and Ex+Norm CHO. Compared with Norm CHO, Lo CHO resulted in a lower (P < 0.05) Ca(2+) uptake, phase 1 Ca(2+) release (30 min), and n(H). Ex + Lo CHO resulted in a greater (P < 0.05) Ca(2+) uptake and n(H) compared with Lo CHO. The results demonstrate that Lo CHO alone can disrupt SR Ca(2+) cycling and that, with the exception of Ca(2+) release, a glycogen-depleting session of exercise before Lo CHO can reverse the effects.     

Effects of pregnancy and chronic exercise on maternal cardiac structure and function

This study examined the interactive effects of pregnancy and aerobic conditioning on maternal cardiac structure and function. Effects of closely monitored cycle ergometer conditioning were studied during the second (TM2) and third trimesters (TM3) in 22 previously sedentary pregnant women (exercised group, EG) and a nonexercising pregnant control group with similar characteristics (CG, n = 19). Subjects were studied in the resting state by two-dimensional echocardiography and during cycle ergometer exercise at three steady-state power outputs at the start of TM2 (ENTRY), at the end of TM2 and TM3 (postconditioning), and 3-4 months postpartum (NPR, nonpregnant reference, CG only). Aerobic conditioning did not increase left ventricular dimensions beyond those attributable to pregnancy itself. In addition, in contrast with previous studies of nonpregnant women, physical conditioning during pregnancy did not reduce heart rate (HR) in the resting state. During exercise, the slope of the HR versus oxygen uptake (VO2) regression decreased significantly between preconditioning and the end of TM3 in the EG, suggesting that training-induced reductions in HR become more evident with increasing exercise intensity. Also, significant reductions in oxygen pulse (VO2/HR) were observed at all three work rates in the CG, but not in the EG. These findings support the hypothesis that the cardiovascular effects of aerobic conditioning are obscured by more powerful effects of pregnancy in the resting state but become "unmasked" during strenuous exercise.     

Effects of chronic exercise on the kidneys at different ages

In order to determine the effects of chronic exercise on the kidneys at different ages, young, adult, and old rats swam 1 hour either daily or twice a week for 10 weeks and then were killed along with unexercised controls. The kidneys were removed and sections were prepared for histometric analysis including planimetric measurements on camera lucida drawings of renal components and line sampling. With both degrees of exercise young rats showed lower kidney weight, fewer glomeruli and less medullary tissue than unexercised controls. In the adult group no significant differences were noted between exercised and unexercised rats. In old rats both degrees of exercise resulted in a loss of kidney weight and medullary and cortical mass, and a decrease in size of glomeruli while total number of glomeruli remained unchanged. Thus the effects of chronic exercise on the kidneys varied with age. Retarded kidney development occurred in young animals; a loss of renal tissue in old animals; and no change in adult animals.     

Effects of chronic nitric oxide synthase inhibition on responses to acute exercise in swine.

Nitric oxide (NO) is potentially involved in several responses to acute exercise. We tested the hypotheses that inhibition of NO formation reduces maximal O(2) delivery to muscle, but does not affect O(2) utilization by muscle, therefore lowering maximal O(2) consumption. To test these hypotheses, swine (approximately 30 kg) drank either tap water (Con, n = 25) or water with N(G)-nitro-l-arginine methyl ester (8.0 +/- 0.4 mg x kg(-1) x day(-1) for >or=4 wk; LN, n = 24). Treatment efficacy was reflected by higher mean arterial pressure and lower plasma NO metabolite concentration in LN than Con (both P < 0.05). Swine completed two graded treadmill running tests to maximum. In the first test, O(2) consumption was determined at rest through maximal exercise intensity. O(2) consumption did not differ between groups at rest or at most exercise intensities, including maximum (Con, 40.8 +/- 1.8 ml x min(-1) x kg(-1); LN, 40.4 +/- 2.9; not significant). In the second test, tissue-specific blood flows were determined using the radiolabeled-microsphere technique. At rest, blood flows were lower (P < 0.05) in LN compared with Con for a number of tissues, including kidney, adrenal, lung, and several skeletal muscles. During both submaximal and maximal exercise, however, blood flows were similar between Con and LN for all 16 muscles examined; only blood flows to kidney (Con, 99 +/- 16 ml x min(-1) x 100 g; LN, 55 +/- 15; P < 0.05) and pancreas (Con, 25 +/- 7; LN, 6 +/- 2; P < 0.05) were lower in LN at maximum. Endothelium-dependent, but not -independent, relaxation of renal arterial segments was reduced (P < 0.05) in vitro. These data indicate that exercise-induced increases in muscle blood flows are maintained with chronic inhibition of NO formation and that maximal O(2) consumption is therefore preserved. Redundant vasodilatory pathways and/or upregulation of these pathways may underlie these findings.     

Effects of continuous low-carbohydrate diet after long-term exercise on GLUT-4 protein content in rat skeletal muscle.

Stimulation of AMPK and decreased glycogen levels in skeletal muscle have a deep involvement in enhanced insulin action and GLUT-4 protein content after exercise training. The present study examined the chronic effects of a continuous low-carbohydrate diet after long-term exercise on GLUT-4 protein content, glycogen content, AMPK, and insulin signaling in skeletal muscle. Rats were divided randomly into four groups: normal chow diet sedentary (N-Sed), low carbohydrate diet sedentary (L-Sed), normal chow diet exercise (N-Ex), and low carbohydrate diet exercise (L-Ex) groups. Rats in the exercise groups (N-Ex and L-Ex) were exercised by swimming for 6 hours/day in two 3-hour bouts separated by 45 minutes of rest. The 10-day exercise training resulted in a significant increase in the GLUT-4 protein content (p<0.01). Additionally, the GLUT-4 protein content in L-Ex rats was increased by 29% above that in N-Ex rats (p<0.01). Finally, the glycogen content in skeletal muscle of L-Ex rats was decreased compared with that of N-Ex rats. Taken together, we suggest that the maintenance of glycogen depletion after exercise by continuous low carbohydrate diet results in the increment of the GLUT-4 protein content in skeletal muscle.     

Effects of exercise training on alpha-motoneurons.

Evidence is presented that one locus of adaptation in the "neural adaptations to training" is at the level of the alpha-motoneurons. With increased voluntary activity, these neurons show evidence of dendrite restructuring, increased protein synthesis, increased axon transport of proteins, enhanced neuromuscular transmission dynamics, and changes in electrophysiological properties. The latter include hyperpolarization of the resting membrane potential and voltage threshold, increased rate of action potential development, and increased amplitude of the afterhyperpolarization following the action potential. Many of these changes demonstrate intensity-related adaptations and are in the opposite direction under conditions in which chronic activity is reduced. A five-compartment model of rat motoneurons that innervate fast and slow muscle fibers (termed "fast" and "slow" motoneurons in this paper), including 10 active ion conductances, was used to attempt to reproduce exercise training-induced adaptations in electrophysiological properties. The results suggest that adaptations in alpha-motoneurons with exercise training may involve alterations in ion conductances, which may, in turn, include changes in the gene expression of the ion channel subunits, which underlie these conductances. Interestingly, the acute neuromodulatory effects of monoamines on motoneuron properties, which would be a factor during acute exercise as these monoaminergic systems are activated, appear to be in the opposite direction to changes measured in endurance-trained motoneurons that are at rest. It may be that regular increases in motoneuronal excitability during exercise via these monoaminergic systems in fact render the motoneurons less excitable when at rest. More research is required to establish the relationships between exercise training, resting and exercise motoneuron excitability, ion channel modulation, and the effects of neuromodulators.     

Effects of chronic alcoholic disease on magnocellular and parvocellular hypothalamic neurons in men.

Although numerous data showing severe morphological impairment of magnocellular and parvocellular hypothalamic neurons due to chronic alcoholic consumption have been gathered from animal experiments, only one study (Harding et al., 1996) was performed on POST MORTEM human brain. This study showed a reduction in the number of vasopressin (VP)-immunoreactive neurons in the supraoptic (SON) and paraventricular (PVN) nuclei, but did not provide any data regarding the effect of chronic alcohol intake on human parvocellular neurons. In order to assess whether the changes observed in the animal model also occur in humans and provide a structural basis for the results of clinical tests, we performed immunohistochemical and morphometric analysis of magnocellular (VP and oxytocin, OT) and parvocellular (corticotropin-releasing hormone, CRH) neurons in post-mortem brains of patients afflicted with chronic alcoholic disease. We analyzed 26-male alcoholics and 22 age-matched controls divided into two age groups--"young" (< 40 yr) and "old" (> 40 yr). Hypothalamic sections were stained for OT, VP, and CRH. The analysis revealed: 1) decrease in VP-immunoreactivity in the SON and PVN as well as OT-immunoreactivity in the SON in alcoholic patients; 2) increase in OT-immunoreactivity in the PVN; 3) increase in CRH-immunoreactivity in parvocellular neurons in the PVN. Furthermore, the proportion of cells containing CRH and VP was increased in alcoholics. These findings indicate that chronic alcohol consumption does indeed impair the morphology of magnocellular neurons. The enhancement of CRH-immunoreactivity and increased co-production of CRH and VP in parvocellular neurons may be due to a decline in glucocorticoid production, implied by the hypoplasic impairment of adrenal cortex we observed in alcoholics during the course of this study.     

Effects of high-cholesterol diet and parallel exercise training on the vascular function of rabbit aortas: a time course study.

It is plausible to assume that exercise training, when applied early enough, can completely correct atherosclerotic defects. Using rabbit aortic specimens, we examined the effects of chronic exercise and high-cholesterol diet feeding on vascular function for different time periods. Male New Zealand White rabbits were divided into four groups: the normal diet groups with or without exercise training and the high-cholesterol diet groups with or without exercise training. Animals in high-cholesterol diet groups were fed 2% cholesterol rabbit chow for 2, 4, or 6 wk. Those in exercise training groups ran on a treadmill at 0.88 km/h for up to 40 min/day, 5 days/wk for the same period of time as the diet feeding. Thoracic aortas were isolated for functional and immunohistochemical analyses. We found that 1). although high-cholesterol diet feeding (>or=2 wk) elevated serum cholesterol levels and impaired acetylcholine-evoked vasorelaxation, only the latter effect was reversed by exercise training; 2). the effects of diet and exercise on acetylcholine-evoked vasorelaxation were mainly due to altered release of nitric oxide and endothelium-derived hyperpolarizing factor; and 3). diet feeding for 4 or 6 wk caused significant lipid deposition and expression of P-selectin, VCAM-1, monocyte chemoattractant protein-1, and inducible nitric oxide synthase, which were largely reduced by exercise training. In conclusion, parallel exercise training almost completely reverses the early-stage endothelial dysfunction caused by high-cholesterol diet feeding.     

High fat diet aggravates cardiomyopathy in murine chronic Chagas disease

Infection with Trypanosoma cruzi, the etiologic agent in Chagas disease, may result in heart disease. Over the last decades, Chagas disease endemic areas in Latin America have seen a dietary transition from the traditional regional diet to a Western style, fat rich diet. Previously, we demonstrated that during acute infection high fat diet (HFD) protects mice from the consequences of infection-induced myocardial damage through effects on adipogenesis in adipose tissue and reduced cardiac lipidopathy. However, the effect of HFD on the subsequent stages of infection – the indeterminate and chronic stages – has not been investigated. To address this gap in knowledge, we studied the effect of HFD during indeterminate and chronic stages of Chagas disease in the mouse model. We report, for the first time, the effect of HFD on myocardial inflammation, vasculopathy, and other types of dysfunction observed during chronic T. cruzi infection. Our results show that HFD perturbs lipid metabolism and induces oxidative stress to exacerbate late chronic Chagas disease cardiac pathology.     

Effects of a 24-h carbohydrate-poor diet on metabolic and hormonal responses during prolonged glucose-infused leg exercise

Extant literature dealing with metabolic and hormonal adaptations to exercise following carbohydrate (CHO) reduced diets is not sufficiently precise to allow researchers to partial out the effects of reduced blood glucose levels from other general effects produced by low CHO diets. In order to shed light on this issue, a study was conducted to examine the effects of a 24-h CHO-poor diet on substrate and endocrine responses during prolonged (75 min; 60% Vo2max) glucose-infused leg exercise. Eight subjects exercised on a cycle ergometer in the two following conditions: 1) after a normal diet (CHON), and 2) after a 24-h low CHO diet (CHOL). In both conditions, glucose was constantly infused intravenously (2.2 mg . kg-1 . min-1) from the 10th to the 75th min of exercise in relatively small amounts (10.4 +/- 0.8 g). No significant differences in blood glucose concentrations were found between the two conditions at rest and during exercise although a significant increase (p less than 0.01) in glucose level was observed in both conditions after 40 min of exercise. The CHOL as compared to the CHON condition, was associated with significantly (p less than 0.05) lower resting concentrations of insulin, muscle glycogen (8.7 vs 10.6 g . kg-1), and triacylglycerol, and greater concentrations of beta-hydroxybutyrate (0.5 vs 0.2 mmol . L-1), and free fatty acids. During exercise, the CHOL condition as compared to the CHON condition, was associated with significantly (p less than 0.05) lower insulin and R values, as well as greater free fatty acid (from min 20 to 60) and epinephrine (min 60 to 75) concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Invited review: Effects of acute exercise and exercise training on insulin resistance.

Insulin resistance of skeletal muscle glucose transport is a key defect in the development of impaired glucose tolerance and Type 2 diabetes. It is well established that both an acute bout of exercise and chronic endurance exercise training can have beneficial effects on insulin action in insulin-resistant states. This review summarizes the present state of knowledge regarding these effects in the obese Zucker rat, a widely used rodent model of obesity-associated insulin resistance, and in insulin-resistant humans with impaired glucose tolerance or Type 2 diabetes. A single bout of prolonged aerobic exercise (30-60 min at approximately 60-70% of maximal oxygen consumption) can significantly lower plasma glucose levels, owing to normal contraction-induced stimulation of GLUT-4 glucose transporter translocation and glucose transport activity in insulin-resistant skeletal muscle. However, little is currently known about the effects of acute exercise on muscle insulin signaling in the postexercise state in insulin-resistant individuals. A well-established adaptive response to exercise training in conditions of insulin resistance is improved glucose tolerance and enhanced skeletal muscle insulin sensitivity of glucose transport. This training-induced enhancement of insulin action is associated with upregulation of specific components of the glucose transport system in insulin-resistant muscle and includes increased protein expression of GLUT-4 and insulin receptor substrate-1. It is clear that further investigations are needed to further elucidate the specific molecular mechanisms underlying the beneficial effects of acute exercise and exercise training on the glucose transport system in insulin-resistant mammalian skeletal muscle.     

Effects of atherogenic diet on young farm pigs.

This study was designed to assess the usefulness of young farm pigs as an experimental model for hypercholesterolemia. In order to test this, we investigated both serologic and electrocardiographic effects of atherogenic diet. Four-week-old pigs were fed an atherogenic diet for 8 weeks. No arrhythmia was observed on ECG in all animals. There were no significant difference between control and atherogenic diet group on the values of ECG parameters. However, plasma lipids values of atherogenic diet group were significantly (p less than 0.05) higher than those of control diet group. Thus, hypercholesterolemia was induced in young farm pigs by feeding atherogenic diet in a relatively short time. This fact suggests that young farm pigs may be an useful model for further studies of the effect of hypercholesterolemia on cardiovascular function and the early pathogenesis of atherosclerosis.