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 exercise training on papain-induced pulmonary emphysema in Wistar rats.

The purpose of the present study was to evaluate the role of exercise training on the development of papain-induced emphysema in rats. Our hypothesis was that the increase in pulmonary tissue stretching associated with exercise could increase the severity of a protease-induced emphysema. Wistar rats were randomly assigned to four groups (n = 10 for each group) that received, respectively, intratracheal infusion of papain (6 mg in 1 ml of 0.9% NaCl) or vehicle and were submitted or not to a protocol of exercise on a treadmill. Rats exercised at 13.3 m/min, 6 days/wk, for 9 wk (increasing exercise time, from 10 to 35 min). We measured respiratory system elastance and resistance, the size and weight of the heart, and pulmonary mean linear intercept (Lm). After 9 wk of exercise training, there were no differences in respiratory system resistance and elastance values among the four experimental groups. Volume of the heart was significantly greater in rats submitted to exercise training (P = 0.007) compared with sedentary rats due to increases in volumes of both right and left cardiac chambers. Lm was significantly greater in rats that received papain compared with saline-infused rats (P = 0.025). Surprisingly, this was true, even though there was no significant decrease in elastance, possibly due to connective tissue remodeling. However, Lm was significantly greater in papain + exercise rats compared with rats that received papain and were not submitted to exercise. We conclude that exercise training can increase alveolar damage induced by papain infusion.     

Effects of exercise training on airway closure in asthmatics

We previously reported that responsiveness to methacholine (Mch) in the absence of deep inspiration (DI) decreased in healthy subjects after a short course of exercise training. We assessed whether a similar beneficial effect of exercise on airway responsiveness could occur in asthmatics. Nine patients (male/female: 3/6; mean age ± SD: 24 ± 2 yr) with mild untreated asthma [forced expiratory volume in 1 s (FEV(1)): 100 ± 7.4% pred; FEV(1)/vital capacity (VC): 90 ± 6.5%] underwent a series of single-dose Mch bronchoprovocations in the absence of DI in the course of a 10-wk training rowing program (6 h/wk of submaximal and maximal exercise), at baseline (week 0), and at week 5 and 10. The single-dose Mch was established as the dose able to induce ≥15% reduction in inspiratory vital capacity (IVC) and was administered to each subject at every challenge occasion. Five asthmatics (male/female: 1/4; mean age ± SD: 26 ± 3 yr) with similar baseline lung function (FEV(1): 102 ± 7.0% predicted; FEV(1)/VC: 83 ± 6.0%; P = 0.57 and P = 0.06, respectively) not participating in the exercise training program served as controls. In the trained group, the Mch-induced reduction in IVC from baseline was 22 ± 10% at week 0, 13 ± 11% at week 5 (P = 0.03), and 11 ± 8% at week 10 (P = 0.028). The Mch-induced reduction in FEV(1) did not change with exercise (P = 0.69). The reduction in responsiveness induced by exercise was of the same magnitude of that previously obtained in healthy subjects (50% with respect to pretraining). Conversely, Mch-induced reduction in IVC in controls remained unchanged after 10 wk (%reduction IVC at baseline: 21 ± 20%; after 10 wk: 29 ± 14%; P = 0.28). This study indicates that a short course of physical training is capable of reducing airway responsiveness in mild asthmatics.     

Effects of exercise training on acclimatization to hypoxia: systemic O2 transport during maximal exercise.

Acclimatization to hypoxia has minimal effect on maximal O2 uptake (Vo2 max). Prolonged hypoxia shows reductions in cardiac output (Q), maximal heart rate (HR-max), myocardial beta-adrenoceptor (beta-AR) density, and chronotropic response to isoproterenol. This study tested the hypothesis that exercise training (ET), which attenuates beta-AR downregulation, would increase HRmax and Q of acclimatization and result in higher Vo2 max. After 3 wk of ET, rats lived at an inspired Po2 of 70 Torr for 10 days (acclimatized trained rats) or remained in normoxia, while both groups continued to train in normoxia. Controls were sedentary acclimatized and nonacclimatized rats. All rats exercised maximally in normoxia and hypoxia (inspired Po2 of 70 Torr). Myocardial beta-AR density and the chronotropic response to isoproterenol were reduced, and myocardial cholinergic receptor density was increased after acclimatization; all of these receptor changes were reversed by ET. Normoxic Vo2 max (in ml.min-1.kg-1) was 95.8 +/- 1.0 in acclimatized trained (n = 6), 87.7 +/- 1.7 in nonacclimatized trained (P < 0.05, n = 6), 74.2 +/- 1.4 in acclimatized sedentary (n = 6, P < 0.05), and 72.5 +/- 1.2 in nonacclimatized sedentary (n = 8; P > 0.05 acclimatized sedentary vs. nonacclimatized sedentary). A similar distribution of Vo2 max values occurred in hypoxic exercise. Q was highest in trained acclimatized and nonacclimatized, intermediate in nonacclimatized sedentary, and lowest in acclimatized sedentary groups. ET preserved Q in acclimatized rats thanks to maintenance of HRmax as well as of maximal stroke volume. Q preservation, coupled with a higher arterial O2 content, resulted in the acclimatized trained rats having the highest convective O2 transport and Vo2 max. These results show that ET attenuates beta-AR downregulation and preserves Q and Vo2 max after acclimatization, and support the idea that beta-AR downregulation partially contributes to the limitation of Vo2 max after acclimatization in rats.     

Effects of exercise training on contractile function in myocardial trabeculae after ischemia-reperfusion.

Potential protective effects of aerobic exercise training on the myocardium, before an ischemic event, are not completely understood. The purpose of the study was to investigate the effects of exercise training on contractile function after ischemia-reperfusion (Langendorff preparation with 15-min global ischemia/30-min reperfusion). Trabeculae were isolated from the left ventricles of both sedentary control and 10- to 12-wk treadmill exercise-trained rats. The maximal normalized isometric force (force/cross-sectional area; Po/CSA) and shortening velocity (Vo) in isolated, skinned ventricular trabeculae were measured using the slack test. Ischemia-reperfusion induced significant contractile dysfunction in hearts from both sedentary and trained animals; left ventricular developed pressure (LVDP) and maximal rates of pressure development and relaxation (+/-dP/dtmax) decreased, whereas end-diastolic pressure (EDP) increased. However, this dysfunction (as expressed as percent change from the last 5 min before ischemia) was attenuated in trained myocardium [LVDP: sedentary -60.8 +/- 6.4% (32.0 +/- 5.5 mmHg) vs. trained -15.6 +/- 8.6% (64.9 +/- 6.6 mmHg); +dP/dtmax: sedentary -54.1 +/- 4.7% (1,058.7 +/- 124.2 mmHg/s) vs. trained -16.7 +/- 8.4% (1,931.9 +/- 188.3 mmHg/s); -dP/dtmax: sedentary -44.4 +/- 2.5% (-829.3 +/- 52.0 mmHg/s) vs. trained -17.9 +/- 7.2% (-1,341.3 +/- 142.8 mmHg/s); EDP: sedentary 539.5 +/- 147.6%; (41.3 +/- 6.0 mmHg) vs. trained 71.6 +/- 30.6%; 11.4 +/- 1.2 mmHg]. There was an average 26% increase in Po/CSA in trained trabeculae compared with sedentary controls, and this increase was not affected by ischemia-reperfusion. Ischemia-reperfusion reduced Vo by 39% in both control and trained trabeculae. The relative amount of the beta-isoform of myosin heavy chain (MHC-beta) was twofold greater in trained trabeculae as well as in the ventricular free walls. Despite a possible increase in the economy in the trained heart, presumed from a greater amount of MHC-beta, ischemia-reperfusion reduced Vo, to a similar extent in both control and trained animals. Nevertheless, the trained myocardium appears to have a greater maximum force-generating ability that may, at least partially, compensate for reduced contractile function induced by a brief period of ischemia.     

Effects of body temperature during exercise training on myocardial adaptations

This study determined the role of body temperature during chronic exercise on myocardial stress proteins and antioxidant enzymes as well as functional recovery after an ischemic insult. Male Sprague-Dawley rats were exercised for 3, 6, or 9 wk in a 23 degrees C room (3WK, 6WK, and 9WK, respectively) or in a 4-8 degrees C environment with wetted fur (3WKC, 6WKC, and 9WKC, respectively). The colder room prevented elevations in core temperature. During weeks 3-9 the animals ran 5 days/wk up a 6% grade at 20 m/min for 60 min. Myocardial heat shock protein 70 (HSP 70) increased 12.3-fold (P < 0.05) in 9WK versus sedentary (SED) rats but was unchanged in the cold-room runners. Compared with SED rats, alphaB-crystallin was 90% higher in 9WKC animals, HSP 90 was 50% higher in 3WKC and 6WKC animals, and catalase was 23% higher in 3WK animals (P < 0.05 for all). Cytosolic superoxide dismutase increased and mitochondrial SOD decreased (P < 0.05) in 3WK and 6WK rats compared with 3WKC and 6WKC rats. Antioxidant enzymes returned to SED values in all runners by 9 wk. No differences were observed among any of the groups for glucose-regulated protein 75, heme oxygenase-1, or glutathione peroxidase. Mechanical recovery of isolated working hearts after 22.5 min of global ischemia was enhanced in 9WK (P < 0.05) but not in 9WKC rats. We conclude that exercise training results in dynamic changes in cardioprotective proteins over time which are influenced by core temperature. In addition, cardioprotection resulting from chronic exercise appears to be due to increased HSP 70.     

Effects of exercise training on thermoregulatory responses and blood volume in older men.

We assessed the effects of aerobic and/or resistance training on thermoregulatory responses in older men and analyzed the results in relation to the changes in peak oxygen consumption rate (VO(2 peak)) and blood volume (BV). Twenty-three older men [age, 64 +/- 1 (SE) yr; VO(2 peak), 32.7 +/- 1.1 ml. kg(-1). min(-1)] were divided into three training regimens for 18 wk: control (C; n = 7), aerobic training (AT; n = 8), and resistance training (RT; n = 8). Subjects in C were allowed to perform walking of ~10,000 steps/day, 6-7 days/wk. Subjects in AT exercised on a cycle ergometer at 50-80% VO(2 peak) for 60 min/day, 3 days/wk, in addition to the walking. Subjects in RT performed a resistance exercise, including knee extension and flexion at 60-80% of one repetition maximum, two to three sets of eight repetitions per day, 3 days/wk, in addition to the walking. After 18 wk of training, VO(2 peak) increased by 5.2 +/- 3.4% in C (P > 0.07), 20.0 +/- 2.5% in AT (P < 0.0001), and 9.7 +/- 5.1% in RT (P < 0.003), but BV remained unchanged in all trials. In addition, the esophageal temperature (T(es)) thresholds for forearm skin vasodilation and sweating, determined during 30-min exercise of 60% VO(2 peak) at 30 degrees C, decreased in AT (P < 0.02) and RT (P < 0.02) but not in C (P > 0.2). In contrast, the slopes of forearm skin vascular conductance/T(es) and sweat rate/T(es) remained unchanged in all trials, but both increased in subjects with increased BV irrespective of trials with significant correlations between the changes in the slopes and BV (P < 0.005 and P < 0.0005, respectively). Thus aerobic and/or resistance training in older men increased VO(2 peak) and lowered T(es) thresholds for forearm skin vasodilation and sweating but did not increase BV. Furthermore, the sensitivity of the increase in skin vasodilation and sweating at a given increase in T(es) was more associated with BV than with VO(2 peak).     

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 intense exercise training on plasma catecholamines in coronary patients

This paper reports the effect of 12 mo of intense endurance exercise training on the plasma catecholamine response to exercise in 11 male patients [aged 50 +/- 8 yr (mean +/- SD)] with coronary artery disease. A substantial adaptation to training was attained as evidenced by a 42% increase in maximum O2 uptake capacity. At rest, heart rate was lower after training, but resting blood pressure and plasma catecholamines were unchanged. At the same absolute work rate, plasma norepinephrine and epinephrine levels, rate pressure product, and ischemic S-T segment depression were all significantly lower after training. A higher plasma norepinephrine level was attained at maximal exercise after training (2,049 +/- 654 before vs. 3,408 +/- 1,454 pg/ml after, P less than 0.025); this was associated with a higher systolic blood pressure (175 +/- 25 before vs. 188 +/- 22 mmHg after, P less than 0.025) and a higher rate-pressure product (25.3 X 10(3) +/- 4.5 X 10(3) before vs. 27.6 X 10(3) +/- 5.2 X 10(3) after, P less than 0.025). Despite the higher plasma norepinephrine level and rate pressure product, S-T segment depression at maximal exercise was unchanged. These findings suggest that some patients with coronary arterial disease can attain a higher myocardial O2 requirement, without electrocardiographic evidence of increased ischemia, after prolonged strenuous exercise training.     

Effects of fasting and training on pyruvate dehydrogenase activation during exercise

1. The effect of exercise (2 hr treadmill running at 28 m/min) on PDHa (the activity of the active form of pyruvate dehydrogenase) in untrained rats, trained rats (2 hr/d at 25 m/min for 4 wk), and in 24 hr fasted rats was determined. 2. Exercise increased PDHa activity approximately 2 fold in fed-untrained rats. 3. Fasting decreased PDHa activity in sedentary rats to approximately half the activity in fed rats. 4. The increase in PDHa activity during exercise was less in fasted than fed rats. 5. Training did not change the total activity of PDH (phosphorylated plus nonphosphorylated forms) but the percent of PDH in the active form was increased in muscle of trained-rested rats. 6. PDHa activity was unchanged by acute exercise (2.5 hr at 40 m/min) in the trained rats.     

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 exercise training on coronary collateralization and control of collateral resistance

Coronary collateral vessels serve as a natural protective mechanism to provide coronary flow to ischemic myocardium secondary to critical coronary artery stenosis. The innate collateral circulation of the normal human heart is typically minimal and considerable variability occurs in extent of collateralization in coronary artery disease patients. A well-developed collateral circulation has been documented to exert protective effects upon myocardial perfusion, contractile function, infarct size, and electrocardiographic abnormalities. Thus therapeutic augmentation of collateral vessel development and/or functional adaptations in collateral and collateral-dependent arteries to reduce resistance into the ischemic myocardium represent a desirable goal in the management of coronary artery disease. Tremendous evidence has provided documentation for the therapeutic benefits of exercise training programs in patients with coronary artery disease (and collateralization); mechanisms that underlie these benefits are numerous and multifaceted, and currently under investigation in multiple laboratories worldwide. The role of enhanced collateralization as a major beneficial contributor has not been fully resolved. This topical review highlights literature that examines the effects of exercise training on collateralization in the diseased heart, as well as effects of exercise training on vascular endothelial and smooth muscle control of regional coronary tone in the collateralized heart. Future directions for research in this area involve further delineation of cellular/molecular mechanisms involved in effects of exercise training on collateralized myocardium, as well as development of novel therapies based on emerging concepts regarding exercise training and coronary artery disease.     

Effects of intensity and duration of exercise on muscular responses to training of thoroughbred racehorses.

This study examined the effects of the intensity and duration of exercise on the nature and magnitude of training adaptations in muscle of adolescent (2-3 yr old) racehorses. Six thoroughbreds that had been pretrained for 2 mo performed six consecutive conditioning programs of varying lactate-guided intensities [velocities eliciting blood lactate concentrations of 2.5 mmol/l (v2.5) and 4 mmol/l (v4), respectively] and durations (5, 15, 25 min). Pre- and posttraining gluteus muscle biopsies were analyzed for myosin heavy chain content, fiber-type composition, fiber size, capillarization, and fiber histochemical oxidative and glycolytic capabilities. Although training adaptations were similar in nature, they varied greatly in magnitude among the different training protocols. Overall, the use of v4 as the exercise intensity for 25 min elicited the most consistent training adaptations in muscle, whereas the minimal training stimulus that evoked any significant change was identified with exercises of 15 min at v2.5. Within this range, muscular adaptations showed significant trends to be proportional to the exercise load of specific training programs. Taken together, these data suggest that muscular adaptations to training in horses occur on a continuum that is based on the exercise intensity and duration of training. The practical implications of this study are that exercises for 15 to 25 min/day at velocities between v2.5 and v4 can improve in the short term (3 wk) the muscular stamina in thoroughbreds. However, exercises of 5-15 min at v4 are necessary to enhance muscular features related to strength (hypertrophy).     

Effects of endurance exercise training on markers of cholesterol absorption and synthesis

Abnormal cholesterol metabolism, including low intestinal cholesterol absorption and elevated synthesis, is prevalent in diabetes, obesity, hyperlipidemia, and the metabolic syndrome. Diet-induced weight loss improves cholesterol absorption in these populations, but it is not known if endurance exercise training also improves cholesterol homeostasis. To examine this, we measured circulating levels of campesterol, sitosterol, and lathosterol in 65 sedentary subjects (average age 59 years; with at least one metabolic syndrome risk factor) before and after 6 months of endurance exercise training. Campesterol and sitosterol are plant sterols that correlate with intestinal cholesterol absorption, while lathosterol is a marker of whole body cholesterol synthesis. Following the intervention, plant sterol levels were increased by 10% (p<0.05), but there was no change in plasma lathosterol. In addition, total and LDL-cholesterol were reduced by 0.16 mmol and 0.10 mmol, respectively (p<0.05), while HDL-C levels increased by 0.09 mmol (p<0.05). Furthermore, the change in plant sterols was positively correlated with the change in VO2max (r=0.310, p=0.004), independent of other metabolic syndrome risk factors. These data indicate that exercise training reduces plasma cholesterol despite increasing cholesterol absorption in subjects with metabolic syndrome risk factors.     

Effects of 7 wk of endurance training on human skeletal muscle metabolism during submaximal exercise.

This is the first study to examine the effects of endurance training on the activation state of glycogen phosphorylase (Phos) and pyruvate dehydrogenase (PDH) in human skeletal muscle during exercise. We hypothesized that 7 wk of endurance training (Tr) would result in a posttransformationally regulated decrease in flux through Phos and an attenuated activation of PDH during exercise due to alterations in key allosteric modulators of these important enzymes. Eight healthy men (22 +/- 1 yr) cycled to exhaustion at the same absolute workload (206 +/- 5 W; approximately 80% of initial maximal oxygen uptake) before and after Tr. Muscle biopsies (vastus lateralis) were obtained at rest and after 5 and 15 min of exercise. Fifteen minutes of exercise post-Tr resulted in an attenuated activation of PDH (pre-Tr: 3.75 +/- 0.48 vs. post-Tr: 2.65 +/- 0.38 mmol.min(-1).kg wet wt(-1)), possibly due in part to lower pyruvate content (pre-Tr: 0.94 +/- 0.14 vs. post-Tr: 0.46 +/- 0.03 mmol/kg dry wt). The decreased pyruvate availability during exercise post-Tr may be due to a decreased muscle glycogenolytic rate (pre-Tr: 13.22 +/- 1.01 vs. post-Tr: 7.36 +/- 1.26 mmol.min(-1).kg dry wt(-1)). Decreased glycogenolysis was likely mediated, in part, by posttransformational regulation of Phos, as evidenced by smaller net increases in calculated muscle free ADP (pre-Tr: 111 +/- 16 vs. post-Tr: 84 +/- 10 micromol/kg dry wt) and P(i) (pre-Tr: 57.1 +/- 7.9 vs. post-Tr: 28.6 +/- 5.6 mmol/kg dry wt). We have demonstrated for the first time that several signals act to coordinately regulate Phos and PDH, and thus carbohydrate metabolism, in human skeletal muscle after 7 wk of endurance training.     

Effects of exercise training on the vascular reactivity of the whole kidney circulation in rabbits.

Exercise training is known to improve vasodilating mechanisms mediated by endothelium-dependent relaxing factors in the cardiac and skeletal muscle vascular beds. However, the effects of exercise training on visceral vascular reactivity, including the renal circulation, are still unclear. We used the experimental model of the isolated perfused rabbit kidney, which involves both the renal macro- and microcirculation, to test the hypothesis that exercise training improves vasodilator mechanisms in the entire renal circulation. New Zealand White rabbits were pen confined (Sed; n = 24) or treadmill trained (0% grade) for 5 days/wk at a speed of 18 m/min during 60 min over a 12-wk period (ExT; n = 24). Kidneys isolated from Sed and ExT rabbits were continuously perfused in a nonrecirculating system under conditions of constant flow and precontracted with norepinephrine (NE). We assessed the effects of exercise training on renal vascular reactivity using endothelial-dependent [acetylcholine (ACh) and bradykinin (BK)] and -independent [sodium nitroprusside (SNP)] vasodilators. ACh induced marked and dose-related vasodilator responses in kidneys from Sed rabbits, the reduction in perfusion pressure reaching 41 +/- 8% (n = 6; P < 0.05). In the kidneys from ExT rabbits, vasodilation induced by ACh was significantly enhanced to 54 +/- 6% (n = 6; P < 0.05). In contrast, BK-induced renal vasodilation was not enhanced by training [19 +/- 8 and 13 +/- 4% reduction in perfusion pressure for Sed and ExT rabbits, respectively (n = 6; P > 0.05)]. Continuous perfusion of isolated kidneys from ExT animals with N(omega)-nitro-L-arginine methyl ester (L-NAME; 300 microM), an inhibitor of nitric oxide (NO) biosynthesis, completely blunted the additional vasodilation elicited by ACh [reduction in perfusion pressure of 54 +/- 6 and 38 +/- 5% for ExT and L-NAME + ExT, respectively (n = 6; P < 0.05)]. On the other hand, L-NAME infusion did not affect ACh-induced vasodilation in Sed animals. Exercise training also increased renal vasodilation induced by SNP [36 +/- 7 and 45 +/- 10% reduction in perfusion pressure for Sed and ExT rabbits, respectively (n = 6; P < 0.05)]. It is concluded that exercise training alters the rabbit kidney vascular reactivity, enhancing endothelium-dependent and -independent renal vasodilation. This effect seems to be related not only to an increased bioavailability of NO but also to the enhanced responsiveness of the renal vascular smooth muscle to NO.     

Effects of exercise training and diabetes on cardiac myosin heavy chain composition

This study determined whether the beneficial effects of exercise training on the diabetic heart previously observed are associated with alterations in ventricular myosin heavy chain (MHC) isoform composition. Diabetes was induced in rats by i.v. streptozotocin. Trained rats were run on a treadmill for 60 min/day, 27 m/min, 10% grade. After 10 wks, ventricular MHC isoenzyme protein composition was analyzed for MHC composition using gel electrophoresis. -MHC and -MHC mRNA were determined by Northern and slot blot hybridization techniques. Both protein and mRNA analyses indicated that sedentary control rats exhibited a predominance of -MHC. Sedentary diabetics exhibited a shift to -MHC. Exercise trained diabetic rats showed a predominance of -MHC. The results indicate that treadmill exercise training of diabetic rat does not prevent the diabetes-induced shift in MHC composition towards the -MHC isoform, thus it is unlikely that the beneficial effects of exercise training on the diabetic heart, previously shown, are due to a normalization of the myosin isoform composition.     

Effects of exercise training and antioxidant R-ALA on glucose transport in insulin-sensitive rat skeletal muscle.

We have recently demonstrated (Saengsirisuwan V, Kinnick TR, Schmit MB, and Henriksen EJ, J Appl Physiol 91: 145-153, 2001) that exercise training (ET) and the antioxidant R-(+)-alpha-lipoic acid (R-ALA) interact in an additive fashion to improve insulin action in insulin-resistant obese Zucker (fa/fa) rats. The purpose of the present study was to assess the interactions of ET and R-ALA on insulin action and oxidative stress in a model of normal insulin sensitivity, the lean Zucker (fa/-) rat. For 6 wk, animals either remained sedentary, received R-ALA (30 mg. kg body wt(-1). day(-1)), performed ET (treadmill running), or underwent both R-ALA treatment and ET. ET alone or in combination with R-ALA significantly increased (P < 0.05) peak oxygen consumption (28-31%) and maximum run time (52-63%). During an oral glucose tolerance test, ET alone or in combination with R-ALA resulted in a significant lowering of the glucose response (17-36%) at 15 min relative to R-ALA alone and of the insulin response (19-36%) at 15 min compared with sedentary controls. Insulin-mediated glucose transport activity was increased by ET alone in isolated epitrochlearis (30%) and soleus (50%) muscles, and this was associated with increased GLUT-4 protein levels. Insulin action was not improved by R-ALA alone, and ET-associated improvements in these variables were not further enhanced with combined ET and R-ALA. Although ET and R-ALA caused reductions in soleus protein carbonyls (an index of oxidative stress), these alterations were not significantly correlated with insulin-mediated soleus glucose transport. These results indicate that the beneficial interactive effects of ET and R-ALA on skeletal muscle insulin action observed previously in insulin-resistant obese Zucker rats are not apparent in insulin-sensitive lean Zucker rats.     

Effects of sprint training on extrarenal potassium regulation with intense exercise in Type 1 diabetes.

Effects of sprint training on plasma K+ concentration ([K+]) regulation during intense exercise and on muscle Na+-K+-ATPase were investigated in subjects with Type 1 diabetes mellitus (T1D) under real-life conditions and in nondiabetic subjects (CON). Eight subjects with T1D and seven CON undertook 7 wk of sprint cycling training. Before training, subjects cycled to exhaustion at 130% peak O2 uptake. After training, identical work was performed. Arterialized venous blood was drawn at rest, during exercise, and at recovery and analyzed for plasma glucose, [K+], Na+ concentration ([Na+]), catecholamines, insulin, and glucagon. A vastus lateralis biopsy was obtained before and after training and assayed for Na+-K+-ATPase content ([3H]ouabain binding). Pretraining, Na+-K+-ATPase content and the rise in plasma [K+] ([K+]) during maximal exercise were similar in T1D and CON. However, after 60 min of recovery in T1D, plasma [K+], glucose, and glucagon/insulin were higher and plasma [Na+] was lower than in CON. Training increased Na+-K+-ATPase content and reduced [K+] in both groups (P < 0.05). These variables were correlated in CON (r = -0.65, P < 0.05) but not in T1D. This study showed first that mildly hypoinsulinemic subjects with T1D can safely undertake intense exercise with respect to K+ regulation; however, elevated [K+] will ensue in recovery unless insulin is administered. Second, sprint training improved K+ regulation during intense exercise in both T1D and CON groups; however, the lack of correlation between plasma delta[K+] and Na+-K+-ATPase content in T1D may indicate different relative contributions of K+-regulatory mechanisms.