Collagen gene expression in rat left ventricle: interactive effect of age and exercise training.

Whether or not exercise training of sufficient intensity and duration to produce left ventricle (LV) hypertrophy also regulates deposition of interstitial collagen and cross-linking at the pretranslational level is unknown. Therefore, the effects of exercise training on gene expression for the two principal fibrillar collagens in LV, types I and III, were assessed in young adult (5 mo), middle-aged (15 mo), and old (26 mo) rats. We also evaluated the potential interaction of changes in mRNA for these procollagens with alterations in LV extracellular matrix characteristics by simultaneously measuring collagen concentration (hydroxyproline) and extent of mature collagen cross-linking (hydroxylysylpyridinoline, HP). Ten weeks of treadmill running resulted in LV hypertrophy and an increased maximal oxygen uptake in all three age groups of trained rats compared with sedentary controls. Percent collagen in rat LV almost doubled (P < 0.0001) from 5 to 26 mo of age, an increase unaffected by exercise training. With aging, a significant decline in expression of mRNAs for both collagen type I (P < 0.005) and type III (P < 0.001) was observed in LV free wall (LVF) but not septum (LVS). Training prevented this decline in LVF mRNAs for the two principal fibrillar collagens in middle-aged rats whereas it attenuated the decline in senescent animals. HP concentration increased significantly with aging in both LVF (P < 0.005) and LVS (P < 0.01). Training modulated this effect, but again only in LVF, so that HP was significantly lower (P < 0.05) in this region of the LV in old trained rats compared with sedentary counterparts. We conclude that exercise training modulates the effects of aging on collagen gene mRNAs and HP cross-linking regionally within the LV.     

The effect of running, strength, and vibration strength training on the mechanical, morphological, and biochemical properties of the Achilles tendon in rats.

Compared with muscle or bone, there is a lack of information about the relationship between tendon adaptation and the applied loading characteristic. The purpose of the present study was to analyze the effect of different exercise modes characterized by very distinct loading patterns on the mechanical, morphological, and biochemical properties of the Achilles tendon. Sixty-four female Sprague-Dawley rats were divided into five groups: nonactive age-matched control (AMC; n = 20), voluntary wheel running (RT; n = 20), vibration strength-trained (LVST; n = 12), high-vibration strength-trained (HVST; n = 6), and high strength-trained (HST; n = 6) group. After a 12-wk-long experimental period, the Achilles tendon was tested mechanically and the cross-sectional area, the soleus and gastrocnemius muscle mass, and mRNA concentration of collagen I, collagen III, tissue inhibitor of metalloproteinase-1 (TIMP-1), transforming growth factor-beta, connective tissue growth factor, and matrix metalloproteinase-2 was determined. Neither in the LVST nor in the HVST group could any adaptation of the Achilles tendon be detected, although the training had an effect on the gastrocnemius muscle mass in the LVST group (P < 0.05). In the HST group, the highest creep was found, but the effect was more pronounced compared with the LVST group (P < 0.05) than with the AMC group. That indicates that this was rather induced by the low muscle mass rather than by training. However, the RT group had a higher TIMP-1 mRNA concentration in the Achilles tendon in contrast to AMC group (P < 0.05), which suggests that this exercise mode may have an influence on tendon adaptation.     

Impact of sex and chronic resistance training on human patellar tendon dry mass, collagen content, and collagen cross-linking

Collagen content and cross-linking are believed to be major determinants of tendon structural integrity and function. Sex and chronic resistance training have been shown to alter tendon function and may also alter the key structural features of tendon. Patellar tendon biopsies were taken from untrained men [n = 8, 1 repetition maximum (RM) = 53 +/- 3 kg], untrained women (n = 8, 1 RM = 29 +/- 2 kg), and resistance-trained (10 +/- 1 yr of training) men (n = 8, 1 RM = 71 +/- 6 kg). Biopsies were analyzed for dry mass, collagen content, and collagen cross-linking (hydroxylysylpyridinoline). We hypothesized that these elements of tendon structure would be lower in women than men, whereas chronic resistance training would increase these parameters in men. Tendon dry mass was significantly lower in women than men (343 +/- 5 vs. 376 +/- 8 microg dry mass/mg tendon wet wt, P < 0.01) and was not influenced by chronic resistance training (P > 0.05). The lower tendon dry mass in women tended to reduce (P = 0.08) collagen content per tendon wet weight. Collagen content of the tendon dry mass was not influenced by sex or resistance training (P > 0.05). Similarly, cross-linking of collagen was unaltered (P > 0.05) by sex or training. Although sex alters the water content of patellar tendon tissue, any changes in tendon function with sex or chronic resistance training in men do not appear to be explained by alterations in collagen content or cross-linking of collagen within the dry mass component of the tendon.     

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.     

Conditioning of the Achilles tendon via ankle exercise improves correlations between sonographic measures of tendon thickness and body anthropometry

Although conditioning is routinely used in mechanical tests of tendon in vitro, previous in vivo research evaluating the influence of body anthropometry on Achilles tendon thickness has not considered its potential effects on tendon structure. This study evaluated the relationship between Achilles tendon thickness and body anthropometry in healthy adults both before and after resistive ankle plantarflexion exercise. A convenience sample of 30 healthy male adults underwent sonographic examination of the Achilles tendon in addition to standard anthropometric measures of stature and body weight. A 10-5 MHz linear array transducer was used to acquire longitudinal sonograms of the Achilles tendon, 20 mm proximal to the tendon insertion. Participants then completed a series (90-100 repetitions) of conditioning exercises against an effective resistance between 100% and 150% body weight. Longitudinal sonograms were repeated immediately on completion of the exercise intervention, and anteroposterior Achilles tendon thickness was determined. Achilles tendon thickness was significantly reduced immediately following conditioning exercise (t = 9.71, P < 0.001), resulting in an average transverse strain of -18.8%. In contrast to preexercise measures, Achilles tendon thickness was significantly correlated with body weight (r = 0.72, P < 0.001) and to a lesser extent height (r = 0.45, P = 0.01) and body mass index (r = 0.63, P < 0.001) after exercise. Conditioning of the Achilles tendon via resistive ankle exercises induces alterations in tendon structure that substantially improve correlations between Achilles tendon thickness and body anthropometry. It is recommended that conditioning exercises, which standardize the load history of tendon, are employed before measurements of sonographic tendon thickness in vivo.     

Cross-Linking in Collagen by Nonenzymatic Glycation Increases the Matrix Stiffness in Rabbit Achilles Tendon

Nonenzymatic glycation of connective tissue matrix proteins is a major contributor to the pathology of diabetes and aging. Previously the author and colleagues have shown that nonenzymatic glycation significantly enhances the matrix stability in the Achilles tendon (Reddy et al., 2002, Arch. Biochem. Biophys., 399, 174–180). The present study was designed to gain further insight into glycation-induced collagen cross-linking and its relationship to matrix stiffness in the rabbit Achilles tendon. The glycation process was initiated by incubating the Achilles tendons (n = 6) in phosphate-buffered saline containing ribose, whereas control tendons (n = 6) were incubated in phosphate-buffered saline without ribose. Eight weeks following glycation, the biomechanical attributes as well as the degree of collagen cross-linking were determined to examine the potential associations between matrix stiffness and molecular properties of collagen. Compared to nonglycated tendons, the glycated tendons showed increased maximum load, stress, strain, Young''s modulus of elasticity, and toughness indicating that glycation increases the matrix stiffness in the tendons. Glycation of tendons resulted in a considerable decrease in soluble collagen content and a significant increase in insoluble collagen and pentosidine. Analysis of potential associations between the matrix stiffness and degree of collagen cross-linking showed that both insoluble collagen and pentosidine exhibited a significant positive correlation with the maximum load, stress, and strain, Young''s modulus of elasticity, and toughness (r values ranging from .61 to .94) in the Achilles tendons. However, the soluble collagen content present in neutral salt buffer, acetate buffer, and acetate buffer containing pepsin showed an inverse relation with the various biomechanical attributes tested (r values ranging from .22 to .84) in the Achilles tendons. The results of the study demonstrate that glycation-induced collagen cross-linking is directly associated with the increased matrix stiffness and other mechanical attributes of the tendon.     

Effect of exercise training on passive stiffness in locomotor skeletal muscle: role of extracellular matrix

The purpose ofthis study was to evaluate the effect of endurance exercise training onboth locomotor skeletal muscle collagen characteristics and passivestiffness properties in the young adult and old rat. Young(3-mo-old) and senescent (23-mo-old) male Fischer 344 rats wererandomly assigned to either a control or exercise training group[young control (YC), old control (OC), young trained (YT), oldtrained (OT)]. Exercise training consisted of treadmill runningat ~70% of maximal oxygen consumption (45 min/day, 5 days/wk, for 10 wk). Passive stiffness (stress/strain) of the soleus (Sol) muscle fromall four groups was subsequently measured in vitro at 26°C.Stiffness was significantly greater for Sol muscles in OC rats comparedwith YC rats, but in OT rats exercise training resulted in muscles withstiffness characteristics not different from those in YC rats. Solmuscle collagen concentration and the level of the nonreduciblecollagen cross-link hydroxylysylpyridinoline (HP) significantlyincreased from young adulthood to senescence. Although training had noeffect on Sol muscle collagen concentration in either age group, itresulted in a significant reduction in the level of Sol muscle HP in OTrats. In contrast, exercise had no effect on HP in the YT animals.These findings indicate that 10 wk of endurance exercise significantlyalter the passive viscoelastic properties of Sol muscle in old but notin young adult rats. The coincidental reduction in the principalcollagen cross-link HP also observed in response to training in OTmuscle highlights the potential role of collagen in influencing passivemuscle viscoelastic properties.

     

Exercise training and muscle microvascular oxygenation: functional role of nitric oxide

Exercise training induces multiple adaptations within skeletal muscle that may improve local O(2) delivery-utilization matching (i.e., Po(2)mv). We tested the hypothesis that increased nitric oxide (NO) function is intrinsic to improved muscle Po(2)mv kinetics from rest to contractions after exercise training. Healthy young Sprague-Dawley rats were assigned to sedentary (n = 18) or progressive treadmill exercise training (n = 10; 5 days/wk, 6-8 wk, final workload of 60 min/day at 35 m/min, -14% grade) groups. Po(2)mv was measured via phosphorescence quenching in the spinotrapezius muscle at rest and during 1-Hz twitch contractions under control (Krebs-Henseleit solution), sodium nitroprusside (SNP, NO donor; 300 μM), and N(G)-nitro-l-arginine methyl ester (l-NAME, nonspecific NO synthase blockade; 1.5 mM) superfusion conditions. Exercise-trained rats had greater peak oxygen uptake (Vo(2peak)) than their sedentary counterparts (81 ± 1 vs. 72 ± 2 ml·kg(-1)·min(-1), respectively; P < 0.05). Exercise-trained rats had significantly slower Po(2)mv fall throughout contractions (τ(1); time constant for the first component) during control (sedentary: 8.1 ± 0.6; trained: 15.2 ± 2.8 s). Compared with control, SNP slowed τ(1) to a greater extent in sedentary rats (sedentary: 38.7 ± 5.6; trained: 26.8 ± 4.1 s; P > 0.05) whereas l-NAME abolished the differences in τ(1) between sedentary and trained rats (sedentary: 12.0 ± 1.7; trained: 11.2 ± 1.4 s; P < 0.05). Our results indicate that endurance exercise training leads to greater muscle microvascular oxygenation across the metabolic transient following the onset of contractions (i.e., slower Po(2)mv kinetics) partly via increased NO-mediated function, which likely constitutes an important mechanism for training-induced metabolic adaptations.     

Matrix remodeling in experimental and human heart failure: a possible regulatory role for TIMP-3

In the failing heart, an imbalance in matrix metalloproteinases (MMPs) and their biological regulators, the tissue inhibitors of MMPs (TIMPs), may result in cardiac dilatation from matrix degradation. We hypothesized that a reduction of myocardial TIMP-3 is associated with adverse matrix remodeling in both human and experimental heart failure. Cardiomyopathic hamsters at age 15 wk (normal), 25 wk (compensated stage), and 35 wk (overt failure) were compared with age-matched normal controls. MMP activity (gelatinase bioassay) was increased in cardiomyopathic hearts (P = 0.03) and peaked during the transition to overt heart failure. TIMP-3 content (immunoblot) was decreased compared with normal controls (74 +/- 5% at 25 wk, 69 +/- 10% at 35 wk; P = 0.001) and its reduction was associated with increased MMP activity (r = -0.6; P = 0.004). TIMP-1 increased progressively (P = 0.001), whereas TIMP-2, TIMP-4, and MMP protein levels were unchanged. Myocardial collagen (hydroxyproline content) increased with time during the progression to end-stage cardiac failure (P < 0.0001). Collagen synthesis ([(14)C]proline uptake) was elevated in cardiomyopathy at 15 and 25 wk (P < 0.05). The collagen cross-linking ratio (insoluble:soluble collagen) was reduced (P = 0.003) as the left ventricle dilated. By confocal microscopy restricted to viable myocardium, collagen content was reduced (P = 0.04) with fragmentation (P < 0.0001) and thinning (P = 0.003) of perimysial collagen fibers. Similarly, patients with end-stage congestive heart failure (n = 7) compared with nonfailing controls (n = 2) had elevated gelatinase MMP activity (P = 0.02) associated with isolated reductions in TIMP-3 (55 +/- 5% of normal; P = 0.003). Reductions of TIMP-3 parallel adverse matrix remodeling in the cardiomyopathic hamster and the failing human heart. TIMP-3 may contribute to the regulation of myocardial remodeling and its reduction may promote a transition from compensated to end-stage congestive heart failure.     

Effect of rowing ergometry and oral volume loading on cardiovascular structure and function during bed rest

This study examined the effectiveness of a short-duration but high-intensity exercise countermeasure in combination with a novel oral volume load in preventing bed rest deconditioning and orthostatic intolerance. Bed rest reduces work capacity and orthostatic tolerance due in part to cardiac atrophy and decreased stroke volume. Twenty seven healthy subjects completed 5 wk of -6 degree head down bed rest. Eighteen were randomized to daily rowing ergometry and biweekly strength training while nine remained sedentary. Measurements included cardiac mass, invasive pressure-volume relations, maximal upright exercise capacity, and orthostatic tolerance. Before post-bed rest orthostatic tolerance and exercise testing, nine exercise subjects were given 2 days of fludrocortisone and increased salt. Sedentary bed rest led to cardiac atrophy (125 ± 23 vs. 115 ± 20 g; P < 0.001); however, exercise preserved cardiac mass (128 ± 38 vs. 137 ± 34 g; P = 0.002). Exercise training preserved left ventricular chamber compliance, whereas sedentary bed rest increased stiffness (180 ± 170%, P = 0.032). Orthostatic tolerance was preserved only when exercise was combined with volume loading (-10 ± 22%, P = 0.169) but not with exercise (-14 ± 43%, P = 0.047) or sedentary bed rest (-24 ± 26%, P = 0.035) alone. Rowing and supplemental strength training prevent cardiovascular deconditioning during prolonged bed rest. When combined with an oral volume load, orthostatic tolerance is also preserved. This combined countermeasure may be an ideal strategy for prolonged spaceflight, or patients with orthostatic intolerance.     

Immature tendon adaptation to strenuous exercise

White Leghorn roosters (3 wk old) were randomly assigned to runner or control groups. Runners were subjected to a progressive treadmill running program for 8 wk, 5 days/wk at 70-80% maximal O2 consumption (VO2 max). After 8 wk, runners showed a significant elevation in gastrocnemius fumarase activity (51%) and a 21% increase in VO2max compared with controls. The exercise program induced a significant increase in tendon collagen deposition (46%) without any changes in DNA, proteoglycan, and collagen concentrations or tendon dry weight. Also, tendon collagen from runners contained fewer (50%) pyridinoline cross-links. These results suggest that high-intensity exercise causes greater matrix-collagen turnover in growing chickens, resulting in reduced maturation of tendon collagen.     

Effects of long-term immobilization and recovery on human triceps surae and collagen turnover in the Achilles tendon in patients with healing ankle fracture.

The aim of the present study was to analyze how human tendon connective tissue responds to an approximately 7-wk period of immobilization and a remobilization period of a similar length, in patients with unilateral ankle fracture, which is currently unknown. Calf muscle cross-sectional area (CSA) decreased by 15% (5,316 to 4,517 mm2) and strength by 54% (239 to 110 N.m) in the immobilized leg after 7 wk. During the 7-wk remobilization, the CSA increased by 9% (to 4,943 mm2) and strength by 37% (to 176 Nm). Achilles tendon CSA did not change significantly during either immobilization or remobilization. Local collagen turnover was measured as the peritendinous concentrations of NH2-terminal propeptide of type I collagen (PINP) and COOH-terminal telopeptide region of type I collagen (ICTP), markers thought to be indexes of type I collagen synthesis and degradation, respectively. Both markers were increased (PINP: 257 vs. 56 ng/ml; ICTP: 9.8 vs. 2.1 microg/l) in the immobilized leg compared with the control leg after the 7 wk of immobilization, and levels decreased again in the immobilized leg during the recovery period (PINP: 103 vs. 44 ng/ml; ICTP: 4.2 vs. 1.9 microg/l). A significant reduction in calf muscle CSA and strength was found in relation to 7 wk of immobilization. Immobilization increased both collagen synthesis and degradation in tendon near tissue. However, it cannot be excluded that the facture of the ankle in close proximity could have affected these data. Remobilization increased muscle size and strength and tendon synthesis and degradation decreased to baseline levels. These dynamic changes in tendon connective tissue turnover were not associated with macroscopic changes in tendon size.     

Influence of acetaminophen and ibuprofen on skeletal muscle adaptations to resistance exercise in older adults

Evidence suggests that consumption of over-the-counter cyclooxygenase (COX) inhibitors may interfere with the positive effects that resistance exercise training has on reversing sarcopenia in older adults. This study examined the influence of acetaminophen or ibuprofen consumption on muscle mass and strength during 12 wk of knee extensor progressive resistance exercise training in older adults. Thirty-six individuals were randomly assigned to one of three groups and consumed the COX-inhibiting drugs in double-blind placebo-controlled fashion: placebo (67 ± 2 yr; n = 12), acetaminophen (64 ± 1 yr; n = 11; 4 g/day), and ibuprofen (64 ± 1 yr; n = 13; 1.2 g/day). Compliance with the resistance training program (100%) and drug consumption (via digital video observation, 94%), and resistance training intensity were similar (P > 0.05) for all three groups. Drug consumption unexpectedly increased muscle volume (acetaminophen: 109 ± 14 cm(3), 12.5%; ibuprofen: 84 ± 10 cm(3), 10.9%) and muscle strength (acetaminophen: 19 ± 2 kg; ibuprofen: 19 ± 2 kg) to a greater extent (P < 0.05) than placebo (muscle volume: 69 ± 12 cm(3), 8.6%; muscle strength: 15 ± 2 kg), when controlling for initial muscle size and strength. Follow-up analysis of muscle biopsies taken from the vastus lateralis before and after training showed muscle protein content, muscle water content, and myosin heavy chain distribution were not influenced (P > 0.05) by drug consumption. Similarly, muscle content of the two known enzymes potentially targeted by the drugs, COX-1 and -2, was not influenced (P > 0.05) by drug consumption, although resistance training did result in a drug-independent increase in COX-1 (32 ± 8%; P < 0.05). Drug consumption did not influence the size of the nonresistance-trained hamstring muscles (P > 0.05). Over-the-counter doses of acetaminophen or ibuprofen, when consumed in combination with resistance training, do not inhibit and appear to enhance muscle hypertrophy and strength gains in older adults. The present findings coupled with previous short-term exercise studies provide convincing evidence that the COX pathway(s) are involved in the regulation of muscle protein turnover and muscle mass in humans.     

Aging and exercise training reduce testes microvascular PO2 and alter vasoconstrictor responsiveness in testicular arterioles

Testicular function and associated testosterone concentration decline with advancing age, and an impaired O? supply may contribute, in part, to this reduction. We hypothesized that there would be a reduced microvascular Po? (Po?(m)) in the testes from aged rats, and this reduced Po?(m) would be associated with impaired vasomotor control in isolated resistance arterioles. In addition, given the positive effect of exercise on microvascular Po? and arteriolar function, we further hypothesized that there would be an enhanced Po?(m) in the testes from aged animals after aerobic exercise training. Testicular Po?(m) was measured in vivo via phosphorescence quenching in young and aged sedentary (SED) and exercise-trained (ET; 15 m/min treadmill walking, 15-degree incline, 5 days/wk for 10 wk) male Fischer-344 rats. Vasoconstriction to α-adrenergic [norepinephrine (NE) and phenylephrine (PE)] and myogenic stimuli in testicular arterioles was assessed in vitro. In the SED animals, testicular Po?(m) was reduced by ～50% with old age (aged SED 11.8 ± 1.9 vs. young SED 22.1 ± 1.1 mmHg; P = 0.0001). Contrary to our hypothesis, exercise training did not alter Po?(m) in the aged group and reduced testicular Po?(m) in the young animals, abolishing age-related differences (young ET, 10.0 ± 0.8 vs. aged ET, 10.7 ± 0.9 mmHg; P = 0.37). Vasoconstrictor responsiveness to NE and PE was diminished in aged compared with young (NE: young SED, 58 ± 2 vs. aged SED, 47 ± 2%; P = 0.001) (PE: young SED, 51 ± 3 vs. aged SED, 36 ± 5%; P = 0.008). Exercise training did not alter maximal vasoconstriction to NE in young or aged groups. In summary, advancing age is associated with a reduced testis Po?(m) and impaired adrenergic vasoconstriction. The diminished testicular microvascular driving pressure of O? and associated vascular dysfunction provides mechanistic insight into the old age-related decrease in testicular function, and a reduced Po?(m) may contribute, in part, to reduced fertility markers after exercise training.     

Exercise training augments the dynamic heart rate response to vagal but not sympathetic stimulation in rats

We examined the transfer function of autonomic heart rate (HR) control in anesthetized sedentary and exercise-trained (16 wk, treadmill for 1 h, 5 times/wk at 15 m/min and 15-degree grade) rats for comparison to HR variability assessed in the conscious resting state. The transfer function from sympathetic stimulation to HR response was similar between groups (gain, 4.2 ± 1.5 vs. 4.5 ± 1.5 beats·min(-1)·Hz(-1); natural frequency, 0.07 ± 0.01 vs. 0.08 ± 0.01 Hz; damping coefficient, 1.96 ± 0.55 vs. 1.69 ± 0.15; and lag time, 0.7 ± 0.1 vs. 0.6 ± 0.1 s; sedentary vs. exercise trained, respectively, means ± SD). The transfer gain from vagal stimulation to HR response was 6.1 ± 3.0 in the sedentary and 9.7 ± 5.1 beats·min(-1)·Hz(-1) in the exercise-trained group (P = 0.06). The corner frequency (0.11 ± 0.05 vs. 0.17 ± 0.09 Hz) and lag time (0.1 ± 0.1 vs. 0.2 ± 0.1 s) did not differ between groups. When the sympathetic transfer gain was averaged for very-low-frequency and low-frequency bands, no significant group effect was observed. In contrast, when the vagal transfer gain was averaged for very-low-frequency, low-frequency, and high-frequency bands, exercise training produced a significant group effect (P < 0.05 by two-way, repeated-measures ANOVA). These findings suggest that, in the frequency domain, exercise training augments the dynamic HR response to vagal stimulation but not sympathetic stimulation, regardless of the frequency bands.     

Uphill running improves rat Achilles tendon tissue mechanical properties and alters gene expression without inducing pathological changes

Overuse Achilles tendinopathy is a common and challenging problem in sports medicine. Little is known about the etiology of this disorder, and the development of a good animal model for overuse tendinopathy is essential for advancing insight into the disease mechanisms. Our aim was to test a previously proposed rat model for Achilles tendon overuse. Ten adult male Sprague-Dawley rats ran on a treadmill with 10° incline, 1 h/day, 5 days/wk (17-20 m/min) for 12 wk and were compared with 12 control rats. Histological, mechanical, and gene-expression changes were measured on the Achilles tendons after the intervention, and local tendon glucose-uptake was measured before and after the intervention with positron emission tomography. No differences were detected between runners and controls in tissue histology or in glucose uptake, indicating that tendon pathology was not induced. Greater tendon tissue modulus (P < 0.005) and failure stress/body weight (P < 0.02) in runners compared with controls further supported that tendons successfully adapted to uphill running. Several genes of interest were regulated after 12 wk of running. Expression of collagen III and insulin-like growth factor I was increased, while collagen I was unchanged, and decreases were seen in noncollagen matrix components (fibromodulin and biglycan), matrix degrading enzymes, transforming growth factor-β1, and connective tissue growth factor. In conclusion, the tested model could not be validated as a model for Achilles tendinopathy, as the rats were able to adapt to 12 wk of uphill running without any signs of tendinopathy. Improved mechanical properties were observed, as well as changes in gene-expression that were distinctly different from what is seen in tendinopathy and in response to short-term tendon loading.     

Exercise-dependent IGF-I, IGFBPs, and type I collagen changes in human peritendinous connective tissue determined by microdialysis.

Microdialysis studies indicate that mechanical loading of human tendon during exercise elevates type I collagen production in tendon. However, the possibility that the insertion of microdialysis fibers per se may increase the local collagen production due to trauma has not been explored. Insulin-like growth factor I (IGF-I) and its binding proteins (IGFBPs), which are known to stimulate collagen production in animal tendons, may regulate the translation of mechanical loading to collagen synthesis. Systemic and tissue levels of IGF-I, IGFBP, and type I collagen metabolism markers [procollagen I COOH-terminal propeptide (PICP) and COOH-terminal telopeptide of type I collagen] were measured by microdialysis in peritendinous tissue of the human Achilles tendon in an exercise group (performing a 36-km run, n = 6) and a control group (no intervention, n = 6). An increase in local PICP concentration was seen in both groups after 72 h and stayed elevated in the exercise group at 96 h (P < 0.05). IGFBP-1 in both serum and dialysate increased in the exercise group immediately after exercise (P < 0.05), whereas IGFBP-3 decreased systemically (P < 0.05). Elevation of local IGFBP-4 was observed in both the control and exercise groups after 48 h (P < 0.05). Total IGF-I did not change in locally or systemically in either group. Our results indicate an increased local production of PICP in human peritendinous tissue in response to prolonged mechanical loading with part of the increase due to trauma from the sampling technique. Care must therefore be emphasized to minimize the numbers of insertions with microdialysis. We demonstrated an elevation of IGFBP-1 both systemically and peritendinously in response to prolonged acute exercise. The local increased collagen synthesis was preceded by an elevation of local concentration of IGFBP-4, suggesting that IGFBP-4 may have a key role in the IGF-axis effect on the human collagen synthesis in vivo.     

Tendon collagen synthesis at rest and after exercise in women.

In general, there is a higher incidence of musculoskeletal injuries during physical activity in women than in men. We hypothesized that in women rates of tendon collagen synthesis would be lower than in men at rest and after exercise, especially in the later luteal phase when estrogen and progesterone concentrations are higher than the early follicular phase. We studied tendon collagen fractional synthesis rate (FSR) in 15 young, healthy female subjects in either the early follicular (n = 8) or the late luteal phase (n = 7) 72 h after an acute bout of one-legged exercise (60 min kicking at 67% workload maximum) (72 h) and compared the results with those previously obtained for men. Samples were taken from the patellar tendon in both the exercised and rested legs to determine collagen FSR by the incorporation of [15N]proline into tendon collagen hydroxyproline. There was no effect of menstrual phase on tendon collagen synthesis either at rest or after exercise. However, there was a significant difference between women and men at rest (women = 0.025 +/- 0.002%/h, men = 0.045 +/- 0.008%/h; P < 0.05) and 72 h after exercise (women = 0.027 +/- 0.005%/h; men = 0.058 +/- 0.008%/h). Furthermore, rest and 72-h tendon collagen synthesis were not different in women, whereas in men tendon collagen synthesis remained significantly elevated 72 h after exercise. It is concluded that both in the resting state and after exercise, tendon collagen FSR is lower in women than in men, which may contribute to a lower rate of tissue repair after exercise.     

Exercise-induced regulation of muscular Na+-K+ pump, FXYD1, and NHE1 mRNA and protein expression: importance of training status, intensity, and muscle type

It is investigated if exercise-induced mRNA changes cause similar protein expression changes of Na(+)-K(+) pump isoforms (α(1), α(2), β(1), β(2)), FXYD1, and Na(+)/K(+) exchanger (NHE1) in rat skeletal muscle. Expression was evaluated (n = 8 per group) in soleus and extensor digutorum longus after 1 day, 3 days, and 3 wk (5 sessions/wk) of either sprint (4 × 3-min sprint + 1-min rest) or endurance (20 min) running. Two hours after exercise on day 1, no change in protein expression was apparent in either training group or muscle, whereas sprint exercise increased the mRNA of soleus α(2) (4.9 ± 0.8-fold; P < 0.05), β(2) (13.2 ± 4.4-fold; P < 0.001), and NHE1 (12.0 ± 3.1-fold; P < 0.01). Two hours after sprint exercise, protein expression normalized to control samples was higher on day 3 than day 1 for soleus α(1) (41 ± 18% increase vs. 15 ± 8% reduction; P < 0.05), α(2) (64 ± 35% increase vs. 37 ± 12% reduction; P < 0.05), β(1) (17 ± 21% increase vs. 14 ± 29% reduction; P < 0.05), and FXYD1 (35 ± 16% increase vs. 13 ± 10% reduction; P < 0.05). In contrast, on day 3, soleus α(1) (0.1 ± 0.1-fold; P < 0.001), α(2) (0.2 ± 0.1-fold; P < 0.001), β(1) (0.4 ± 0.1-fold; P < 0.05), and β(2)-mRNA (2.9 ± 1.7-fold; P < 0.001) expression was lower than after exercise on day 1. After 3 wk of training, no change in protein expression relative to control existed. In conclusion, increased expression of Na(+)-K(+) pump subunits, FXYD1 and NHE1 after 3 days exercise training does not appear to be an effect of increased constitutive mRNA levels. Importantly, sprint exercise can reduce mRNA expression concomitant with increased protein expression.     

短跑训练对运动员跟腱影响的超声测量研究

目的：研究短跑训练对运动员跟腱的影响。方法：选择从事运动训练4-6年的健康男、女短跑运动员为实验组（n=12）,同时选同龄健康非运动员男、女为对照组（n=12）,采用高频超声检测平静状态跟腱长度、横截面积,以及小腿三头肌等长收缩最大力量跖屈跟腱长度的变化。结果：跟腱长度：对照组男子168.5±9.2mm,女子162.4±9.8mm,实验组男子170.9±10.7mm,女子164.0±7.0mm。实验组和对照组组内、组间差别均无统计学意义。跟腱横截面积：对照组男子62.2±6.2mm2,女子47.1±4.5mm2,实验组男子65.6±2.9mm2,女子49.6±1.9mm2。同组内男子比女子跟腱横截面积大,差别有统计学意义（P＆lt;0.05）,但实验组和对照组组间差别无统计学意义。小腿三头肌等长收缩最大力跖屈时跟腱拉长值：对照组男子7.6±3.6mm,女子4.9±2.8mm,实验组男子11.1±2.9mm,女子7.9±3.1mm。男子比女子跟腱拉长值大、实验组比对照组拉长值大,差别均有统计学意义（P＆lt;0.05）。结论：短跑训练可增加跟腱可拉伸长度,跟腱的长度和横截面积未发生明显变化。高频超声可作为重要的测量手段用于...