Exercise training eliminates age-related differences in skeletal muscle insulin receptor and IRS-1 abundance in rats.

Insulin resistance is common in old age, and exercise training can improve insulin sensitivity. The purpose of this study was to determine the influence of age (6 vs 26 months) and exercise training (10 weeks of treadmill running) on insulin signaling protein abundance in skeletal muscle from male Fisher 344 rats. Muscle levels of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), and Akt1, a serine-threonine kinase, were determined. IRS-1 was reduced with aging, IR and PI3K abundance was greater in old rats, and Akt1 was unchanged. IRS-1 was increased by training in old but not young rats, and IR was increased by training in young but not old rats. PI3K tended to increase and Akt1 did not change with training, regardless of age. Aging does not uniformly affect insulin signaling protein abundance, and exercise differentially alters IR and IRS-1 in young and old rats, thereby eliminating age-related differences in these proteins.

Exercise training attenuates aging-associated increases in collagen and collagen crosslinking of the left but not the right ventricle in the rat.

The purpose of this study was to compare the independent and interactive effects of age and exercise training on selected parameters of the right ventricle (RV), left ventricular septum (LVS) and left ventricular free-wall (LVFW) extracellular matrix. Specifically, we evaluated collagen and collagen crosslinking (hydroxylysylpyridinoline, HP) concentrations in the myocardial extracellular matrix in young adult, Y (5.5 months) and old, O (25.5 months) male Fischer 344 rats. Rats were assigned to either a sedentary control (YC, OC) or an exercise training group (YT, OT). Rats were trained for 45 min/day, 5 days/week, for 10 weeks at approximately equals 70% of maximal oxygen consumption. Following the training regimen, rats were sacrificed and their hearts were dissected into the RV, LVS and LVFW. Training resulted in a significant hypertrophy of the left ventricle (LV) but not RV relative to body weight. In young rats, collagen concentration was significantly higher (P<0.01) in RV compared to LVS, but not LVFW. With aging, collagen concentration increased significantly (P<0.05) in both ventricles, but more so in LV than RV so that differences in percent collagen observed between chambers in both YC and YT rats no longer existed in OC and OT animals. This aging effect was attenuated by training in the LVS but not the LVFW, so that collagen concentration, while higher in this region of the LV in OT compared to YT rats, was also lower than that seen in the LVS of OC rats. HP crosslink concentration in the LVS and LVFW, but not the RV of OC rats was significantly elevated above corresponding values seen in YC rats (P < 0.05 or greater). In YT rats, training had no effect on HP crosslinking concentration in any of the three regions of the heart. However, in OT rats, training completely prevented the age-associated increase in crosslinking seen in both the LVS and LVFW of OC animals. These findings illustrate the different responses of the RV, LVS and LVFW extracellular matrix components, collagen and HP crosslinking, to both aging and training in the rodent.

Impact of prednisone on TGF-beta1 and collagen in diaphragm muscle from mdx mice.

The purpose of this study was to assess the impact of prednisone treatment for 8 weeks on the level of transforming growth factor-beta 1 (TGF-beta1), hydroxyproline (HYP) concentrations, and level of the mature, nonreducible collagen cross-link hydroxylysylpyridinoline (HP) in diaphragm muscle from 12-week-old mdx mice. Diaphragm muscle from untreated mdx mice had a significantly higher level of TGF-beta1, HYP, and HP cross-link compared with normal C57BL/10J (control) mice. Prednisone treatment significantly reduced the level of TGF-beta1 and HYP in diaphragm from mdx mice to values similar to control mice, but resulted in a higher level of the HP cross-link compared with untreated mdx mice. These findings indicate that short-term treatment of mdx mice with prednisone can attenuate the fibrotic response in diaphragm muscle, possibly by mediating the level of TGF-beta. Although prednisone was beneficial in preventing collagen accumulation, it resulted in a higher level of the HP cross-link, presumably by decreasing collagen turnover

Impact of mechanical load on functional recovery after muscle reloading.

The purposes of this study included: 1) to determine the impact of reloading after hindlimb suspension on the in vitro isometric contractile properties of the rat soleus muscle (experiment 1), and 2) to determine the impact of altered mechanical load on the recovery of muscle contractile properties after reloading-induced injury (experiment 2). Male Sprague-Dawley rats (240-270 g) were used for both experiments. In experiment 1, all rats were hindlimb suspended for a period of 7 d and studied either immediately afterward (no reloading, 0D-RL), after 1 d (24 h) of reloading (1D-RL), or after 2 d (48 h) reloading (2D-RL). In experiment 2, all rats underwent hindlimb suspension for 7 d followed by reloading for 2 d. Rats were then randomly assigned to one of three groups: 1) cage-bound, 2) treadmill walking (12m x min(-1) x 20 min daily), or 3) resuspended. Rats were then studied 7 or 14 d later. In experiment 1, maximal isometric specific force (force/cross-sectional area, Po) was significantly decreased by approximately 32% and approximately 50% in the ID-RL and 2D-RL groups (P < 0.05) compared with 0D-RL group. During the recovery phase (experiment 2), Po was significantly higher in the cage-bound and treadmill walking groups compared with the resuspended group both at 7 and 14 d. However, there was no significant difference in Po between the cage-bound and treadmill walking groups at either time point. Results from this study indicate that skeletal muscle reloading (after a period of unloading) results in a significant force decrement. Additionally, removal of the load during the recovery phase significantly impairs functional recovery, whereas mild exercise offers no advantage over cage-bound activity.

Endogenous opioids modulate ventilation and peak oxygen consumption in obese Zucker rats.

Levels of endogenous opioids are increased in morbidly obese humans and obese rats. Endogenous opioids are important neuromodulators, and are involved in a wide range of functions including ventilatory control. We studied eight lean and eight obese Zucker (Z) rats at 6 and 16 wk of age. We assessed minute ventilation (V E) at rest and during hypercapnic challenges, as well as peak oxygen consumption (V O(2peak)) after the administration of saline (control), naloxone hydrochloride (N(HCl)), and naloxone methiodide (N(M)). Administration of N(HCl) and N(M) to lean animals had no effect on V E and V O(2peak). Similarly, N(M) failed to alter V E and V O(2peak) in obese rats studied at 6 or 16 wk of age. In young obese rats, N(HCl) significantly (p < 0.05) increased resting V E (721 +/- 154 [mean +/- SD] ml/kg/min versus 937 +/- 207 ml/kg/min, saline versus N(HCl), respectively); VE in response to 4% CO(2) (924 +/- 110 ml/kg/min versus 1,212 +/- 172 ml/ kg/min); V E in response to 8% CO(2) (1,233 +/- 172 ml/kg/min versus 1,565 +/- 327 ml/kg/min); and V O(2peak) (90.8 +/- 9.6 ml/kg(0.75)/min versus 98.3 +/- 5.9 ml/kg(0.75)/min). However, N(HCl) administration had no effect on V E or V O(2peak) in obese rats retested at 16 wk of age. Thus, endogenous opioids modulate resting ventilation, ventilatory responsiveness to CO(2), and V O(2peak) in young obese rats by acting specifically on receptors located within the central nervous system. This modulation disappears once the animals reach 16 wk of age.

Attenuation of force deficit after lengthening contractions in soleus muscle from trained rats.

The purposes of this study were 1) to determine the extent to which endurance training reduces the functional deficit induced by lengthening contractions in the soleus (Sol) muscle and 2) to determine whether young and old rats training at a comparable relative exercise intensity would demonstrate a similar protective effect from lengthening-contraction-induced injury. Young (3-mo-old) and old (23-mo-old) male Fischer 344 rats were randomly assigned to either a control or exercise training group [young control (YC), old control (OC), young trained (YT), old trained (OT)]. Exercise training consisted of 10 wk of treadmill running (15% grade, 45 min/day, and 5 days/wk) such that by the end of training the young and old rats were exercising at 27 and 15 m/min, respectively. After training, contractile properties of the Sol muscle were measured in vitro at 26 degrees C. The percent decrease in maximal isometric specific force (P(o)) was determined after a series of 20 lengthening contractions (20% strain from optimal muscle length, 1 contraction every 5 s). After the lengthening-contraction protocol, Sol muscle P(o) was decreased by approximately 26% (19.6 vs. 14.6 N/cm(2)) and 28% (14.8 vs. 9.6 N/cm(2)) in the YC and OC rats, respectively. After exercise training, the reduction in P(o) was significantly (P < 0.05) attenuated to a similar degree ( approximately 13%) in both YT rats (18.7 vs. 16.2 N/cm(2)) and OT rats (15.8 vs. 13.7 N/cm(2)). It is concluded that exercise training attenuates the force deficit after repeated lengthening contractions to a comparable extent in young and old rats training at a similar exercise intensity.

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

The purpose of this study was to evaluate the effect of endurance exercise training on both locomotor skeletal muscle collagen characteristics and passive stiffness properties in the young adult and old rat. Young (3-mo-old) and senescent (23-mo-old) male Fischer 344 rats were randomly assigned to either a control or exercise training group [young control (YC), old control (OC), young trained (YT), old trained (OT)]. Exercise training consisted of treadmill running at approximately 70% of maximal oxygen consumption (45 min/day, 5 days/wk, for 10 wk). Passive stiffness (stress/strain) of the soleus (Sol) muscle from all four groups was subsequently measured in vitro at 26 degreesC. Stiffness was significantly greater for Sol muscles in OC rats compared with YC rats, but in OT rats exercise training resulted in muscles with stiffness characteristics not different from those in YC rats. Sol muscle collagen concentration and the level of the nonreducible collagen cross-link hydroxylysylpyridinoline (HP) significantly increased from young adulthood to senescence. Although training had no effect on Sol muscle collagen concentration in either age group, it resulted in a significant reduction in the level of Sol muscle HP in OT rats. In contrast, exercise had no effect on HP in the YT animals. These findings indicate that 10 wk of endurance exercise significantly alter the passive viscoelastic properties of Sol muscle in old but not in young adult rats. The coincidental reduction in the principal collagen cross-link HP also observed in response to training in OT muscle highlights the potential role of collagen in influencing passive muscle viscoelastic properties.

Respiratory muscle reserve in rats during heavy exercise.

The extent to which the respiratory pump muscles limit maximal aerobic capacity in quadrupeds is not entirely clear. To examine the effect of reduced respiratory muscle reserve on aerobic capacity, whole body peak oxygen consumption (VO2 peak) was measured in healthy Sprague-Dawley rats before and after Sham, unilateral, or bilateral hemidiaphragm denervation (Dnv) surgery. VO2 peak was determined by using a graded treadmill running test. Hemidiaphragm paralysis was verified after testing by recording the absence of electromyographic activity during inspiration. Before surgery, VO2 peak averaged 86, 87, and 92 ml . kg-1 . min-1 for the Sham, unilateral, and bilateral Dnv groups, respectively. Two weeks after surgery, there was no significant change in VO2 peak for either the Sham or unilateral Dnv group. However, VO2 peak decreased approximately 19% in the bilateral Dnv group 2 wk after surgery. These findings strongly suggest that the pulmonary system in rats is designed such that during heavy exercise, the remaining respiratory pump muscles are able to compensate for the loss of one hemidiaphragm, but not of both.

Alterations of diaphragm neuromuscular junctions with hypothyroidism.

Hypothyroidism (HYPO) often manifests as neuromuscular symptoms; however, little is known about its effects on the neuromuscular junction (NMJ). The present study examined changes in NMJ morphology and neuromuscular transmission failure (NTF) in the rat diaphragm muscle (Dimus) after 3 wk of HYPO. Three-color fluorescence immunocytochemistry and confocal microscopy were used to simultaneously visualize nerve terminals and axons, motor end plates, and myosin heavy chain isoform expression in Dimus fibers. NTF was assessed in vitro by comparing muscle fatigue induced by nerve with that induced by direct muscle stimulation. Diameters of axons innervating type I fibers were 30% smaller in the HYPO Dimus than in control (CTL). Planar areas of nerve terminals and end plates on type I and IIa fibers were 15-35% smaller in HYPO than in CTL. The extent of overlap between nerve terminals and end plates of type I fibers was 10% less in HYPO. Susceptibility to NTF during repetitive nerve stimulation was 20% greater in the CTL Dimus than in HYPO; however, changes in NMJ morphology could not fully account or the effect of HYPO on NTF.

Hypothyroid-mediated changes in adult rat diaphragm muscle contractile properties and MHC isoform expression.

The purpose of the present study was to examine the effect of acute hypothyroidism on myosin heavy chain (MHC) isoform composition and contractile properties in the adult rat diaphragm muscle. Hypothyroidism was induced by the addition of propylthiouracil (0.05%) in the drinking water for a period of 3 wk. MHC isoform composition of control and hypothyroid diaphragm muscles was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In vitro isometric contractile properties of midcostal diaphragm muscle segements were measured at 26 degrees C, whereas the maximal unloaded shortening velocity was measured at 15 degrees C with the "slack test" method. Serum triiodothyronine and thyroxine values were significantly lower in the hypothyroid compared with the control group. A small but significant increase in the percentage of slow MHC isoform in the diaphragm was observed with acute hypothyroidism, whereas the percentage of the fast MHC isoforms (2A, 2X, and 2B) did not significantly differ between groups. Peak twitch force did not differ between groups. However, twitch contraction and half-relaxation times were significantly prolonged in the hypothyroid group compared with control. Maximal specific force was reduced in the hypothyroid compared with the control group, averaging 15.7 and 19.8 N/cm2, respectively (P < 0.05). The maximal unloaded shortening velocity averaged 4.3 and 8.2 muscle lengths/s in the hypothyroid and control groups, respectively (P < 0.05). We conclude that acute hypothyroidism results in alterations in adult diaphragm muscle contractile properties that cannot be attributed solely to changes in MHC isoform composition.

Changes in diaphragm muscle collagen gene expression after acute unilateral denervation.

The purpose of the present study was to examine the effects of acute (3 days) unilateral diaphragm denervation (DNV) on 1) levels of alpha 1(I) and alpha 1(III) procollagen mRNA; 2) collagen concentration [hydroxyproline (HYP)]; 3) amount of the nonreducible collagen cross-link hydroxylysylpyridinoline (HP); and 4) the passive force-length relationship of the muscle. The levels of alpha 1(I) and alpha 1(III) procollagen mRNA, HYP concentration, and amount of HP were measured in muscle segments from the midcostal region of DNV and intact (INT) hemidiaphragms of adult male Fischer 344 rats (250-300 g). The in vitro passive force-length relationship of DNV and INT hemidiaphragm was determined by lengthening and shortening the diaphragm muscle segments from 85 to 115% of optimal length at a constant velocity (0.6 optimal length/s). Three days after DNV, the level of alpha 1(I) procollagen mRNA was increased over 15-fold in the DNV hemidiaphragm compared with INT (P < 0.05), whereas the level of alpha 1(III) procollagen mRNA was increased by approximately sixfold in the DNV hemidiaphragm compared with INT (P < 0.05). Collagen (HYP) concentration did not differ between groups, averaging 8.7 and 8.9 micrograms/mg dry wt for the DNV and INT hemidiaphragms, respectively. In addition, there was no difference in the amount of the mature nonreducible collagen cross-link HP between the DNV and INT hemidiaphragms (0.66 vs. 0.76 mole HP/mole collagen, respectively). The amount of passive force developed during lengthening did not differ between DNV and INT hemidiaphragms. These data indicate that acute DNV of the hemidiaphragm is associated with an increase in the mRNA level of the two principal fibrillar collagen phenotypes in skeletal muscle. However, despite extensive muscle remodeling, the passive force-length relationship of the DNV hemidiaphragm is unaffected compared with the INT muscle.

Regional adaptations of rabbit diaphragm muscle fibers to unilateral denervation.

We hypothesized that adaptations of the rabbit diaphragm (Dia) after unilateral denervation (DNV) result from removal of a neural influence rather than from passive stress. Length changes of midcostal and sternal Dia regions were measured before and after DNV by using sonomicrometry. Midcostal fibers passively lengthened after DNV, whereas sternal fibers shortened. In both regions, these length changes were associated with minimal stress, as estimated from passive force-length relationships. Morphological and contractile adaptions of midcostal and sternal Dia regions were examined after 1 and 4 wk of DNV. In both Dia regions, type I fibers progressively hypertrophied, whereas type IIb fibers atrophied. After DNV, changes in isometric contraction were similar in both Dia regions. Twitch contraction and half-relaxation times increased, force-frequency relationships shifted leftward, and maximum tetanic force decreased. We conclude that passive length changes and mechanical stress are not the main determinants of the morphological and contractile adaptations of the Dia after unilateral DNV but that these adaptations result from DNV itself.

Age-related differences in diaphragm muscle injury after lengthening activations.

The susceptibility of postnatal day 15 and adult rat diaphragms (DIAs) to acute injury after repetitive isovelocity lengthening activations was examined in vitro. Forces were measured during two phases of each stimulation protocol: 1) isometric phase: during the first 300 ms of each 500-ms train, DIA length was not changed; and 2) isovelocity lengthening phase: during the remaining 200 ms of each stimulus train, DIA was lengthened at a constant velocity from 90 to 110% of optimal length. At maximal activation (75 Hz and a lengthening velocity of 1.0 optimal length per second), the maximum force measured during the isometric phase and that measured during the isovelocity lengthening phase were both greater in adult DIAs than in day 15 DIAs but both declined to a greater extent in adults with repetitive activation. Ultrastructural analysis showed that after lengthening activations muscle fiber injury was very evident in adult but much less prevalent in day 15 DIAs. This difference in susceptibility between the adult and day 15 DIAs did not depend on differences in peak force or absolute velocity of lengthening. We conclude that lengthening activations result in DIA injury and that the adult is more susceptible than its younger counterpart.

Histochemical and mechanical properties of diaphragm muscle in morbidly obese Zucker rats.

The purpose of the present study was to evaluate the effects of chronic mass loading produced by obesity on the structural and functional characteristics of the diaphragm in lean and obese Zucker rats. The trapezius muscle served as an internal control. The studies were carried out on 17 lean (303 +/- 24 g) and 16 obese (698 +/- 79 g) Zucker rats. We observed that the diaphragms from obese animals were restructured such that the overall contribution of type I and IIa fibers was significantly increased. As a consequence of this remodeling, overall diaphragm thickness was selectively greater in obese animals. In small isolated diaphragm bundles studied in vitro, we also detected a reduction in specific force in obese animals that was not detected in the trapezius muscle. In vitro fatigue resistance, assessed by repeated stimulation, was similar in muscles of lean and obese animals. Diaphragm fiber oxidative capacity (succinate dehydrogenase activity) was also comparable in lean and obese animals. We conclude that in obesity the diaphragm undergoes modest remodeling that may be beneficial in enhancing force generation.

Changes in satellite cell mitotic activity during acute period of unilateral diaphragm denervation.

The acute period of unilateral diaphragm denervation (DNV) is associated with increases in cell mitotic activity, protein synthesis, and muscle fiber hypertrophy. Our purpose was to determine whether acute unilateral diaphragm DNV is associated with changes in muscle isometric contractile properties, cross-sectional area of different muscle fiber types, mitotic activity of muscle fiber satellite cells, and muscle fiber ultrastructural properties indicative of injury. Adult male Fischer 344 rats underwent a right phrenicotomy, and DNV and intact (INT) hemidiaphragms were studied 72 h later. DNV hemidiaphragm displayed a significant decline in maximal isometric force (8.7 vs. 24.3 N/cm2) and a prolonged time to peak twitch force (47.8 vs. 37.5 ms) and time to half relaxation (72.3 vs. 44.3 ms) compared with INT contralateral hemidiaphragm (P < 0.05). DNV resulted in a significant increase in cross-sectional area of types I (33%), IIa (35%), and IIb (28%) fibers relative to INT hemidiaphragm (P < 0.05). Satellite cell mitotic activity (assessed by incorporation of bromodeoxyuridine) was approximately 5.5 times greater in DNV than in INT muscle (DNV 25.0 +/- 3.8, INT 4.5 +/- 1.4 labeled satellite cell nuclei/1,000 nuclei; P < 0.05). Ultrastructural examination of electron micrographs revealed alterations in Z-line and sarcomeric structure indicative of muscle injury. Cellular infiltration and segmental necrosis were also noted in some fibers. We conclude that acute unilateral diaphragm DNV results in muscle fiber injury that induces satellite cell activation. We also speculate that the specific force decrement associated with DNV is at least partially the result of muscle injury.

Age-related changes in diaphragm muscle contractile properties and myosin heavy chain isoforms.

The present study sought to examine the effects of aging on the isometric contractile and fatigue properties as well as the myosin heavy chain (MCH) isoform composition of the rat diaphragm muscle. Male Fischer 344 (F344) specific pathogen-free rats 6 and 24 mo old were used in the study. Peak twitch force was approximately 23% lower (p < 0.05) in the senescent diaphragm compared with the young. Time to peak twitch force and one-half relaxation time of twitch force did not differ between groups. There was a significant decrease (15 to 18%, p < 0.05) in the specific force (N/cm2) of the senescent diaphragm at all stimulation frequencies (10 to 100 Hz) examined. In addition, the fatigability of the diaphragm did not significantly differ between the two groups. No significant changes in the distribution of MHC 1 and 2A isoforms were observed with aging. However, the contribution of MHC 2X significantly decreased with senescence (young, 37.5%; senescent, 30.5%), whereas the contribution of MHC 2B in the senescent diaphragm was significantly higher (young, 6.5%; senescent, 15.0%; p < 0.05). We conclude that the age-related decline in diaphragm muscle specific force is caused by intrinsic factors other than changes in MHC composition.

Passive length-force properties of senescent diaphragm: relationship with collagen characteristics.

The purpose of this study was to examine the effect of aging on collagen concentration and extent of nonreducible collagen cross-linking as well as with the passive length-force relationship of the diaphragm muscle. Midcostal diaphragm muscle strips from young (6 mo) and senescent (24 mo) Fischer 344 rats were perfused in a tissue bath containing mammalian Ringers solution (25 degrees C) aerated with 95% O2-5% CO2. The segments were lengthened and shortened from 85 to 115% of optimal length (L(o)) at a constant velocity (0.6 L(o)/s), and the passive force was measured. Hydroxyproline (HYP) and the mature nonreducible collagen cross-link, hydroxylysylpyridinoline (HP), were measured by high-pressure liquid chromatography. The resting force at Lo did not differ between young and senescent diaphragm muscles. However, the senescent diaphragm exhibited greater passive force compared with the young (P < 0.05) at lengths > 110% of L(o). High-pressure liquid chromatography analysis revealed a higher concentration of HYP in the senescent compared with the young diaphragm (9.32 +/- 0.83 and 6.59 +/- 0.78 g HYP/mg dry wt, respectively; P < 0.05). Additionally, the content of HP was greater in the senescent compared with the young diaphragm (1.16 +/- 0.05 and 0.91 +/- 0.05 mol HP/mol collagen, respectively; P < 0.05). These results suggest that diaphragm collagen metabolism, maturation, and the passive length-force characteristics of the muscle are altered with senescence.

Interstitial space and collagen alterations of the developing rat diaphragm.

The effect of growth on the relative interstitial space [%total cross-sectional area (CSA)] and collagen content of the rat diaphragm muscle was examined at postnatal ages of 0, 7, 14, and 21 days as well as in adult males. The proportion of interstitial space relative to total muscle CSA was determined by computerized image analysis of lectin-stained cross sections of diaphragm muscle. To assess collagen content and extent of collagen maturation (i.e., cross-linking), high-pressure liquid chromatography analysis was used to measure hydroxyproline concentration and the nonreducible collagen cross-link hydroxylysylpyridinoline (HP), respectively. At birth, interstitial space accounted for approximately 47% of total diaphragm muscle CSA. During postnatal growth, the relative contribution of interstitial space decreased such that by adulthood the interstitial space accounted for approximately 18% of total muscle CSA. The change in relative interstitial space occurred without a concomitant change in hydroxyproline concentration. However, the concentration of HP markedly increased with age such that the adult diaphragm contained approximately 17 times more HP than at birth. These results indicate that during development the relative CSA occupied by interstitial space decreases as muscle fiber size increases. However, the reduction in relative interstitial space is not associated with a change in collagen concentration. Thus collagen density in the interstitial space may increase with age. It is possible that the observed changes in relative interstitial space and collagen influence the passive length-force properties of the diaphragm.

Endurance exercise training causes adrenal medullary hypertrophy in young and old Fischer 344 rats.

The purpose of the present investigation was to determine the effects of endurance exercise training on adrenal medullary volume and epinephrine content in young (5 month) and old (23 month) female Fischer 344 rats. Animals from each group underwent 10 weeks of treadmill running (60 minutes per day, 5 days per week). 72 hours following the last training session animals were killed and the adrenal glands removed for subsequent analysis. Plantaris muscle citrate synthase activity increased with training in both young and old animals (39.8% young; 36.4% old). Trained animals had larger adrenal medullary volumes (48% increase in young, and 18% in old) than untrained controls. Trained animals also had higher total adrenal medullary epinephrine content (36% increase in young, and 24% in old). There were no differences in adrenal medullary epinephrine or norepinephrine concentration (micrograms/microliters medulla). It was concluded that the training-induced increase in adrenal epinephrine content is due to an increase in the size of the medulla, and not to a greater medullary epinephrine concentration. Furthermore, similar responses to training occur in both old and young animals.

Myosin heavy chain composition in the rat diaphragm: effect of age and exercise training.

Increases in aerobic capacity in both young and senescent rats consequent to endurance exercise training are now known to occur not only in locomotor skeletal muscle but also in diaphragm. In the current study the effects of aging and exercise training on the myosin heavy chain (MHC) composition were determined in both the costal and crural diaphragm regions of female Fischer 344 rats. Exercise training [treadmill running at 75% maximal oxygen consumption (1 h/day, 5 day/wk, x 10 wk)] resulted in similar increases in plantaris muscle citrate synthase activity in both young (5 mo) and old (23 mo) trained animals (P < 0.05). Computerized densitometric image analysis of fast and slow MHC bands revealed the ratio of fast to slow MHC to be significantly higher (P < 0.005) in the crural compared with costal diaphragm region in both age groups. In addition, a significant age-related increase (P < 0.05) in percentage of slow MHC was observed in both diaphragm regions. However, exercise training failed to change the relative proportion of slow MHC in either the costal or crural region.