Muscle grafts overloaded by ablation of synergistic muscles

We hypothesized that the mass and maximum tetanic tension (Po) of nerve-intact grafts overloaded by ablation of synergistic muscles would be greater than that of standard nerve-intact grafts or of control soleus muscles. Soleus muscles were grafted orthotopically and bilaterally in 35 female rats. Control soleus muscles were obtained from 30 age-matched cohorts. Twenty-eight days following grafting, gastrocnemius muscles were ablated bilaterally in half of the animals. Comparisons were made between 28 and 112 days following grafting. By 112 days the wet mass of the overload nerve-intact grafts was 138% of the standard grafts and 152% of the control soleus muscles, whereas the Po was 161% and 107%, respectively. Specific tension stabilized at approximately 19 +/- 1 N/cm2 for both types of grafts, significantly lower than the value of 24 +/- 1 N/cm2 for control soleus muscles. Ablation of synergistic muscles resulted in a significant and sustained increase in mass and Po in regenerating skeletal muscle autografts. We conclude that provided the appropriate conditioning stimulus small grafts (100-200 mg) are capable of achieving the values for the mass and Po of control muscles.     

Running during recovery from hindlimb suspension induces transient muscle injury

The objectives were to study morphological adaptations of soleus muscle to decreased loading induced by hindlimb suspension and the effect of run training during the subsequent recovery period. Adult female Wistar rats were kept for 28 days with hindlimbs suspended. For the next 28 days, rats were assigned to a cage-sedentary or daily running group. Compared with control soleus muscles, 28 days of hindlimb suspension reduced the mass and fiber cross-sectional area to 58 and 53% of control values, respectively, and decreased type I fibers from 92 +/- 2 to 81 +/- 2%. During recovery, clusters of damaged fibers were observed in the soleus muscle, and this observation was more pronounced in trained animals. Type IIc fibers appeared transiently during recovery, and their presence was exacerbated with training, as IIc fibers increased to approximately 20% of the total by day 14 of recovery and were no longer evident at day 28. Although muscle wet mass does not differ as a result of mode of recovery at day 14, training transiently decreased the overall fiber area compared with sedentary recovery at this point. By day 28 of recovery the morphological characteristics of soleus muscle in the trained group did not differ from control muscle, whereas in the sedentary group muscle mass and overall fiber cross-sectional area were approximately 14% less than control values.     

Adaptations in rat skeletal muscle following long-term resistance exercise training

The purpose of this investigation was to determine whether long-term, heavy resistance training would cause adaptations in rat skeletal muscle structure and function. Ten male Wistar rats (3 weeks old) were trained to climb a 40-cm vertical ladder (4 days/week) while carrying progressively heavier loads secured to their tails. After 26 weeks of training the rats were capable of lifting up to 800 g or 140% of their individual body mass for four sets of 12–15 repetitions per session. No difference in body mass was observed between the trained rats and age-matched sedentary control rats. Absolute and relative heart mass were greater in trained rats than control rats. When expressed relative to body mass, the mass of the extensor digitorum longus (EDL) and soleus muscles was greater in trained rats than control rats. No difference in absolute muscle mass or maximum force-producing capacity was evident in either the EDL or soleus muscles after training, although both muscles exhibited an increased resistance to fatigue. Individual fibre hypertrophy was evident in all four skeletal muscles investigated, i.e. EDL, soleus, plantaris and rectus femoris muscles of trained rats, but muscle fibre type proportions within each of the muscles tested remained unchanged. Despite an increased ability of the rats to lift progressively heavier loads, this heavy resistance training model did not induce gross muscle hypertrophy nor did it increase the force-producing capacity of the EDL or soleus muscles. Accepted: 17 September 1997     

Force deficit during the onset of muscle hypertrophy

The purpose was to study selected structural changes associated with the deficit in maximum specific force (N/cm2) during the early development of skeletal muscle hypertrophy. Ablation of gastrocnemius and plantaris muscles was performed bilaterally in 35-day-old rats (n = 41), and the soleus muscle was studied from days 1 to 30 thereafter. Compared with control muscles from age-matched unoperated rats (n = 48), muscle mass and cross-sectional area increased in parallel from 28 to 52% over the 30-day postoperative period. Specific force of hypertrophied muscle was depressed 38% at days 1 and 3, and by 28% from days 5 to 30 after synergistic muscle ablation compared with age-matched control values. Interstitial space was 38% greater than the control value of 20.4 +/- 1 microliters/100 mg at day 1 only. Protein concentration was depressed 15% for 7 days after the ablation operation, and connective tissue protein concentration was unchanged. The relative magnitude of increased mean fiber cross-sectional area was less than that of muscle mass until day 7 after ablation. Mononuclear cell infiltration in interfascicular spaces occurred from days 3 to 30 without light microscopic evidence of muscle fiber injury. Initial functional deficits are explained in part by an enlarged interstitial space and decreased protein concentration; later deficits are likely accounted for by intracellular changes.     

Glucocorticoid-induced glycogen increases in extensor digitorum longus and soleus grafts in the rat

The purpose of the present study was to compare dexamethasone-induced glycogen increases in normal EDL and SOL muscles with that in free muscle grafts. Glycogen in mature EDL and SOL grafts in the rat equalled control concentrations irrespective of whether the graft was a nerve-intact (NI), nerve-crushed (NC), reimplanted, or cross-transplanted graft. The grafts also possessed the glycogen-regulatory mechanisms to respond to the glucocorticoid dexamethasone (DEX), which increases muscle glycogen. The increase in glycogen induced by DEX in the EDL and SOL grafts resembled that of the EDL and SOL muscles, respectively, whether the grafted muscle was originally an EDL or SOL. DEX induced an approximate twofold increase in glycogen concentration in control muscles and nerve-intact SOL grafts, and a smaller but significant increase in all other free grafts. Nerve crushing prior to grafting resulted in no significant change in muscle weight, glycogen concentration, or DEX-induced glycogen increase in these grafts. The data suggest that skeletal muscle grafts are qualitatively similar to normal muscles in terms of metabolic responsiveness to hormones. Leaving the nerve intact during grafting quantitatively enhances the graft's hormonal sensitivity but the technique of nerve crushing prior to grafting has no such effect.     

Muscle atrophy and hypoplasia with aging: impact of training and food restriction

The purpose of this work is to study the influence of aging, training, and food restriction on skeletal muscle mass and fiber number. Male Fischer 344 rats (n = 49) at 3 mo postpartum were assigned to three groups: 1) sedentary control (confined to cage), 2) exercise trained (18 m/min, 8 degrees grade, 20 min/day, 5 days/wk), or 3) food restricted (alternate days of free access and no access to food). At 12 and 27 mo postpartum the soleus and extensor digitorum longus (EDL) muscles were excised, weighed, and fiber number was quantified after HNO3 digestion. At 27 mo the masses of soleus and EDL muscles of sedentary control rats were 83 and 70%, respectively, of 12-mo values (138 +/- 5 and 151 +/- 4 mg). At 27 mo, soleus muscle mass of trained rats was 113% of sedentary control values, whereas EDL muscle mass was unaffected by training. At 27 mo, food restriction had no effect on the mass of both muscles compared with 27-mo sedentary control values. Fiber number was not affected by training or food restriction in both muscles. Fiber number for soleus and EDL muscles of combined groups declined with age by 5.6 and 4.2%, respectively. With aging, the small loss of muscle fibers can account at most for approximately 25% of the observed skeletal muscle atrophy.     

Exercise training alleviates MCT1 and MCT4 reductions in heart and skeletal muscles of STZ-induced diabetic rats.

We compared the changes in monocarboxylate transporter 1 (MCT1) and 4 (MCT4) proteins in heart and skeletal muscles in sedentary control and streptozotocin (STZ)-induced diabetic rats (3 wk) and in trained (3 wk) control and STZ-induced diabetic animals. In nondiabetic animals, training increased MCT1 in the plantaris (+51%; P < 0.01) but not in the soleus (+9%) or the heart (+14%). MCT4 was increased in the plantaris (+48%; P < 0.01) but not in the soleus muscles of trained nondiabetic animals. In sedentary diabetic animals, MCT1 was reduced in the heart (-30%), and in the plantaris (-31%; P < 0.01) and soleus (-26%) muscles. MCT4 content was also reduced in sedentary diabetic animals in the plantaris (-52%; P < 0.01) and soleus (-25%) muscles. In contrast, in trained diabetic animals, MCT1 and MCT4 in heart and/or muscle were similar to those of sedentary, nondiabetic animals (P > 0.05) but were markedly greater than in the sedentary diabetic animals [MCT1: plantaris +63%, soleus +51%, heart +51% (P > 0.05); MCT4: plantaris +107%, soleus +17% (P > 0.05)]. These studies have shown that 1) with STZ-induced diabetes, MCT1 and MCT4 are reduced in skeletal muscle and/or the heart and 2) exercise training alleviated these diabetes-induced reductions.     

Age effects on myosin subunit and biochemical alterations with skeletal muscle hypertrophy.

The purpose of this study was to determine whether skeletal muscle mass, myofibrillar adenosinetriphosphatase activity, and the expression of myosin heavy (MHC) and light chain subunits are differentially affected in juvenile (4 wk) and young adult (12 wk) rats by a hypertrophic growth stimulus. Hypertrophy of the plantaris or soleus was studied 4 wk after ablation of either two [gastrocnemius (GTN) and soleus or plantaris] or one (GTN) synergistic muscle(s). There was no difference in the relative magnitude of hypertrophy because of age. Plantaris myofibrillar adenosinetriphosphatase activity was decreased 21 and 12% in juvenile and adult rats, respectively, as a result of ablation of both the GTN and soleus. Slow myosin light chain isoforms (1s and 2s) were expressed to a greater extent in hypertrophied plantaris muscles of both ages, but the increase in 1s was greater in juvenile rats. The relative expression of slow beta-MHC in hypertrophied plantaris muscles increased by 470 and 350%, whereas MHC IIb decreased by 70 and 33% in juvenile and adult rats, respectively. The relative expression of MHC IIa increased (56%) in the plantaris after ablation in juvenile rats only. These shifts in myosin subunit expression and the increases in mass were generally about one-half the magnitude when only the GTN was removed. There were no detectable myosin shifts in hypertrophied soleus muscles. Although the extent of muscle hypertrophy is similar, the shifts in myosin subunits were greater in juvenile than in young adult rats.     

Adaptations of skeletal muscle grafts to chronic changes of physical activity

After grafting, many structural and functional characteristics of skeletal muscle change with time until reaching a stable value. For several characteristics, these stable values are less than those observed in control skeletal muscle. Characteristics such as mass and fiber cross-sectional area are influenced by chronic changes in physical activity. The extent of our understanding of the dimensions and mechanisms of activity-induced adaptations of grafts is limited and based solely on experiments with rats. Improvements in mass, protein content, oxidative capacity, and glycogen concentration have been documented with conditioning by running of sufficient intensity and duration. The growth and development of soleus muscle grafts are severely impaired when normal weight-bearing activity is removed. The mass and maximum tension development of grafts are increased with ablation of muscles that function synergistically to the grafts, but are diminished after chronic electrical stimulation. Chronic electrical stimulation does increase oxidative capacity, capillarity, and the resistance to fatigue. Much remains to be learned about the mechanisms by which activity-related adaptations occur in skeletal muscle grafts.     

Response of XIAP, ARC, and FLIP apoptotic suppressors to 8 wk of treadmill running in rat heart and skeletal muscle.

Although it has been demonstrated that exercise training has an antiapoptotic effect on postmitotic myocytes, the mechanisms responsible for this effect are still largely unclear. Because the antiapoptotic effect of exercise training in postmitotic myocytes could be possibly mediated by the upregulation of apoptotic suppressors, this study examined the effect of endurance training on endogenous apoptotic suppressors including X-chromosome-linked inhibitor of apoptosis protein (XIAP), apoptosis repressor with caspases recruitment domain protein (ARC), and FADD-like inhibitor protein (FLIP) in skeletal and cardiac muscles. Eight adult Sprague-Dawley rats were trained 5 days weekly for 8 wk on treadmill, and eight sedentary rats served as controls. Soleus and ventricle muscles were dissected 2 days after the last training session. The mRNA content of XIAP, ARC, and FLIP was estimated by RT-PCR with ribosomal 18S RNA used as an internal control. The protein expression of XIAP, ARC, FLIP(S), and FLIP(alpha) was assessed by Western immunoblot. After training, mRNA content of ARC and FLIP was not different between the control and trained animals, whereas XIAP mRNA content was elevated by 22 and 14% in the trained soleus and cardiac muscles, respectively, relative to the control samples. No difference was found in the protein content of FLIP(S) and FLIP(alpha) between control and trained muscles, whereas XIAP and ARC protein content was increased by 18 and 38%, respectively, in the soleus muscle of trained animals. Furthermore, negative relationships were found between XIAP and apoptotic DNA fragmentation as well as ARC and caspase-3 activity. These findings are consistent with the hypothesis that the modulation of apoptotic suppressors is involved in training-induced attenuation of apoptosis in skeletal and cardiac muscles.     

Adaptive response of hypertrophied skeletal muscle to endurance training

The response of hypertrophied soleus and plantaris muscle of rats to endurance training was studied. Hypertrophy was produced by bilateral extirpation of the gastrocnemius muscle. A 13-wk training program of treadmill running initiated 30 days after removal of the gastrocnemius muscle accentuated (P less than 0.01) the hypertrophy. Succinate dehydrogenase activities of the enlarged muscles of sedentary rats were similar to those of normal animals, as were the increases associated with training. Phosphorylase and hexokinase activities were unaltered as a result of the experimental perturbations. Rates of glycogen depletion during exercise were lower (P less than 0.01) in the liver and soleus and plantaris muscles of endurance-trained animals. No difference existed in the rate of glycogen depletion of normal and hypertrophied muscle within the sedentary or trained groups. These data demonstrate that extensively hypertrophied muscle responds to training and exercise in a manner similar to that of normal muscle.     

Skeletal muscle glucose uptake following overload-induced hypertrophy.

While endurance exercise training has been shown to enhance insulin action in skeletal muscle, the effects of high resistance strength training are less clear. The purpose of this study was to determine the rate of glucose uptake in skeletal muscle in which compensatory hypertrophy was induced by synergist muscle ablation. Basal and insulin mediated [3H] 2-deoxyglucose uptake were measured in soleus and EDL muscles using the perfused rat hindquarter preparation. Neither basal nor insulin mediated glucose uptake, when expressed per gram muscle, were enhanced in hypertrophied soleus muscles compared with control muscles, despite a twofold increase in mass (P less than 0.01). In the EDL, muscle mass increased 60% with synergist ablation (P less than 0.01), however insulin mediated glucose uptake was not different from that of control muscles. The basal rate of glucose uptake in hypertrophied EDL muscles was increased twofold over that of control muscles (P less than 0.05), possibly due to changes in neural input and/or loading. These results suggest that the stimulus for development of increased muscle mass is different from that for metabolic adaptations.     

Age- and training-related changes in the collagen metabolism of rat skeletal muscle

The effects of ageing and life-long endurance training on the collagen metabolism of skeletal muscle were evaluated in a longitudinal study. Wistar rats performed treadmill running 5 days a week for 2 years. The activities of collagen biosynthesis enzymes, prolyl-4-hydroxylase and galactosylhydroxylysyl glucosyltransferase, were highest in the muscles of the youngest animals, decreased up to the age of 2 months and from then on remained virtually unchanged. The enzyme activity in young animals was higher in the slow collagenous soleus muscle than in the rectus femoris muscle. The enzyme activity in the soleus muscle was higher for older trained rats than older untrained rats. The relative proportion of type I collagen increased and that of type III collagen decreased with age, suggesting a more marked contribution by type I collagen to the age-related accumulation of total muscular collagen. The results show that collagen biosynthesis decreases with maturation and that life-long endurance training maintains a higher level of biosynthesis in slow muscles.     

Mechanical deficit persists during long-term muscle hypertrophy

Hypotheses were tested that the deficit in maximum isometric force normalized to muscle cross-sectional area (i.e., specific Po, N/cm2) of hypertrophied muscle would return to control value with time and that the rate and magnitude of adaptation of specific force would not differ between soleus and plantaris muscles. Ablation operations of the gastrocnemius and plantaris muscles or the gastrocnemius and soleus muscles were done to induce hypertrophy of synergistic muscle left intact in female Wistar rats (n = 47) at 5 wk of age. The hypertrophied soleus and plantaris muscles and control muscles from other age-matched rats (n = 22) were studied from days 30 to 240 thereafter. Po was measured in vitro at 25 degrees C in oxygenated Krebs-Ringer bicarbonate. Compared with control values, soleus muscle cross-sectional area increased 41-15% from days 30 to 240 after ablation, whereas Po increased 11 and 15% only at days 60 and 90. Compared with control values, plantaris muscle cross-sectional area increased 52% at day 30, 40% from days 60 through 120, and 15% at day 240. Plantaris muscle Po increased 25% from days 30 to 120 but at day 240 was not different from control value. Changes in muscle architecture were negligible after ablation in both muscles. Specific Po was depressed from 11 to 28% for both muscles at all times. At no time after the ablation of synergistic muscle did the increased muscle cross-sectional area contribute fully to isometric force production.     

Effect of resistance exercise training on expression of Hsp70 and inflammatory cytokines in skeletal muscle and adipose tissue of STZ-induced diabetic rats

Impairment of adipose tissue and skeletal muscles accrued following type 1 diabetes is associated with protein misfolding and loss of adipose mass and skeletal muscle atrophy. Resistance training can maintain muscle mass by changing both inflammatory cytokines and stress factors in adipose tissue and skeletal muscle. The purpose of this study was to determine the effects of a 5-week ladder climbing resistance training program on the expression of Hsp70 and inflammatory cytokines in adipose tissue and fast-twitch flexor hallucis longus (FHL) and slow-twitch soleus muscles in healthy and streptozotocin-induced diabetic rats. Induction of diabetes reduced body mass, while resistance training preserved FHL muscle weight in diabetic rats without any changes in body mass. Diabetes increased Hsp70 protein content in skeletal muscles, adipose tissue, and serum. Hsp70 protein levels were decreased in normal and diabetic rats by resistance training in the FHL, but not soleus muscle. Furthermore, resistance training decreased inflammatory cytokines in FHL skeletal muscle. On the other hand, Hsp70 and inflammatory cytokine protein levels were increased by training in adipose tissue. Also, significant positive correlations between inflammatory cytokines in adipose tissue and skeletal muscles with Hsp70 protein levels were observed. In conclusion, we found that in diabetic rats, resistance training decreased inflammatory cytokines and Hsp70 protein levels in fast skeletal muscle, increased adipose tissue inflammatory cytokines and Hsp70, and preserved FHL muscle mass. These results suggest that resistance training can maintain skeletal muscle mass in diabetes by changing inflammatory cytokines and stress factors such as Hsp70 in skeletal muscle and adipose tissue.     

The effect of creatine supplementation on mass and performance of rat skeletal muscle

This study investigated the effect of dietary creatine supplementation on hypertrophy and performance of rat skeletal muscle. Male Sprague-Dawley rats underwent either tibialis anterior ablation or partial ablation of the plantaris/gastrocnemius to induce compensatory hypertrophy of the extensor digitorum longus (EDL) or soleus respectively, or sham surgery. Creatine (300 mg/kg) was administered to one half of each group for 5 weeks, after which force production was measured. With the leg fixed at the knee and ankle, the distal tendon of the EDL or soleus was attached to a force transducer and the muscle was electrically stimulated via the sciatic nerve. Synergist ablation resulted in a significant increase in EDL mass and in soleus mass relative to control muscles. However, no effect of creatine supplementation on muscle mass or performance was found between control and either group of creatine-treated rats. Despite an apparent increase in muscle creatine content, creatine supplementation did not augment muscle hypertrophy or force production in rat EDL or soleus muscle, providing evidence that the potential benefits of creatine supplementation are not due to a direct effect on muscle but rather to an enhanced ability to train.     

Effect of training on skeletal muscle injury from downhill running in rats

Experiments were conducted to test the hypothesis that injury to skeletal muscle in rats resulting from prolonged downhill running is prevented to a greater extent by prior downhill training than by either uphill or level training. Changes in plasma creatine phosphokinase (CPK) activity and glucose-6-phosphate dehydrogenase (G-6-PDase) activity in the soleus (S), vastus intermedius (VI), and medial head of triceps brachii (TM) muscles were evaluated as markers of muscle injury 48 h after 90 min of intermittent downhill running (16 m . min -1). Prior to this acute downhill run, groups of rats were trained by either downhill (-16 degrees), level (0 degrees), or uphill (+16 degrees) running (16 m . min -1) for 30 min/day. Training duration was either 5 days or 1 day. A training effect (i.e., reduced muscle injury) was indicated if muscle G-6-PDase or plasma CPK activity in a trained group following the 90-min downhill run was not different from that of nonexercised control animals and/or if it was lower than that of nontrained runners. A significant training effect was achieved in all three muscles with 5 days of either downhill or level training, but only in S after 5 days of uphill training. Elevation of plasma CPK activity was prevented by 5 days of training on all three inclines.(ABSTRACT TRUNCATED AT 250 WORDS)     

Modulation of insulin resistance and hypertension by voluntary exercise training in the TG(mREN2)27 rat.

Hypertension is often accompanied by insulin resistance of skeletal muscle glucose transport. The male heterozygous TG(mREN2)27 rat, which harbors a mouse transgene for renin, displays local elevations in the renin-angiotensin system and exhibits markedly elevated systolic blood pressure (SBP). The present study was undertaken to characterize insulin-stimulated skeletal muscle glucose transport in male heterozygous TG(mREN2)27 rats and to evaluate the effect of voluntary exercise training on SBP and skeletal muscle glucose transport. Compared with normotensive Sprague-Dawley rats, TG(mREN2)27 rats displayed a 53% elevation (P < 0.05) in SBP, a twofold increase in plasma free fatty acid levels, and an exaggerated insulin response during an oral glucose tolerance test. Moreover, insulin-mediated glucose transport (2-deoxyglucose uptake) in isolated epitrochlearis and soleus muscles of TG(mREN2)27 animals was 33 and 43% less, respectively, than in Sprague-Dawley controls. TG(mREN2)27 rats ran voluntarily for 6 wk and achieved daily running distances of 6-7 km over the final 3 wk. Training caused a 36% increase in peak aerobic capacity and a 16% reduction in resting SBP. Fasting plasma insulin (21%) and free fatty acid (34%) levels were reduced in the trained TG(mREN2)27 rats. Whole body glucose tolerance was improved in the trained TG(mREN2)27 rats and was associated with increases of 39 and 50% in insulin-mediated glucose transport in epitrochlearis and soleus muscles, respectively. Whole muscle GLUT-4 protein was increased in the soleus (23%), but not in the epitrochlearis, of trained TG(mREN2)27 rats. These data indicate that the male heterozygous TG(mREN2)27 rat is a model of both hypertension and insulin resistance. Importantly, both of these defects can be beneficially modified by voluntary exercise training.     

Exercise-induced adaptations of rat soleus muscle grafts

In female Wistar rats (n = 316) under pentobarbital sodium anesthesia, the soleus muscle was autografted with its nerve reimplanted. One purpose was to characterize the chronological development of graft innervation and recruitment during locomotion. Furthermore, we tested hypotheses regarding the efficacy of run conditioning of different intensities, durations, and postgrafting initiation times to alter mass and pyruvate-malate oxidation capacity of grafts. Choline acetyltransferase activity of grafts increased from 10% of control value at 7 days postgrafting to 55 and 100% at days 28 and 56, respectively. Running-induced glycogen depletion occurred in grafts; this is consistent with graft recruitment during locomotion. There was a threshold of conditioning intensity below which no improvements occurred and above which there were improvements. Spring (50 m/min) and endurance (30 m/min) conditioning of a duration of at least 28 days that was initiated at 28 or 56 days postgrafting increased mass of grafts by 30% compared with grafts from nonconditioned rats. Easy conditioning (15 m/min) had no effect on graft mass. Changes in graft total protein content paralleled those of mass. Oxidation capacity of grafts increased significantly with some conditioning protocols, but not to the same extent as mass. The exercise-induced adaptations should improve graft function in the host organism.     

Angiotensin-converting enzyme inhibition attenuates myonuclear addition in overloaded slow-twitch skeletal muscle

Because optimal overload-induced skeletal muscle hypertrophy requires ANG II, we aimed to determine the effects of blocking ANG II production [via angiotensin-converting enzyme (ACE) inhibition] on potential mediators of hypertrophy in overloaded skeletal muscle, namely, myonuclear addition and fibroblast content. In a 2 x 2 design, adult (200-225 g) female Sprague-Dawley rats were placed into one of four groups (n = 8/group): 7-day skeletal muscle overload, sham operation, 7-day skeletal muscle overload with ACE inhibition, or sham operation with ACE inhibition. Functional overloads of the plantaris and soleus muscles were produced via bilateral surgical ablation of the synergistic gastrocnemius muscle, and ACE inhibition was accomplished by the addition of the ACE inhibitor enalapril maleate to the animals' daily drinking water (0.3 mg/ml). Myonuclear addition and extrasarcolemmal nuclear proliferation, as measured by in vivo 5-bromo-2'-deoxyuridine labeling, were significantly (P < or = 0.05) increased by overload in both the slow-twitch soleus and fast-twitch plantaris muscles. Furthermore, ACE inhibition attenuated these overload-induced increases in the soleus muscle but not in the plantaris muscle. However, the effect of ACE inhibition on soleus extrasarcolemmal nuclei was not likely due to differences in fibroblast content because overload elicited significant increases in vimentin-positive areas in soleus and plantaris muscles, and these areas were unaffected by ACE inhibition in either muscle. There was no effect of ACE inhibition on any measure in sham-operated muscles. Collectively, these data indicate that ANG II may mediate the satellite cell response to overload in slow-twitch soleus but not in fast-twitch plantaris muscles and that this effect may occur independently of changes in fibroblast content.