Plasticity in Skeletal, Cardiac, and Smooth Muscle: Selected Contribution: IGF-I antibody prevents increases in protein synthesis in epitrochlearis muscles from refed, diabetic rats

The purpose of this study was to examine whether immune neutralizationof muscle-produced insulin-like growth factor I (IGF-I) would preventan appropriate anabolic response to refeeding in diabetic rats. MaleSprague-Dawley rats were made diabetic by partial pancreatectomy andwere randomly assigned to be either control-fed, fasted, orfasted-refed (n = 7-8 per group). Diabetes decreased rates of protein synthesis and increased rates of protein degradation in incubated epitrochlearis muscles (P < 0.05). In both groups of rats, fasting lowered protein synthesis andincreased proteolysis and subsequent refeeding returned both parameters to near basal values (P < 0.05). Neutralization ofmuscle IGF-I by the addition of IGF-I antibody to the incubation mediumreduced protein synthesis an average of 22% for all groups(P < 0.05). However, rates of protein degradation werenot affected. In nondiabetic rats, refeeding increased proteinsynthesis in both control and antibody-treated muscles(P < 0.05). Refeeding also increased protein synthesisin the control muscles from diabetic rats (P < 0.01).In contrast, muscles from diabetic rats that were incubated withanti-IGF-I did not increase protein synthesis in response to refeeding.These data suggest that immune neutralization of muscle IGF-I inhypoinsulinemic rats negated the ability of endogenous IGF-I to promoteprotein synthesis and thereby prevented an appropriate anabolic response.

     

The relationships among IGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy

Adams, G. R., and F. Haddad. The relationships amongIGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy. J. Appl. Physiol. 81(6):2509-2516, 1996.Insulin-like growth factor-1 (IGF-1) is known tohave anabolic effects on skeletal muscle cells. This study examined thetime course of muscle hypertrophy and associated IGF-1 peptide and mRNAexpression. Data were collected at 3, 7, 14, and 28 days after surgicalremoval of synergistic muscles of both normal and hypophysectomized(HX) animals. Overloading increased the plantaris (Plant) mass,myofiber size, and protein-to-body weight ratio in both groups (normaland HX; P < 0.05). Muscle IGF-1peptide levels peaked at 3 (normal) and 7 (HX) days of overloading withmaximum 4.1-fold (normal) and 6.2-fold (HX) increases. Increases inmuscle IGF-1 preceded the hypertrophic response. Total DNA content ofthe overloaded Plant increased in both groups. There was a strongpositive relationship between IGF-1 peptide and DNA content in theoverloaded Plant from both groups. These results indicate that1) the muscles from rats with bothnormal and severely depressed systemic levels of IGF-1 respond tofunctional overload with an increase in local IGF-1 expression and2) this elevated IGF-1 may becontributing to the hypertrophy response, possibly via the mobilizationof satellite cells to provide increases in muscle DNA.

     

Phosphorylation of p70S6k correlates with increased skeletal muscle mass following resistance exercise

High-resistance exercise training results in an increase inmuscle wet mass and protein content. To begin to address the acute changes following a single bout of high-resistance exercise, a newmodel has been developed. Training rats twice a week for 6 wk resultedin 13.9 and 14.4% hypertrophy in the extensor digitorum longus (EDL)and tibialis anterior (TA) muscles, respectively. Polysome profilesafter high-resistance lengthening contractions suggest that the rate ofinitiation is increased. The activity of the 70-kDa S6 protein kinase(p70^S6k), a regulator oftranslation initiation, is also increased following high-resistancelengthening contractions (TA, 363 ± 29%; EDL, 353 ± 39%).Furthermore, the increase inp70^S6k activity 6 h after exercisecorrelates with the percent change in muscle mass after 6 wk oftraining (r = 0.998). The tightcorrelation between the activation ofp70^S6k and the long-term increasein muscle mass suggests thatp70^S6k phosphorylation may be agood marker for the phenotypic changes that characterize musclehypertrophy and may play a role in load-induced skeletal muscle growth.

     

Muscle adaptations to hindlimb suspension in mature and old Fischer 344rats

Stump, Craig S., Charles M. Tipton, and Erik J. Henriksen.Muscle adaptations to hindlimb suspension in mature and oldFischer 344 rats. J. Appl. Physiol.82(6): 1875-1881, 1997.We examined skeletal and cardiac muscleresponses of mature (8 mo) and old (23 mo) male Fischer 344 rats to 14 days of hindlimb suspension. Hexokinase (HK) and citrate synthase (CS)activities and GLUT-4 glucose transporter protein level, which arecoregulated in many instances of altered neuromuscular activity, wereanalyzed in soleus (Sol), plantaris (Pl), tibialis anterior (TA),extensor digitorum longus (EDL), and left ventricle. Protein contentwas significantly (P < 0.05) lowerin all four hindlimb muscles after suspension compared with controls inboth mature (21-44%) and old (17-43%) rats. Old ratsexhibited significantly lower CS activities than mature rats for theSol, Pl, and TA. HK activities were significantly lower in the old ratsfor the Pl (19%) and TA (33%), and GLUT-4 levels were lower in theold rats for the TA (38%) and EDL (24%) compared with the maturerats. Old age was also associated with a decrease in CS activity (12%)and an increase in HK activity (14%) in cardiac muscle. CS activitieswere lower in the Sol (20%) and EDL (18%) muscles from maturesuspended rats and in the Sol (25%), Pl (27%), and EDL (25%) musclesfrom old suspended rats compared with corresponding controls. However,suspension was associated with significantly higher HK activities forall four hindlimb muscles examined, in both old (16-57%) andmature (10-43%) rats, and higher GLUT-4 concentrations in the TAmuscles of the old rats (68%) but not the mature rats. These resultsindicate that old age is associated with decreased CS and HK activities and GLUT-4 protein concentration for several rat hindlimb muscles, andthese variables are not coregulated during suspension. Finally, old ratskeletal muscle appears to respond to suspension to a similar orgreater degree than mature rat muscle responds.

     

Differential respiratory muscle recruitment induced by clonidine in awake goats

The purpose of this study was to test thehypothesis that dysrhythmic breathing induced by the₂-agonist clonidine isaccompanied by differential recruitment of respiratory muscles. Inadult goats (n = 14) electromyographic(EMG) measurements were made from inspiratory muscles (diaphragm andparasternal intercostal) and expiratory muscles [triangularissterni (TS) and transversus abdominis (Abd)]. EMG of thethyroarytenoid (TA) muscle was used as an index of upper airway(glottal) patency. Peak EMG activities of all spinal inspiratory andexpiratory muscles were augmented by central and peripheralchemoreceptor stimuli. Phasic TA was apparent in the postinspiratoryphase of the breathing cycle under normoxic conditions. Duringdysrhythmic breathing episodes induced by clonidine, TS and Abdactivities were attenuated or abolished, whereas diaphragm andparasternal intercostal activities were unchanged. There was no tonicactivation of TS or Abd EMG during apneas; however, TA activity becametonic throughout the apnea. We conclude that1) ₂-adrenoceptor stimulationresults in differential recruitment of respiratory muscles duringrespiratory dysrhythmias and 2) apneas are accompanied by active glottic closure in the awake goat.

     

Mechanisms leading to restoration of muscle size with exercise and transplantation after spinal cord injury

We have shown thatcycling exercise combined with fetal spinal cord transplantationrestored muscle mass reduced as a result of complete transection of thespinal cord. In this study, mechanisms whereby this combinedintervention increased the size of atrophied soleus and plantarismuscles were investigated. Rats were divided into five groups(n = 4, per group): control, nontransected; spinal cordtransected at T10 for 8 wk (Tx); spinal cord transected for 8 wk andexercised for the last 4 wk (TxEx); spinal cord transected for 8 wkwith transplantation of fetal spinal cord tissue into the lesion site 4 wk prior to death (TxTp); and spinal cord transected for 8 wk,exercised for the last 4 wk combined with transplantation 4 wk prior todeath (TxExTp). Tx soleus and plantaris muscles were decreased in sizecompared with control. Exercise and transplantation alone did notrestore muscle size in soleus, but exercise alone minimized atrophy inplantaris. However, the combination of exercise and transplantationresulted in a significant increase in muscle size in soleus andplantaris compared with transection alone. Furthermore, myofibernuclear number of soleus was decreased by 40% in Tx and was notaffected in TxEx or TxTp but was restored in TxExTp. A strongcorrelation (r = 0.85) between myofiber cross-sectional area and myofiber nuclear number was observed in soleus, but not inplantaris muscle, in which myonuclear number did not change with any ofthe experimental manipulations. 5'-Bromo-2'-deoxyuridine-positive nuclei inside the myofiber membrane were observed in TxExTp soleus muscles, indicating that satellite cells had divided and subsequently fused into myofibers, contributing to the increase in myonuclear number. The increase in satellite cell activity did not appear to becontrolled by the insulin-like growth factors (IGF), as IGF-I andIGF-II mRNA abundance was decreased in Tx soleus and plantaris, and wasnot restored with the interventions. These results indicate that,following a relatively long postinjury interval, exercise andtransplantation combined restore muscle size. Satellite cell fusion andrestoration of myofiber nuclear number contributed to increased musclesize in the soleus, but not in plantaris, suggesting that cellularmechanisms regulating muscle size differ between muscles with differentfiber type composition.

     

Modulation of myosin isoform expression by mechanical loading: role of stimulation frequency

Caiozzo, Vincent J., Michael J. Baker, and Kenneth M. Baldwin. Modulation of myosin isoform expression by mechanical loading: role of stimulation frequency. J. Appl.Physiol. 82(1): 211-218, 1997.This study testedthe hypothesis that mechanical loading, not stimulation frequency perse, plays a key role in determining the plasticity of myosin heavychain (MHC) protein isoform expression in muscle undergoing resistancetraining. Female Sprague-Dawley rats were randomly assigned toresistance-training programs that employed active1) shortening(n = 7) or2) lengthening contractions(n = 8). The medial gastrocnemius (MG)muscles in each group trained under loading conditions thatapproximated 90-95% of maximum isometric tetanictension but were stimulated at frequencies of 100 and~25 Hz, respectively. Lengthening and shortening contractions wereproduced by using a Cambridge ergometer system. The MG muscles trainedevery other day, performing a total of 16 training sessions. Bothtraining programs produced significant (P < 0.01) and similar reductions inthe fast type IIB MHC protein isoform in the white MG muscle, reducingits relative content to ~50% of the total MHC protein isoform pool.These changes were accompanied by increases in the relative content ofthe fast type IIX MHC protein isoform that were of similar magnitudefor both groups. The results of this study clearly demonstrate thatstimulation frequency does not play a key role in modulating MHCisoform alterations that result from high-resistance training.

     

Voluntary exercise training enhances glucose transport in muscle stimulated by insulin-like growth factor I

Hokama, Jason Y., Ryan S. Streeper, and Erik J. Henriksen.Voluntary exercise training enhances glucose transport in muscle stimulated by insulin-like growth factor I. J. Appl. Physiol. 82(2): 508-512, 1997.Skeletal muscle glucosetransport can be regulated by hormonal factors such as insulin andinsulin-like growth factor I (IGF-I). Although it is well establishedthat exercise training increases insulin action on muscle glucosetransport, it is currently unknown whether exercise training leads toan enhancement of IGF-I-stimulated glucose transport in skeletal muscle. Therefore, we measured glucose transport activity [by using 2-deoxy-D-glucose (2-DG)uptake] in the isolated rat epitrochlearis muscle stimulated bysubmaximally and maximally effective concentrations of insulin (0.2 and13.3 nM) or IGF-I (5 and 50 nM) after 1, 2, and 3 wk of voluntary wheelrunning (WR). After 1 wk of WR, both submaximal andmaximal insulin-stimulated 2-DG uptake rates were significantly(P < 0.05) enhanced (43 and 31%)compared with those of sedentary controls, and these variables werefurther increased after 2 (86 and 57%) and 3 wk (71 and 70%) ofWR. Submaximal and maximal IGF-I-stimulated 2-DG uptakerates were significantly enhanced after 1 wk of WR (82 and 61%), andthese increases did not expand substantially after 2 (71 and 58%) and3 wk (96 and 70%) of WR. This enhancement of hormone-stimulated 2-DGuptake in WR muscles preceded any alteration in glucose transporter(GLUT-4) protein level, which increased only after 2 (24%) and 3 wk(54%) of WR. Increases in GLUT-4 protein were significantly correlated (r = 0.844) with increases in citratesynthase. These results indicate that exercise training can enhanceboth insulin-stimulated and IGF-I-stimulated muscle glucose transportactivity and that these improvements can develop without an increase inGLUT-4 protein.

     

Glucose transporter content and enzymes of metabolism in nerve-repair grafted muscle of aging Fischer 344rats

Larkin, Lisa, Eric R. Leiendecker, Mark Supiano, and JeffreyHalter. Glucose transporter content and enzymes of metabolism innerve-repair grafted muscle of aging Fischer 344 rats.J. Appl. Physiol. 83(5):1623-1629, 1997.Aging and grafting are associated with decreasedability of muscle to sustain power, likely reflecting diminished fuelavailability. To assess mechanisms that may contribute to availabilityof glucose, we studied GLUT-1 and GLUT-4 protein as well as mRNAcontents and enzymes of glucose metabolism in grafted and controlmedial gastrocnemius (MG) muscles of 6-, 12-, and24-mo-old male Fischer 344 rats. There was no effect of age or graftingon MG GLUT-4 content. There was both an age- and graft-associated increase in GLUT-1 content (P = 0.0044 and 0.0063, respectively). There was no effect of aging or grafting onhexokinase and phosphofructokinase activity or on protein and glycogencontent. Muscle mass and citrate synthase activity were significantlydiminished with grafting. Citrate synthase activity was significantlygreater in the 12-mo-old compared with the 6- and 24-mo-old animals.Grafting in combination with aging had no impact on any of theparameters measured. We conclude that diminished glucose transporterexpression cannot explain the decreased ability of aged muscle tosustain power. In addition, we conclude that the diminished ability ofthe grafted MG muscle to sustain power may be explained, in part, by adecrease in energy available from oxidative metabolism.

     

Decreased insulin action on muscle glucose transport after eccentric contractions in rats

Asp, Sven, and Erik A. Richter. Decreased insulinaction on muscle glucose transport after eccentric contractions in rats. J. Appl. Physiol. 81(5):1924-1928, 1996.We have recently shown that eccentriccontractions (Ecc) of rat calf muscles cause muscle damage anddecreased glycogen and glucose transporter GLUT-4 protein content inthe white (WG) and red gastrocnemius (RG) but not in the soleus (S) (S. Asp, S. Kristiansen, and E. A. Richter. J. Appl.Physiol. 79: 1338-1345, 1995). To study whetherthese changes affect insulin action, hindlimbs were perfused at three different insulin concentrations (0, 200, and 20,000 µU/ml) 2 daysafter one-legged eccentric contractions of the calf muscles. Comparedwith control, basal glucose transport was slightly higher (P < 0.05) in Ecc-WG and -RG,whereas it was lower (P < 0.05) atboth submaximal and maximal insulin concentrations in the Ecc-WG and atmaximal concentrations in the Ecc-RG. In the Ecc-S, the glucosetransport was unchanged in hindquarters perfused in the absence orpresence of a submaximal stimulating concentration of insulin, whereasit was slightly (P < 0.05) higherduring maximal insulin stimulation compared with control S. At the endof perfusion the glycogen concentrations were lower in bothEcc-gastrocnemius muscles compared with control muscles at all insulinconcentrations. Fractional velocity of glycogen synthase increasedsimilarly with increasing insulin concentrations in Ecc- and control WGand RG. We conclude that insulin action on glucose transport but notglycogen synthase activity is impaired in perfused muscle exposed toprior eccentric contractions.

     

Differential effects of long-term leucine infusion on tissue protein synthesis in neonatal pigs

Leucine is unique among the amino acids in its ability to promote protein synthesis by activating translation initiation via the mammalian target of rapamycin (mTOR) pathway. Previously, we showed that leucine infusion acutely stimulates protein synthesis in fast-twitch glycolytic muscle of neonatal pigs but this response cannot be maintained unless the leucine-induced fall in amino acids is prevented. To determine whether leucine can stimulate protein synthesis in muscles of different fiber types and in visceral tissues of the neonate in the long-term if baseline amino acid concentrations are maintained, overnight fasted neonatal pigs were infused for 24 h with saline, leucine (400 μmol kg⁻¹ h⁻¹), or leucine with replacement amino acids to prevent the leucine-induced hypoaminoacidemia. Changes in the fractional rate of protein synthesis and activation of mTOR, as determined by eukaryotic initiation factor 4E binding protein (4E-BP1) and S6 kinase 1 (S6K1) phosphorylation, in the gastrocnemius and masseter muscles, heart, liver, jejunum, kidney, and pancreas were measured. Leucine increased mTOR activation in the gastrocnemius and masseter muscles, liver, and pancreas, in both the absence and presence of amino acid replacement. However, protein synthesis in these tissues was increased only when amino acids were infused to maintain baseline levels. There were no changes in mTOR signaling or protein synthesis in the other tissues we examined. Thus, long-term infusion of leucine stimulates mTOR signaling in skeletal muscle and some visceral tissues but the leucine-induced stimulation of protein synthesis in these tissues requires sustained amino acid availability.     

Changes in insulin-stimulated glucose transport and GLUT-4 protein in rat skeletal muscle after training

Kawanaka, Kentaro, Izumi Tabata, Shigeru Katsuta, andMitsuru Higuchi. Changes in insulin-stimulated glucose transport and GLUT-4 protein in rat skeletal muscle after training.J. Appl. Physiol. 83(6):2043-2047, 1997.After running training, which increased GLUT-4protein content in rat skeletal muscle by <40% compared with controlrats, the training effect on insulin-stimulated maximal glucosetransport (insulin responsiveness) in skeletal muscle was short lived(24 h). A recent study reported that GLUT-4 protein content in ratepitrochlearis muscle increased dramatically (~2-fold) after swimmingtraining (J.-M. Ren, C. F. Semenkovich, E. A. Gulve, J. Gao, andJ. O. Holloszy. J. Biol.Chem. 269, 14396-14401, 1994).Because GLUT-4 protein content is known to be closely related toskeletal muscle insulin responsiveness, we thought it possible that thetraining effect on insulin responsiveness may remain for >24 h afterswimming training if GLUT-4 protein content decreases gradually fromthe relatively high level and still remains higher than control levelfor >24 h after swimming training. Therefore, we examined thispossibility. Male Sprague-Dawley rats swam 2 h a day for 5 days with aweight equal to 2% of body mass. Approximately 18, 42, and 90 h aftercessation of training, GLUT-4 protein concentration and2-[1,2-³H]deoxy-D-glucosetransport in the presence of a maximally stimulating concentration ofinsulin (2 mU/ml) were examined by using incubated epitrochlearismuscle preparation. Swimming training increased GLUT-4 proteinconcentration and insulin responsiveness by 87 and 85%, respectively,relative to age-matched controls when examined 18 h after training.Forty-two hours after training, GLUT-4 protein concentration andinsulin responsiveness were still higher by 52 and 51%, respectively,in muscle from trained rats compared with control. GLUT-4 proteinconcentration and insulin responsiveness in trained muscle returned tosedentary control level within 90 h after training. We conclude that1) the change in insulinresponsiveness during detraining is directly related to muscle GLUT-4protein content, and 2)consequently, the greater the increase in GLUT-4 protein content thatis induced by training, the longer an effect on insulin responsivenesspersists after the training.

     

Changes in satellite cell content and myosin isoforms in low-frequency-stimulated fast muscle of hypothyroid rat

Chroniclow-frequency stimulation was used to study the effects of enhancedcontractile activity on satellite cell content and myosin isoformexpression in extensor digitorum longus muscles from hypothyroid rats.As verified by immunohistochemical staining for desmin, vimentin, andmyosin heavy chain (MHC) isoforms and by histological analysis,stimulation induced a transformation of existing fast fibers towardslower fibers without signs of fiber deterioration or regeneration.Immunohistochemically detected increases in MHC I and MHC IIa isoforms,as well as reduced numbers of fibers expressing the faster MHCisoforms, mirrored the rearrangement of the thick-filament composition.These changes, especially the upregulation of MHC IIa, were accompaniedby an induction of developmental MHC isoforms in the transforming adultfibers. Satellite cell content rose 2.6-, 3.0-, and 3.7-fold over thatof corresponding controls (P < 0.05 in all cases) in 5-, 10-, and 20-day-stimulated muscles, respectively.Hypothyroidism alone had no effect on satellite cell content butresulted in a significant reduction in fiber size. The relativesatellite cell contents increased (P < 0.05) from 3.8% in euthyroid control muscles to 7.9, 11.5, and13.8% in the 5-, 10-, and 20-day-stimulated hypothyroid muscles,respectively. In 20-day-stimulated muscles, the relative satellite cellcontent reached an almost twofold higher level than that of normalslow-twitch soleus muscle. This increase occurred concomitantly with arise in myonuclear density, most probably because of the fusion of satellite cells with existing fibers.

     

Effect of insulin-like growth factor I and/or growth hormone on diaphragm of malnourished adolescent rats

Lewis, Michael I., Thomas J. LoRusso, and Mario Fournier.Effect of insulin-like growth factor I and/or growthhormone on diaphragm of malnourished adolescent rats.J. Appl. Physiol. 82(4):1064-1070, 1997.Young growing animals appear to havesignificantly reduced "nutritional reserve" to short periods ofunstressed starvation compared with adults, with resultant growtharrest and/or atrophy of diaphragm (Dia) muscle fibers. The aimof this study was to assess in an adolescent rat model of acutenutritional deprivation (ND; 72 h) the impact of insulin-like growthfactor I (IGF-I), with or without added growth hormone (GH), on thecross-sectional areas (CSA) of individual Dia muscle fibers. Fivegroups were studied: 1) control(Ctr); 2) ND;3) ND given IGF-I (ND/IGF-I); 4) ND given GH (ND/GH); and5) ND given a combination of IGF-I and GH (ND/IGF-I/GH). IGF-I was given by a subcutaneously implanted osmotic minipump (200 µg/day), whereas GH was administered twice daily by a subcutaneous injection (250 µg every 12 h). Isometric contractile and fatigue properties of the Dia were determined in vitro.Forces were normalized for muscle CSA (i.e., specific force). Dia fibertype proportions were determined histochemically, and fiber CSA wasquantified by using a computer-based image-processing system. Totalserum IGF-I concentrations were significantly reduced in ND and ND/GHanimals, compared with Ctr, and elevated in the groups receiving IGF-I.The provision of growth factors did not alter the contractile orfatigue properties of ND animals. Dia fiber type proportions weresimilar among the groups. In ND animals, there was a significantreduction in the CSA of types I, IIa, IIx, and IIc Dia fibers comparedwith Ctr. The administration of IGF-I alone or in combination with GHto ND animals significantly diminished the reduction in Dia fiber size.GH alone had no effect on Dia fiber size in ND animals. We concludethat with acute ND the peripheral resistance to the action of GHappears to be bypassed by the administration of IGF-I alone or incombination with GH.

     

Enhanced muscle glucose uptake facilitates nitrogen efflux from exercised muscle

The hypothesis that glucose ingestion inthe postexercise state enhances the synthesis of glutamine and alaninein the skeletal muscle was tested. Glucose was infused intraduodenallyfor 150 min (44.5 µmol · kg¹ · min¹)beginning 30 min after a 150-min period of exercise(n = 7) or an equivalent durationsedentary period (n = 10) in18-h-fasted dogs. Prior exercise caused a twofold greater increase inlimb glucose uptake during the intraduodenal glucose infusion compared with uptake in sedentary dogs. Arterial glutamine levels fell graduallywith the glucose load in both groups. Net hindlimb glutamine effluxincreased in response to intraduodenal glucose in exercised but notsedentary dogs (P < 0.05-0.01).Arterial alanine levels, depleted by 50% with exercise, rose withintraduodenal glucose in exercised but not sedentary dogs(P < 0.05-0.01). Net hindlimb alanine efflux also rose in exercised dogs in response to intraduodenal glucose (P < 0.05-0.01),whereas it was not different from baseline in sedentary controls forthe first 90 min of glucose infusion. Beyond this point,it, too, rose significantly. We conclude that oral glucosemay facilitate recovery of muscle from prolonged exercise by enhancingthe removal of nitrogen in the form of glutamine andalanine.

     

Effect of vitamin E deprivation and exercise training on induction of HSP70

Kelly, D. A., P. M. Tiidus, M. E. Houston, and E. G. Noble.Effect of vitamin E deprivation and exercise training on inductionof HSP70. J. Appl. Physiol. 81(6):2379-2385, 1996.To investigate the effects of dietary vitamin Edeprivation and chronic exercise on the relative content of selectedisoforms of the heat-shock protein 70 (HSP70) family in rat hindlimbmuscle, vitamin E was withheld for 16 wk from female rats thatunderwent treadmill run training during the final 8 wk. As indicated byincreased (P < 0.05) content of thestress-inducible isoform (HSP72), training did stress the exercisingmuscles. However, vitamin E deficiency did not alter HSP72 content innontrained rats and was associated with a lesser induction(P < 0.01) in some muscles oftrained animals. The constitutive isoform, which exhibited similarlevels in muscles of varying fiber types, was demonstrated to belargely refractory to exercise, with an equivocal response to vitamin Edeprivation. HSP72 content was correlated to type I myosin heavy chain(MHC-I) content but only in muscles of sedentary normal-diet rats.After training, HSP72 content in a muscle essentially devoid of MHC-I(superficial vastus lateralis) reached levels comparable to those in amuscle high in MHC-I (soleus).

     

Exercise training reduces skeletal muscle membrane arachidonate in the obese (fa/fa) Zucker rat

Compared with the lean(Fa/) genotype, obese(fa/fa) Zucker rats have arelative deficiency of muscle phospholipid arachidonate, and skeletalmuscle arachidonate in humans is positively correlated with insulinsensitivity. To assess the hypothesis that the positive effects ofexercise training on insulin sensitivity are mediated by increasedmuscle arachidonate, we randomized 20 lean and 20 obese weanling maleZucker rats to sedentary or treadmill exercise groups. After 9 wk,fasting serum, three skeletal muscles (white gastrocnemius, soleus, andextensor digitorum longus), and heart were obtained. Fasting insulinwas halved by exercise training in the obese rat. In whitegastrocnemius and extensor digitorum longus (fast-twitch muscles), butnot in soleus (a slow-twitch muscle) or heart, phospholipidarachidonate was lower in obese than in lean rats(P < 0.001). In all muscles,exercise in the obese rats reduced arachidonate(P < 0.03, by ANOVA contrast). Weconclude that improved insulin sensitivity with exercise in the obesegenotype is not mediated by increased muscle arachidonate and thatreduced muscle arachidonate in obese Zucker rats is unique tofast-twitch muscles.

     

Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure

Delp, Michael D., Changping Duan, John P. Mattson, andTimothy I. Musch. Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure.J. Appl. Physiol. 83(4):1291-1299, 1997.One of the primary consequences of leftventricular dysfunction (LVD) after myocardial infarction is adecrement in exercise capacity. Several factors have been hypothesizedto account for this decrement, including alterations in skeletal musclemetabolism and aerobic capacity. The purpose of this study was todetermine whether LVD-induced alterations in skeletal muscle enzymeactivities, fiber composition, and fiber size are1) generalized in muscles orspecific to muscles composed primarily of a given fiber type and2) related to the severity of theLVD. Female Wistar rats were divided into three groups: sham-operatedcontrols (n = 13) and rats withmoderate (n = 10) and severe(n = 7) LVD. LVD was surgicallyinduced by ligating the left main coronary artery and resulted inelevations (P < 0.05) in leftventricular end-diastolic pressure (sham, 5 ± 1 mmHg; moderate LVD,11 ± 1 mmHg; severe LVD, 25 ± 1 mmHg). Moderate LVDdecreased the activities of phosphofructokinase (PFK) and citratesynthase in one muscle composed of type IIB fibers but did not modifyfiber composition or size of any muscle studied. However, severe LVDdiminished the activity of enzymes involved in terminal and-oxidation in muscles composed primarily of type I fibers, type IIAfibers, and type IIB fibers. In addition, severe LVD induced areduction in the activity of PFK in type IIB muscle, a 10% reductionin the percentage of type IID/X fibers, and a corresponding increase inthe portion of type IIB fibers. Atrophy of type I fibers, type IIAfibers, and/or type IIB fibers occurred in soleus and plantarismuscles of rats with severe LVD. These data indicate that rats withsevere LVD after myocardial infarction exhibit1) decrements in mitochondrialenzyme activities independent of muscle fiber composition,2) a reduction in PFK activity in type IIB muscle, 3) transformationof type IID/X to type IIB fibers, and4) atrophy of type I, IIA, and IIBfibers.

     

Endurance training affects myosin heavy chain phenotype in regenerating fast-twitch muscle

Bigard, Xavier A., Chantal Janmot, Danièle Merino,Françoise Lienhard, Yannick C. Guezennec, and Anne D'Albis.Endurance training affects myosin heavy chain phenotype inregenerating fast-twitch muscle. J. Appl.Physiol. 81(6): 2658-2665, 1996.The aim of thisstudy was to analyze the effects of treadmill training (2 h/day, 5 days/wk, 30 m/min, 7% grade for 5 wk) on the expression of myosinheavy chain (MHC) isoforms during and after regeneration of afast-twitch white muscle [extensor digitorum longus (EDL)]. Male Wistar rats were randomly assigned to a sedentary(n = 10) or an endurance-trained (ET;n = 10) group. EDL muscle degeneration and regeneration were induced by two subcutaneous injections of a snaketoxin. Five days after induction of muscle injury, animals were trainedover a 5-wk period. It was verified that ~40 days after venomtreatment, central nuclei were present in the treated EDL muscles fromsedentary and ET rats. The changes in the expression of MHCs in EDLmuscles were detected by using a combination of biochemical andimmunocytochemical approaches. Compared with contralateral nondegenerated muscles, relative concentrations of types I, IIa, andIIx MHC isoforms in ET rats were greater in regenerated EDL muscles(146%, P < 0.05; 76%,P < 0.01; 87%,P < 0.01, respectively). Their elevation corresponded to a decreasein the relative concentration of type IIb MHC (36%,P < 0.01). Although type I accountedfor only 3.2% of total myosin in regenerated muscles from the ETgroup, the cytochemical analysis showed that the proportion of positive staining with the slow MHC antibody was markedly greater in regenerated muscles than in contralateral ones. Collectively, these results demonstrate that the regenerated EDL muscle is sensitive to endurance training and suggest that the training-induced shift in MHC isoforms observed in these muscles resulted from an additive effect of regeneration and repeated exercise.

     

Effects of adenosine on pressure-flow relationships in an in vitro model of compartment syndrome

Shrier, Ian, Ari Baratz, and Sheldon Magder. Effects ofadenosine on pressure-flow relationships in an in vitro model ofcompartment syndrome. J. Appl.Physiol. 82(3): 755-759, 1997.Blood flow throughskeletal muscle is best modeled with a vascular waterfall at thearteriolar level. Under these conditions, flow is determined by thedifference between perfusion pressure (Pper) and the waterfall pressure(Pcrit), divided by the arterial resistance (Ra). By pump perfusing anisolated canine gastrocnemius muscle(n = 6) after it was placed within anairtight box, with and without adenosine infusion, we observed aninteraction between the pressure surrounding a muscle (as occurs incompartment syndrome) and baseline vascular tone. Wetitrated adenosine concentration to double baseline flow. We measuredPcrit and Ra at box pressures (Pbox), which resulted in 100 (Pbox = 0),90, 75, and 50% flow without adenosine; and 200, 180, 150, 100, and50% flow with adenosine. Without adenosine, each 10% decline in flowwas associated with a 5.7 mmHg increase in Pcrit(P < 0.01). With adenosine, the samedecrease in flow was associated with a 2.6-mmHg increase in Pcrit(P < 0.01). Values of Pcrit at 50%of flow were almost identical. Each 10% decrease in flow was alsoassociated with 2.2% increase in Ra with or without adenosine(P < 0.001). Ra decreased withadenosine infusion (P < 0.05), andthere was no interaction between adenosine and flow (P > 0.9). We conclude thatincreases in pressure surrounding a muscle limit flow primarily throughchanges in Pcrit with and without adenosine-induced vasodilation. Theinteraction between Pbox and adenosine with respect to Pcrit but not Rasuggests that Pbox affects the tone of the vessels responsible forPcrit but not Ra.