Effects of 4wk of hindlimb suspension on skeletal muscle mitochondrial respiration in rats

Yajid, Fatima, Jacques G. Mercier, Béatrice M. Mercier, Hervé Dubouchaud, and Christian Préfaut.Effects of 4 wk of hindlimb suspension on skeletal musclemitochondrial respiration in rats. J. Appl.Physiol. 84(2): 479-485, 1998.We investigated inrats the effect of 4 wk of hypodynamia on the respiration of mitochondria isolated from four distinct muscles [soleus,extensor digitorum longus, tibial anterior, and gastrocnemius(Gas)] and from subsarcolemmal (SS) and intermyofibrillar (IMF)regions of mixed hindlimb muscles that mainly contained the four citedmuscles. With pyruvate plus malate as respiratory substrate, 4 wk ofhindlimb suspension produced an 18% decrease in state3 respiration for IMF mitochondria compared with thosein the control group (P < 0.05). TheSS mitochondria state 3 were notsignificantly changed. Concerning the four single muscles, themitochondrial respiration was significantly decreased in the Gasmuscle, which showed a 59% decrease in state3 with pyruvate + malate(P < 0.05). The other musclespresented no significant decrease in respiratory rate in comparisonwith the control group. With succinate + rotenone, there was nosignificant difference in the respiratory rate compared with therespective control group, whatever the mitochondrial origin (SS, orIMF, or from single muscle). We conclude that 4 wk of hindlimbsuspension alters the respiration of IMF mitochondria in hindlimbskeletal muscles and seems to act negatively on complex I of theelectron-transport chain or prior sites. The muscle mitochondria mostaffected are those isolated from the Gas muscle.

     

Induction of neuronal type nitric oxide synthase in skeletal muscle by chronic electrical stimulation in vivo

Reiser, Peter J., William O. Kline, and Pal L. Vaghy.Induction of neuronal type nitric oxide synthase in skeletal muscle by chronic electrical stimulation in vivo. J. Appl. Physiol. 82(4): 1250-1255, 1997.Fast-twitch skeletal muscles contain more neuronal-type nitricoxide synthase (nNOS) than slow-twitch muscles because nNOS is presentonly in fast (type II) muscle fibers. Chronic in vivo electricalstimulation of tibialis anterior and extensor digitorum longus musclesof rabbits was used as a method of inducing fast-to-slow fiber typetransformation. We have studied whether an increase in musclecontractile activity induced by electrical stimulation alters nNOSexpression, and if so, whether the nNOS expression decreases to thelevels present in slow muscles. Changes in the expression of myosinheavy chain isoforms and maximum velocity of shortening of skinnedfibers indicated characteristic fast-to-slow fiber type transformationafter 3 wk of stimulation. At the same time, activity of NOS doubled inthe stimulated muscles, and this correlated with an increase in theexpression of nNOS shown by immunoblot analysis. These data suggestthat nNOS expression in skeletal muscle is regulated by muscle activityand that this regulation does not necessarily follow the fast-twitchand slow-twitch pattern during the dynamic phase of phenotypetransformation.

     

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.

     

Mechanical properties of rabbit latissimus dorsi muscle after stretch and/or electrical stimulation

James, R. S., V. M. Cox, I. S. Young, J. D. Altringham, andD. F. Goldspink Mechanical properties of rabbit latissimus dorsimuscle after stretch and/or electrical stimulation.J. Appl. Physiol. 83(2): 398-406, 1997.The work loop technique was used to measure the mechanicalperformance in situ of the latissimus dorsi (LD) muscles of rabbitsmaintained under fentanyl anesthesia. After 3 wk of incrementallyapplied stretch the LD muscles were 36% heavier, but absolute poweroutput (195 mW/muscle) was not significantly changed relative to thatof external control muscle (206 mW). In contrast, continuous 10-Hzelectrical stimulation reduced power output per kilogram of muscle>75% after 3 or 6 wk and muscle mass by 32% after 6 wk. Whencombined, stretch and 10-Hz electrical stimulation preserved orincreased the mass of the treated muscles but failed to prevent an 80%loss in maximum muscle power. However, this combined treatmentincreased fatigue resistance to a greater degree than electricalstimulation alone. These stretched/stimulated muscles, therefore, aremore suitable for cardiomyoplasty. Nonetheless, further work will benecessary to find an ideal training program for this surgicalprocedure.

     

Oxidation of lactate and acetate in rat skeletal muscle: analysis by 13C-nuclear magnetic resonance spectroscopy

Bertocci, Loren A., John G. Jones, Craig R. Malloy, RonaldG. Victor, and Gail D. Thomas. Oxidation of lactateand acetate in rat skeletal muscle: analysis by¹³C-nuclear magnetic resonancespectroscopy. J. Appl. Physiol. 83(1): 32-39, 1997.The balance between carbohydrate and fatty acidutilization in skeletal muscle previously has been studied in vivo byusing a variety of methods such as arteriovenous concentrationdifferences and radioactive isotope tracer techniques. However, thesemethodologies provide only indirect estimates of substrate oxidation.We used ¹³C-nuclear magneticresonance (NMR) spectroscopy and non-steady-state isotopomer analysisto directly quantify the relative oxidation of two competing exogenoussubstrates in rat skeletal muscles. We infused[1,2-¹³C]acetate and[3-¹³C]lactateintravenously in anesthetized rats during the final 30 min of 35 (n = 10) or 95 (n = 10) min of intense, unilateral, rhythmic hindlimb contractions.¹³C-NMR spectroscopy andisotopomer analysis were performed on extracts of gastrocnemius andsoleus muscles from both the contracting and contralateralresting hindlimbs. We found that1)[¹³C]lactate and[¹³C]acetate were taken up and oxidized by both restingand contracting skeletal muscles; and2) high-intensity musclecontractions altered the pattern of substrate utilization such that therelative oxidation of acetate decreased while that of lactate remainedunchanged or increased. Based on these findings, we propose that¹³C-NMR spectroscopy incombination with isotopomer analysis can be used to study the generaldynamics of substrate competition between carbohydrates and fats in ratskeletal muscle.

     

Long-term facilitation of upper airway muscle activities in vagotomized and vagally intact cats

Mateika, J. H., and R. F. Fregosi. Long-termfacilitation of upper airway muscle activities in vagotomized andvagally intact cats. J. Appl. Physiol.82(2): 419-425, 1997.The primary purpose of the presentinvestigation was to determine whether long-term facilitation (LTF) ofupper airway muscle activities occurs in vagotomized and vagally intactcats. Tidal volume and diaphragm, genioglossus, and nasal dilatormuscle activities were recorded before, during, and after one carotidsinus nerve was stimulated five times with 2-min trains of constantcurrent. Sixty minutes after stimulation, nasal dilator andgenioglossus muscle activities were significantly greater than controlin the vagotomized cats but not in the vagally intact cats. Tidalvolume recorded from the vagotomized and vagally intact cats wassignificantly greater than control during the poststimulation period.In contrast, diaphragm activities were not significantly elevated inthe poststimulation period in either group of animals. We conclude that1) LTF of genioglossus and nasaldilator muscle activities can be evoked in vagotomized cats;2) vagal mechanisms inhibit LTF inupper airway muscles; and 3) LTF canbe evoked in accessory inspiratory muscles because LTF of inspiredtidal volume was greater than LTF of diaphragm activity.

     

Energetic driving forces are maintained in resting rat skeletal muscle after dietary creatine supplementation

The total creatine(TCr) pool of skeletal muscle is composed of creatine (Cr) andphosphocreatine (PCr). In resting skeletal muscle, the ratio ofPCr to TCr (PCr/TCr; PCr energy charge) is ~0.6-0.8, dependingon the fiber type. PCr/TCr is linked to the cellular free energy of ATPhydrolysis by the Cr kinase equilibrium. Dietary Cr supplementationincreases TCr in skeletal muscle. However, many previous studies havereported data indicating that PCr/TCr falls after supplementation,which would suggest that Cr supplementation alters the restingenergetic state of myocytes. This study investigated the effect of Crsupplementation on the energy phosphates of resting skeletal muscle.Male rats were fed either rodent chow (control) or chow supplementedwith 2% (wt/wt) Cr. After 2 wk on the diet, the gastrocnemius andsoleus muscles were freeze clamped and removed from anesthetizedanimals. Cr supplementation increased TCr, PCr, and Cr levels in thegastrocnemius by 20, 22, and 17%, respectively (P < 0.05). A numerical 6% higher mean soleus TCr in Cr-supplemented ratswas not statistically significant. All other energy phosphate concentrations, free energy of ATP hydrolysis, and PCr/TCr were notdifferent between the two groups in either muscle. We conclude that Crsupplementation simply increased TCr in fast-twitch rat skeletal musclebut did not otherwise alter resting cellular energetic state.

     

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.

     

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).

     

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.

     

Prior eccentric contractions impair maximal insulin action on muscle glucose uptake in the conscious rat

Asp, Sven, Allan Watkinson, Nicholas D. Oakes, and Edward W. Kraegen. Prior eccentric contractions impair maximal insulin action on muscle glucose uptake in the conscious rat.J. Appl. Physiol. 82(4):1327-1332, 1997.Our aim was to examine the effect of prioreccentric contractions on insulin action locally in muscle in theintact conscious rat. Anesthetized rats performed one-leg eccentriccontractions through the use of calf muscle electrical stimulationfollowed by stretch of the active muscles. Two days later, basal andeuglycemic clamp studies were conducted with the rats in the awakefasted state. Muscle glucose metabolism was estimated from2-[¹⁴C(U)]deoxy-D-glucoseandD-[3-³H]glucose administration, and comparisons were made between the eccentrically stimulated and nonstimulated (control) calfmuscles. At midphysiological insulin levels, effects ofprior eccentric exercise on muscle glucose uptake were notstatistically significant. Maximal insulin stimulation revealed reducedincremental glucose uptake above basal(P < 0.05 in the red gastrocnemius;P < 0.1 in the white gastrocnemiusand soleus) and impaired net glycogen synthesis in all eccentricallystimulated muscles (P < 0.05). Weconclude that prior eccentric contractions impair maximal insulin action (responsiveness) on local muscle glucose uptake and glycogen synthesis in the conscious rat.

     

Nitric oxide decreases lung injury after intestinal ischemia

Terada, Lance S., Nancy N. Mahr, and Eugene D. Jacobson.Nitric oxide decreases lung injury after intestinal ischemia. J. Appl. Physiol. 81(6):2456-2460, 1996.After injury to a primary organ, mediators arereleased into the circulation and may initiate inflammation of remoteorgans. We hypothesized that the local production of nitric oxide (NO)may act to limit the spread of inflammation to secondarily targetedorgans. In anesthetized rats, 30 min of intestinal ischemia followed by2 h of reperfusion (I/R) did not increase lung albumin leak. However,after treatment with N^G-nitro-L-arginine methyl ester(L-NAME), intestinal I/R led to increased lung leak, suggesting a protective effect of endogenous NO.The site of action of NO appeared to be the lung and not the gutbecause 1) after treatment withL-NAME, local delivery of NO tothe lung by inhalation abolished the increase in intestinal I/R-inducedlung leak; 2)L-NAME had no effect onepithelial permeability (⁵¹Cr-labeled EDTA clearance) ofreperfused small bowel; and 3) after treatment with L-NAME, localdelivery of NO to the gut by luminal perfusion did not improveepithelial permeability of reperfused intestines. Furthermore,L-NAME increased, and inhaled NOde- creased, the density of lung neutrophils in rats subjected to intestinal I/R, and treatment with the selectin antagonist fucoidan abolished L-NAME-induced lungleak in rats subjected to intestinal I/R. We conclude thatendogenous lung NO limits secondary lung injury after intestinal I/R bydecreasing pulmonary neutrophil retention.

     

Sprint training, in vitro and in vivo muscle function, and myosin heavy chain expression

Harridge, S. D. R., R. Bottinelli, M. Canepari, M. Pellegrino, C. Reggiani, M. Esbjörnsson, P. D. Balsom, and B. Saltin. Sprint training, in vitro and in vivo muscle function, and myosin heavy chain expression. J. Appl.Physiol. 84(2): 442-449, 1998.Sprint trainingrepresents the condition in which increases in muscle shortening speed,as well as in strength, might play a significant role in improvingpower generation. This study therefore aimed to determine the effectsof sprint training on 1) thecoupling between myosin heavy chain (MHC) isoform expression andfunction in single fibers, 2) thedistribution of MHC isoforms across a whole muscle, and3) in vivo muscle function. Sevenyoung male subjects completed 6 wk of training (3-s sprints) on a cycleergometer. Training was without effect on maximum shortening velocityin single fibers or in the relative distribution of MHC isoforms ineither the soleus or the vastus lateralis muscles. Electrically evokedand voluntary isometric torque generation increased(P < 0.05) after training in boththe plantar flexors (+8% at 50 Hz and +16% maximal voluntarycontraction) and knee extensors (+8% at 50 Hz and +7% maximalvoluntary contraction). With the shortening potential of the musclesapparently unchanged, the increased strength of the major lower limbmuscles is likely to have contributed to the 7% increase(P < 0.05) in peak pedal frequency during cycling.

     

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.

     

Effect of endurance exercise training on muscle glycogen supercompensation in rats

Nakatani, Akira, Dong-Ho Han, Polly A. Hansen, Lorraine A. Nolte, Helen H. Host, Robert C. Hickner, and John O. Holloszy. Effect of endurance exercise training on muscle glycogensupercompensation in rats. J. Appl.Physiol. 82(2): 711-715, 1997.The purpose of this study was to test the hypothesis that the rate and extent ofglycogen supercompensation in skeletal muscle are increased byendurance exercise training. Rats were trained by using a 5-wk-long swimming program in which the duration of swimming was gradually increased to 6 h/day over 3 wk and then maintained at 6 h/day for anadditional 2 wk. Glycogen repletion was measured in trained anduntrained rats after a glycogen-depleting bout of exercise. The ratswere given a rodent chow diet plus 5% sucrose in their drinking waterad libitum during the recovery period. There were remarkabledifferences in both the rates of glycogen accumulation and the glycogenconcentrations attained in the two groups. The concentration ofglycogen in epitrochlearis muscle averaged 13.1 ± 0.9 mg/g wet wtin the untrained group and 31.7 ± 2.7 mg/g in the trained group(P < 0.001) 24 h after the exercise.This difference could not be explained by a training effect on glycogensynthase. The training induced ~50% increases in muscle GLUT-4glucose transporter protein and in hexokinase activity inepitrochlearis muscles. We conclude that endurance exercise trainingresults in increases in both the rate and magnitude of muscle glycogensupercompensation in rats.

     

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.

     

Growth hormone/IGF-I and/or resistive exercise maintains myonuclear number in hindlimb unweighted muscles

Allen, David L., Jon K. Linderman, Roland R. Roy, Richard E. Grindeland, Venkat Mukku, and V. Reggie Edgerton. Growth hormone/IGF-I and/or resistive exercise maintains myonuclearnumber in hindlimb unweighted muscles. J. Appl.Physiol. 83(5): 1857-1861, 1997.In the presentstudy of rats, we examined the role, during 2 wk ofhindlimb suspension, of growth hormone/insulin-like growth factor I(GH/IGF-I) administration and/or brief bouts of resistance exercise in ameliorating the loss of myonuclei in fibers of the soleusmuscle that express type I myosin heavy chain. Hindlimb suspensionresulted in a significant decrease in mean soleus wet weight that wasattenuated either by exercise alone or by exercise plus GH/IGF-Itreatment but was not attenuated by hormonal treatment alone. Both meanmyonuclear number and mean fiber cross-sectional area (CSA) of fibersexpressing type I myosin heavy chain decreased after 2 wk of suspensioncompared with control (134 vs. 162 myonuclei/mm and 917 vs. 2,076 µm², respectively). NeitherGH/IGF-I treatment nor exercise alone affected myonuclear number orfiber CSA, but the combination of exercise and growth-factor treatmentattenuated the decrease in both variables. A significant correlationwas found between mean myonuclear number and mean CSA across allgroups. Thus GH/IGF-I administration and brief bouts of muscle loadinghad an interactive effect in attenuating the loss of myonuclei inducedby chronic unloading.

     

Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats

Marsh, Daniel R., David S. Criswell, James A. Carson, andFrank W. Booth. Myogenic regulatory factors during regeneration ofskeletal muscle in young, adult, and old rats. J. Appl. Physiol. 83(4): 1270-1275, 1997.Myogenicfactor mRNA expression was examined during muscle regeneration afterbupivacaine injection in Fischer 344/Brown Norway F1 rats aged 3, 18, and 31 mo of age (young, adult, and old, respectively). Mass of thetibialis anterior muscle in the young rats had recovered to controlvalues by 21 days postbupivacaine injection but in adult and old ratsremained 40% less than that of contralateral controls at 21 and 28 days of recovery. During muscle regeneration, myogenin mRNA wassignificantly increased in muscles of young, adult, and old rats 5 daysafter bupivacaine injection. Subsequently, myogenin mRNA levels inyoung rat muscle decreased to postinjection control values byday 21 but did not return to controlvalues in 28-day regenerating muscles of adult and old rats. Theexpression of MyoD mRNA was also increased in muscles atday 5 of regeneration in young, adult,and old rats, decreased to control levels by day14 in young and adult rats, and remained elevated inthe old rats for 28 days. In summary, either a diminished ability todownregulate myogenin and MyoD mRNAs in regenerating muscle occurs inold rat muscles, or the continuing myogenic effort includes elevatedexpression of these mRNAs.

     

Effect of leucine metabolite beta -hydroxy-beta -methylbutyrate on muscle metabolism during resistance-exercise training

Nissen, S., R. Sharp, M. Ray, J. A. Rathmacher, D. Rice, J. C. Fuller, Jr., A. S. Connelly, and N. Abumrad. Effect of leucinemetabolite -hydroxy--methylbutyrate on muscle metabolism duringresistance-exercise training. J. Appl.Physiol. 81(5): 2095-2104, 1996.The effects ofdietary supplementation with the leucine metabolite-hydroxy--methylbutyrate (HMB) were studied in two experiments.In study 1, subjects(n = 41) were randomized among threelevels of HMB supplementation (0, 1.5 or 3.0 g HMB/day) and two proteinlevels (normal, 117 g/day, or high, 175 g/day) and weight lifted for1.5 h 3 days/wk for 3 wk. In study 2,subjects (n = 28) were fed either 0 or3.0 g HMB/day and weight lifted for 2-3 h 6 days/wk for 7 wk. Instudy 1, HMB significantly decreased the exercise-induced rise in muscle proteolysis as measured by urine3-methylhistidine during the first 2 wk of exercise (linear decrease,P < 0.04). Plasma creatinephosphokinase was also decreased with HMB supplementation(week 3, linear decrease,P < 0.05). Weight lifted wasincreased by HMB supplementation when compared with the unsupplementedsubjects during each week of the study (linear increase,P < 0.02). In study2, fat-free mass was significantly increased inHMB-supplemented subjects compared with the unsupplemented group at 2 and 4-6 wk of the study (P < 0.05). In conclusion, supplementation with either 1.5 or 3 g HMB/daycan partly prevent exercise-induced proteolysis and/or muscledamage and result in larger gains in muscle function associated withresistance training.

     

Contractile function of single muscle fibers after hindlimb unweighting in aged rats

Thompson, L. V., and J. A. Shoeman. Contractilefunction of single muscle fibers after hindlimb unweighting in aged rats. J. Appl. Physiol. 84(1):229-235, 1998.This investigation determined how muscle atrophyproduced by hindlimb unweighting (HU) alters the contractile functionof single muscle fibers from older animals (30 mo). After 1 wk of HU,small bundles of fibers were isolated from the soleus muscles and thedeep region of the lateral head of the gastrocnemius muscles. Singleglycerinated fibers were suspended between a motor lever and forcetransducer, functional properties were studied, and the myosin heavychain (MHC) composition was determined electrophoretically. After HU, the diameter of type I MHC fibers of the soleus declined (88 ± 2 vs. 80 ± 4 µm) and reductions were observed in peak active force (47 ± 3 vs. 28 ± 3 mg) and peak specific tension(P_o; 80 ± 5 vs. 56 ± 5 kN/m²). The maximal unloadedshortening velocity increased. The type I MHC fibers from thegastrocnemius showed reductions in diameter (14%), peak active force(41%), and P_o (24%), whereas thetype IIa MHC fibers showed reductions in peak active force andP_o. Thus 1 wk ofinactivity has a significant effect on the force-generating capacity ofsingle skeletal muscle fibers from older animals in a fibertype-specific manner (type I MHC > type IIa MHC > type I-IIa MHC).The decline in the functional properties of single skeletal musclefibers in the older animals appears to be more pronounced than what hasbeen reported in younger animal populations.