Maintenance of myonuclear domain size in rat soleus after overload and growth hormone/IGF-I treatment

The purpose ofthis study was to determine the effects of functional overload (FO)combined with growth hormone/insulin-like growth factor I (GH/IGF-I)administration on myonuclear number and domain size in rat soleusmuscle fibers. Adult female rats underwent bilateral ablation of theplantaris and gastrocnemius muscles and, after 7 days of recovery, wereinjected three times daily for 14 days with GH/IGF-I (1 mg/kg each; FO + GH/IGF-I group) or saline vehicle (FO group). Intact rats receivingsaline vehicle served as controls (Con group). Muscle wet weight was32% greater in the FO than in the Con group: 162 ± 8 vs. 123 ± 16 mg. Muscle weight in the FO + GH/IGF-I group (196 ± 14 mg) was59 and 21% larger than in the Con and FO groups, respectively. Meansoleus fiber cross-sectional area of the FO + GH/IGF-I group (2,826 ± 445 µm²) was increasedcompared with the Con (2,044 ± 108 µm²) and FO (2,267 ± 301 µm²) groups. The difference infiber size between the FO and Con groups was not significant. Meanmyonuclear number increased in FO (187 ± 15 myonuclei/mm) and FO + GH/IGF-I (217 ± 23 myonuclei/mm) rats compared with Con (155 ± 12 myonuclei/mm) rats, although the difference between FO and FO + GH/IGF-I animals was not significant. The mean cytoplasmic volume permyonucleus (myonuclear domain) was similar across groups. These resultsdemonstrate that the larger mean muscle weight and fibercross-sectional area occurred when FO was combined with GH/IGF-Iadministration and that myonuclear number increased concomitantly withfiber volume. Thus there appears to be some mechanism(s) that maintainsthe myonuclear domain when a fiber hypertrophies.

     

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.

     

Growth hormone, IGF-I, and exercise effects on non-weightbearing fast muscles of hypophysectomized rats

Grossman, Elena J., Richard E. Grindeland, Roland R. Roy,Robert J. Talmadge, Juliann Evans, and V. Reggie Edgerton. Growth hormone, IGF-I, and exercise effects on non-weight-bearing fast musclesof hypophysectomized rats. J. Appl.Physiol. 83(5): 1522-1530, 1997.The effects ofgrowth hormone (GH) or insulin-like growth factor I (IGF-I) with orwithout exercise (ladder climbing) in countering the effects ofunweighting on fast muscles of hypophysectomized rats during 10 days ofhindlimb suspension were determined. Compared with untreated suspendedrats, muscle weights were 16-29% larger in GH-treated and5-15% larger in IGF-I-treated suspended rats. Exercise alone hadno effect on muscle weights. Compared with ambulatory control, themedial gastrocnemius weight in suspended, exercised rats was largerafter GH treatment and maintained with IGF-I treatment. The combinationof GH or IGF-I plus exercise in suspended rats resulted in an increasein the size of each predominant fiber type, i.e., types I, I+IIa andIIa+IIx, in the medial gastrocnemius compared with untreated suspendedrats. Normal ambulation or exercise during suspension increased theproportion of fibers expressing embryonic myosin heavy chain inhypophysectomized rats. The phenotype of the medial gastrocnemius wasminimally affected by GH, IGF-I, and/or exercise. These resultsshow that there is an IGF-I, as well as a GH, and exercise interactiveeffect in maintaining medial gastrocnemius fiber size in suspendedhypophysectomized rats.

     

Anabolic influences of insulin-like growth factor I and/or growth hormone on the diaphragm of young rats

Lewis, Michael I., Thomas J. LoRusso, and Mario Fournier.Anabolic influences of insulin-like growth factor I and/or growth hormone on the diaphragm of young rats. J. Appl. Physiol. 82(6): 1972-1978, 1997.It iscontroversial whether insulin-like growth factor I (IGF-I), growthhormone (GH), or their combination might enhance body growthand/or tissue anabolism in the well-fed animal with an intactsomatotrophic axis. To assess this further, we studied four groups ofadolescent rats: 1) control (Ctr),2) GH,3) IGF-I, and4) GH/IGF-I. IGF-I was given via anosmotic minipump, whereas GH was injected subcutaneously for a period of 72 h. Diaphragm (Dia) contractile and fatigue properties were determined in vitro. Quantitative histochemical and morphometric analyses were performed on Dia fibers. Total serum IGF-I levels weresignificantly increased in the groups receiving growth factors. Although body weight increased to a greater extent in the animals receiving growth factors, a further synergistic effect was noted in theGH/IGF-I animals compared with either GH or IGF-I groups. Costal Diamass was greater in the groups receiving growth factors. The Dia ofGH/IGF-I animals was more fatigue resistant than the Dia in Ctr. Thecross-sectional area of types IIa and IIx fibers were increased to asimilar extent in all groups receiving growth factors compared withCtr. Succinate dehydrogenase activity of type IIa fibers wassignificantly greater in the GH/IGF-I animals compared with the othergroups. We conclude that the short-term provision of growth factors towell-nourished, normally growing adolescent rats can accelerate bodygrowth and promote selective hypertrophy of predominantly type II Diafibers.

     

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.

     

Human growth hormone response to repeated bouts of aerobic exercise

Kanaley, J. A., J. Y. Weltman, J. D. Veldhuis, A. D. Rogol,M. L. Hartman, and A. Weltman. Human growth hormone response torepeated bouts of aerobic exercise. J. Appl.Physiol. 83(5): 1756-1761, 1997.We examinedwhether repeated bouts of exercise could override growth hormone (GH)auto-negative feedback. Seven moderately trained men were studied onthree occasions: a control day (C), a sequential exercise day (SEB; at1000, 1130, and 1300), and a delayed exercise day (DEB; at 1000, 1400, and 1800). The duration of each exercise bout was 30 min at 70%maximal O₂ consumption (O_{2 max}) on a cycleergometer. Standard meals were provided at 0600 and 2200. GH wasmeasured every 5-10 min for 24 h (0800-0800). Daytime(0800-2200) integrated GH concentrations were ~150-160% greater during SEB and DEB than during C: 1,282 ± 345, 3,192 ± 669, and 3,389 ± 991 min · µg · l¹for C, SEB, and DEB, respectively [SEB > C(P < 0.06), DEB > C(P < 0.03)]. There were nodifferences in GH release during sleep (2300-0700). Deconvolutionanalysis revealed that the increase in 14-h integrated GH concentrationon DEB was accounted for by an increase in the mass of GH secreted perpulse (per liter of distribution volume,l_v): 7.0 ± 2.9 and 15.9 ± 2.6 µg/l_v for C and DEB,respectively (P < 0.01). Comparisonof 1.5-h integrated GH concentrations on the SEB and DEB days (30 minexercise + 60 min recovery) revealed that, with each subsequentexercise bout, GH release apparently increased progressively, with aslightly greater increase on the DEB day [SEB vs. DEB: 497 ± 162 vs. 407 ± 166 (bout 1), 566 ± 152 vs. 854 ± 184 (bout2), and 633 ± 149 vs. 1,030 ± 352 min · µg · l¹(bout 3),P < 0.05]. We conclude thatthe GH response to acute aerobic exercise is augmented with repeatedbouts of exercise.

     

Influence of complete spinal cord injury on skeletal muscle within 6mo of injury

This study examined the influence of spinal cord injury (SCI) onaffected skeletal muscle. The right vastus lateralis muscle wasbiopsied in 12 patients as soon as they were clinically stable (average6 wk after SCI), and 11 and 24 wk after injury. Samples were also takenfrom nine able-bodied controls at two time points 18 wk apart. Surfaceelectrical stimulation (ES) was applied to the left quadriceps femorismuscle to assess fatigue at these same time intervals. Biopsies wereanalyzed for fiber type percent and cross-sectional area (CSA), fibertype-specific succinic dehydrogenase (SDH) and -glycerophosphatedehydrogenase (GPDH) activities, and myosin heavy chainpercent. Controls showed no change in any variable overtime. Patients showed 27-56% atrophy(P = 0.000) of type I, IIa, andIIax+IIx fibers from 6 to 24 wk after injury, resulting in fiber CSAapproximately one-third that of controls. Their fiber type specific SDHand GPDH activities increased (P  0.001) from 32 to 90% over the 18 wk, thereby approaching or surpassing control values. The relative CSA of type I fibers and percentage of myosin heavy chain type I did not change. There wasapparent conversion among type II fiber subtypes; type IIa decreasedand type IIax+IIx increased (P  0.012). Force loss during ES did not change over time for either groupbut was greater (P = 0.000) for SCIpatients than for controls overall (27 vs. 9%). The results indicatethat vastus lateralis muscle shows marked fiber atrophy, no change inthe proportion of type I fibers, and a relative independence ofmetabolic enzyme levels from activation during the first 24 wk afterclinically complete SCI. Over this time, quadriceps femoris muscleshowed moderately greater force loss during ES in patients than incontrols. It is suggested that the predominant response of mixed humanskeletal muscle within 6 mo of SCI is loss of contractile protein.Therapeutic interventions could take advantage of this to increasemuscle mass.

     

Muscle fiber hypertrophy, hyperplasia, and capillary density in college men after resistance training

McCall, G. E., W. C. Byrnes, A. Dickinson, P. M. Pattany,and S. J. Fleck. Muscle fiber hypertrophy, hyperplasia, and capillary density in college men after resistance training.J. Appl. Physiol. 81(5):2004-2012, 1996.Twelve male subjects with recreationalresistance training backgrounds completed 12 wk of intensifiedresistance training (3 sessions/wk; 8 exercises/session; 3 sets/exercise; 10 repetitions maximum/set). All major muscle groupswere trained, with four exercises emphasizing the forearm flexors.After training, strength (1-repetition maximum preacher curl) increasedby 25% (P < 0.05). Magneticresonance imaging scans revealed an increase in the biceps brachiimuscle cross-sectional area (CSA) (from 11.8 ± 2.7 to 13.3 ± 2.6 cm²;n = 8;P < 0.05). Muscle biopsies of thebiceps brachii revealed increases(P < 0.05) in fiber areas for type I(from 4,196 ± 859 to 4,617 ± 1,116 µm²;n = 11) and II fibers (from 6,378 ± 1,552 to 7,474 ± 2,017 µm²;n = 11). Fiber number estimated fromthe above measurements did not change after training (293.2 ± 61.5 × 10³ pretraining; 297.5 ± 69.5 × 10³ posttraining;n = 8). However, the magnitude ofmuscle fiber hypertrophy may influence this response because thosesubjects with less relative muscle fiber hypertrophy, but similarincreases in muscle CSA, showed evidence of an increase in fibernumber. Capillaries per fiber increased significantly(P < 0.05) for both type I(from 4.9 ± 0.6 to 5.5 ± 0.7;n = 10) and II fibers (from 5.1 ± 0.8 to 6.2 ± 0.7; n = 10). Nochanges occurred in capillaries per fiber area or muscle area. Inconclusion, resistance training resulted in hypertrophy of the totalmuscle CSA and fiber areas with no change in estimated fiber number,whereas capillary changes were proportional to muscle fiber growth.

     

IGF-I and/or growth hormone preserve diaphragm fiber size with moderate malnutrition

Resistance to theanabolic effects of growth hormone (GH) occurs with severe caloricdeficit. This study examined whether moderate caloric deficit (50% ofdaily intake for 7 days) in the adolescent rat exceeds a criticalthreshold for GH action and whether a combination of GH andinsulin-like growth factor I (IGF-I) would have enhanced anaboliceffects on the diaphragm (Dia). Five groups of rats (4 wk old) werestudied: 1) control (Ctl),2) nutritionally deprived (ND),3) ND + GH,4) ND + IGF-I, and5) ND + GH + IGF-I. IGF-I was givenby continuous infusion (200 µg/day). GH was injected subcutaneously(250 µg every 12 h). Contractile and fatigue properties of the Diawere determined in vitro. Quantitative histochemical methods were usedto determine Dia fiber type proportions, cross-sectional areas, andsuccinate dehydrogenase activities. The body weight of Ctl ratsincreased 46% compared with 7% in ND animals, whereas that of ND ratsreceiving growth factors was intermediate. Serum IGF-I levels werereduced 54% in ND animals and maintained with the provision of growthfactors. Dia fatigue resistance was improved in ND animals receivinggrowth factors. There were no differences in Dia contractileproperties, fiber type proportions, or succinate dehydrogenaseactivities across groups. ND resulted in atrophy/growth arrest of allDia fibers (20-32%) compared with Ctl. Administration of IGF-Iand/or GH completely prevented atrophy/growth arrest of all Diafibers. No additive or synergistic effects were noted. We propose thatthese growth factors may provide useful short-term adjunctivenutritional support in circumstances in which the provision of optimalnutrition may be delayed or inadequate.

     

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.

     

Exercise-induced changes in circulating growth factors with cyclic variation in plasma estradiol in women

Hornum, Mette, Dan M. Cooper, Jo Anne Brasel, Alina Bueno,and Kathy E. Sietsema. Exercise-induced changes in circulating growth factors and cyclic variation in plasma estradiol in women. J. Appl. Physiol. 82(6):1946-1951, 1997.The effect of 10 min of high-intensity cyclingexercise on circulating growth hormone (GH), insulin-like growthfactors I and II (IGF-I and -II), and insulin-like growth factorbinding protein 3 (IGF BP-3) was studied in nine eumenorrheic women(age 19-48 yr) at two different phases of the menstrual cycle.Tests were performed on separate mornings corresponding to thefollicular phase and to the periovulatory phase of the menstrual cycle,during which plasma levels of endogenous estradiol(E₂) were relatively low (272 ± 59 pmol/l) and high (1,112 ± 407 pmol/l), respectively. GHincreased significantly in response to exercise under bothE₂ conditions. Plasma GH before exercise (2.73 ± 2.48 vs. 1.71 ± 2.09 µg/l) and total GH over 10 min of exercise and 1-h recovery (324 ± 199 vs. 197 ± 163 ng) were both significantly greater for periovulatory phase than for follicular phase studies. IGF-I, but not IGF-II, increased acutely after exercise. IGF BP-3, assayed by radioimmunoassay, was not significantly different at preexercise, end exercise, or at 30-min recovery time points and was not different between the two study days.When assayed by Western blot, however, there was a significant increasein IGF BP-3 30 min after exercise for the periovulatory study. Thesefindings indicate that the modulation of GH secretion associated withmenstrual cycle variations in circulatingE₂ affects GH measured afterexercise, at least in part, by an increase in baseline levels. Theacute increase in IGF-I induced by exercise appears to be independentof the GH response and is not affected by menstrual cycle timing.

     

Skeletal muscle chemoreflex and pHi in exercise ventilatory control

Oelberg, David A., Allison B. Evans, Mirko I. Hrovat, PaulP. Pappagianopoulos, Samuel Patz, and David M. Systrom. Skeletal muscle chemoreflex and pH_i inexercise ventilatory control. J. Appl.Physiol. 84(2): 676-682, 1998.To determinewhether skeletal muscle hydrogen ion mediates ventilatory drive inhumans during exercise, 12 healthy subjects performed three bouts ofisotonic submaximal quadriceps exercise on each of 2 days in a 1.5-Tmagnet for ³¹P-magnetic resonancespectroscopy(³¹P-MRS). Bilaterallower extremity positive pressure cuffs were inflated to 45 Torr duringexercise (BLPP_ex) or recovery(BLPP_rec) in a randomized orderto accentuate a muscle chemoreflex. Simultaneous measurements were madeof breath-by-breath expired gases and minute ventilation, arterializedvenous blood, and by ³¹P-MRS ofthe vastus medialis, acquired from the average of 12 radio-frequencypulses at a repetition time of 2.5 s. WithBLPP_ex, end-exercise minuteventilation was higher (53.3 ± 3.8 vs. 37.3 ± 2.2 l/min;P < 0.0001), arterializedPCO₂ lower (33 ± 1 vs. 36 ± 1 Torr; P = 0.0009), and quadricepsintracellular pH (pH_i) more acid (6.44 ± 0.07 vs. 6.62 ± 0.07; P = 0.004), compared withBLPP_rec. Bloodlactate was modestly increased withBLPP_ex but without a change inarterialized pH. For each subject, pH_i was linearly relatedto minute ventilation during exercise but not to arterialized pH. Thesedata suggest that skeletal muscle hydrogen ion contributes to theexercise ventilatory response.

     

Exercise training increases sarcolemmal GLUT-4 protein and mRNA content in diabetic heart

Osborn, Brett A., June T. Daar, Richard A. Laddaga, Fred D. Romano, and Dennis J. Paulson. Exercise training increases sarcolemmal GLUT-4 protein and mRNA content in diabetic heart. J. Appl. Physiol. 82(3): 828-834, 1997.This study determined whether dynamic exercise training ofdiabetic rats would increase the expression of the GLUT-4 glucosetransport protein in prepared cardiac sarcolemmal membranes. Fourgroups were compared: sedentary control, sedentary diabetic, trainedcontrol, and trained diabetic. Diabetes was induced by intravenousstreptozotocin (60 mg/kg). Trained control and diabetic rats were runon a treadmill for 60 min, 27 m/min, 10% grade, 6 days/wk for 10 wk.Sarcolemmal membranes were isolated by using differentialcentrifugation, and the activity of sarcolemmalK⁺-p-nitrophenylphosphatase( pNPPase; an indicator ofNa⁺-K⁺-adenosinetriphosphataseactivity) was quantified. Hearts from the sedentary diabetic groupexhibited a significant depression of sarcolemmal pNPPaseactivity. Exercise training did not significantly alterpNPPase activity. Sedentary diabetic rats exhibited an 84 and 58% decrease in GLUT-4 protein and mRNA, respectively, relative tocontrol rats. In the trained diabetic animals, sarcolemmal GLUT-4protein levels were only reduced by 50% relative to control values,whereas GLUT-4 mRNA were returned to control levels. The increase inmyocardial sarcolemmal GLUT-4 may be beneficial to the diabetic heartby enhancing myocardial glucose oxidation and cardiac performance

     

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).

     

Lower limb skeletal muscle function after 6wk of bed rest

Berg, H. E., L. Larsson, and P. A. Tesch. Lower limbskeletal muscle function after 6 wk of bed rest. J. Appl. Physiol. 82(1): 182-188, 1997.Force,electromyographic (EMG) activity, muscle mass, and fibercharacteristics were studied in seven healthy men before and after 6 wkof bed rest. Maximum voluntary isometric and concentric knee extensortorque decreased (P < 0.05)uniformly across angular velocities by 25-30% after bed rest.Maximum quadricep rectified EMG decreased by 19 ± 23%, whereassubmaximum (100-Nm isometric action) EMG increased by 44 ± 28%.Knee extensor muscle cross-sectional area (CSA), assessed by usingmagnetic resonance imaging, decreased by 14 ± 4%. Maximum torqueper knee extensor CSA decreased by 13 ± 9%. Vastus lateralis fiberCSA decreased 18 ± 14%. Neither type I, IIA, and IIB fiberpercentages nor their relative proportions of myosin heavy chain (MHC)isoforms were altered after bed rest. Because the decline in strengthcould not be entirely accounted for by decreased muscle CSA, it issuggested that the strength loss is also due to factors resulting indecreased neural input to muscle and/or reduced specifictension of muscle, as evidenced by a decreased torque/EMG ratio.Additionally, it is concluded that muscle unloading in humans does notinduce important changes in fiber type or MHC composition or in vivomuscle contractile properties.

     

Myosin heavy chain mRNA transform to faster isoforms in immobilized skeletal muscle: a quantitative PCR study

Jänkälä, Heidi, Veli-Pekka Harjola, NielsErik Petersen, and Matti Härkönen. Myosin heavy chainmRNA transform to faster isoforms in immobilized skeletal muscle: aquantitative PCR study. J. Appl.Physiol. 82(3): 977-982, 1997.A quantitative polymerase chain reaction (PCR) method was used to measure the quantities of type I, IIa, IIx, and IIb myosin heavy chain (MHC) mRNAin total RNA preparations of the soleus, gastrocnemius, and plantarismuscles of normal and hindlimb-immobilized rats. Type IIx and even typeIIb MHC mRNA were demonstrated at extremely low levels in normalsoleus, 2.1 ± 0.4 × 10⁵and 5.0 ± 0.2 × 10⁵molecules of mRNA per microgram total RNA, respectively. Immobilization for 1 wk significantly altered the gene expression of MHC isoforms. Insoleus, both type IIx and IIb MHC genes became significantly upregulated, 24-fold (P < 0.005) and 2.6-fold (P < 0.05),respectively. In gastrocnemius, the level of type IIa MHC mRNAdecreased by 51% (P < 0.01) and thelevel of type IIx MHC mRNA increased by 140%(P < 0.05). In plantaris, the levelof type IIa MHC mRNA decreased by 58%(P < 0.005). In conclusion,immobilization changed the MHC mRNA profile in three different types ofskeletal muscle toward faster isoforms. The quantitative results permitreliable evaluation of changes in mRNA levels.

     

Muscle metabolites and performance during high-intensity, intermittent exercise

Six men werestudied during four 30-s "all-out" exercise bouts on anair-braked cycle ergometer. The first three exercise bouts wereseparated by 4 min of passive recovery; after the third bout, subjectsrested for 4 min, exercised for 30 min at 30-35% peakO₂ consumption, and rested for afurther 60 min before completing the fourth exercise bout. Peak powerand total work were reduced (P < 0.05) during bout 3 [765 ± 60 (SE) W; 15.8 ± 1.0 kJ] compared withbout 1 (1,168 ± 55 W, 23.8 ± 1.2 kJ), but no difference in exercise performance was observed betweenbouts 1 and4 (1,094 ± 64 W, 23.2 ± 1.4 kJ). Before bout 3, muscle ATP,creatine phosphate (CP), glycogen, pH, and sarcoplasmic reticulum (SR)Ca²⁺ uptake were reduced, whilemuscle lactate and inosine 5'-monophosphate wereincreased. Muscle ATP and glycogen before bout4 remained lower than values beforebout 1 (P < 0.05), but there were no differences in muscle inosine 5'-monophosphate, lactate, pH, and SR Ca²⁺ uptake. Muscle CP levelsbefore bout 4 had increased aboveresting levels. Consistent with the decline in muscle ATP wereincreases in hypoxanthine and inosine before bouts3 and 4. The decline in exercise performance does not appear to be related to a reduction inmuscle glycogen. Instead, it may be caused by reduced CP availability, increased H⁺ concentration,impairment in SR function, or some other fatigue-inducing agent.

     

Acid-base regulation after maximal exercise testing in late gestation

Kemp, Justin G., Felicia A. Greer, and Larry A. Wolfe.Acid-base regulation after maximal exercise testing in late gestation. J. Appl. Physiol. 83(2):644-651, 1997.This study employed Stewart's physicochemicalapproach to quantify the effects of pregnancy and strenuous exercise onthe independent determinants of plasmaH⁺ concentration([H⁺]). Subjects werenine physically active pregnant women [mean gestational age = 33 ± 1 (SE) wk] and 14 age-matched nonpregnant controls. Venousblood samples and respiratory data were obtained at rest and during 15 min of recovery from a maximal cycle ergometer test that involved 20 W/min increases in work rate to exhaustion. Mean values for[H⁺],PCO₂, and total protein increased,whereas those for bicarbonate concentration([HCO₃]) and the strong ion difference ([SID]) decreased in the transition fromrest to maximal exercise within both groups. At rest and throughoutpostexercise recovery, the pregnant group exhibited significantly lowermean values for PCO₂,[HCO₃], and total protein,whereas [SID] was significantly lower at rest and early recovery from exercise.[H⁺] was also lower atall sampling times in the pregnant group, but this effect wassignificant only at rest. Our results support the hypothesis thatreduced PCO₂ and weak acidconcentration are important mechanisms to regulate plasma[H⁺] and to maintain aless acidic plasma environment at rest and after exercise in lategestation compared with the nonpregnant state. These effects areestablished in the resting state and appear to be maintained aftermaximal exertion.

     

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.

     

Failure of prostaglandins to modulate the time course of blood flow during dynamic forearm exercise in humans

Shoemaker, J. K., H. L. Naylor, Z. I. Pozeg, and R. L. Hughson. Failure of prostaglandins to modulate the time course ofblood flow during dynamic forearm exercise in humans.J. Appl. Physiol. 81(4):1516-1521, 1996.The time course and magnitude of increases inbrachial artery mean blood velocity (MBV; pulsed Doppler), diameter(D; echo Doppler), mean perfusionpressure (MPP; Finapres), shear rate ( = 8 ^· MBV/D), andforearm blood flow (FBF = MBV ^· r²)were assessed to investigate the effect that prostaglandins (PGs) haveon the hyperemic response on going from rest to rhythmic exercise inhumans. While supine, eight healthy men performed 5 min of dynamichandgrip exercise by alternately raising and lowering a 4.4-kg weight(~10% maximal voluntary contraction) with a work-to-rest cycle of1:1 (s/s). When the exercise was performed with the arm positionedbelow the heart, the rate of increase in MBV and wasfaster compared with the same exercise performed above the heart.Ibuprofen (Ibu; 1,200 mg/day, to reduce PG-induced vasodilation) andplacebo were administered orally for 2 days before two separate testingsessions in a double-blind manner. Resting heart rate was reduced inIbu (52 ± 3 beats/min) compared with placebo (57 ± 3 beats/min)(P < 0.05) without change to MPP.With placebo, D increased in both armpositions from ~4.3 mm at rest to ~4.5 mm at 5 min of exercise(P < 0.05). This response was notaltered with Ibu (P > 0.05). Ibudid not alter the time course of MBV or forearm blood flow(P > 0.05) in either arm position. The was significantly greater in Ibu vs. placebo at 30 and 40 s of above the heart exercise and for all time points after 25 sof below the heart exercise (P < 0.05). Because PG inhibition altered the time course of at the brachial artery, but not FBF, it was concludedthat PGs are not essential in regulating the blood flow responses todynamic exercise in humans.