Changes In Oxidative Capacity Research Articles

Skeletal Muscle-Specific Ablation of raptor, but Not of rictor, Causes Metabolic Changes and Results in Muscle Dystrophy

Mammalian target of rapamycin (mTOR) is a central controller of cell growth. mTOR assembles into two distinct multiprotein complexes called mTOR complex 1 (mTORC1) and mTORC2. Here we show that the mTORC1 component raptor is critical for muscle function and prolonged survival. In contrast, muscles lacking the mTORC2 component rictor are indistinguishable from wild-type controls. Raptor-deficient muscles become progressively dystrophic, are impaired in their oxidative capacity, and contain increased glycogen stores, but they express structural components indicative of oxidative muscle fibers. Biochemical analysis indicates that these changes are probably due to loss of activation of direct downstream targets of mTORC1, downregulation of genes involved in mitochondrial biogenesis, including PGC1alpha, and hyperactivation of PKB/Akt. Finally, we show that activation of PKB/Akt does not require mTORC2. Together, these results demonstrate that muscle mTORC1 has an unexpected role in the regulation of the metabolic properties and that its function is essential for life.

Constitutive expression of inducible Hsp70 is linked to natural shifts in skeletal muscle phenotype.

Constitutive expression of heat shock protein 70 (Hsp70) is elevated in frequently recruited, metabolically efficient rodent striated muscle. We aimed to assess the relative importance of muscle phenotype vs. increased contractile activity on this pattern of expression using the rat diaphragm, which undergoes a dramatic and sustained increase in recruitment with parturition and development. Diaphragms were collected from rats of various ages (20 day fetus, 1 and 3 days, and 1, 3, 6 and 12 weeks postpartum; PP), and assessed for changes in oxidative capacity, Hsp70 and Type I myosin heavy chain (MHCI) (used as a marker of muscle phenotype changes). Oxidative capacity of the diaphragm (as indicated by citrate synthase activity) and whole body growth rate (% increase in body weight per week), factors thought to require chaperone activity, increased rapidly, peaked at 3-6 weeks PP and declined late in development. In contrast, at 1 week PP, increased contractile activity in the diaphragm had not altered the expression of Hsp70 protein or mRNA from fetal levels. Significant increases in Hsp70 were not observed until between 1 and 3 weeks, achieving their highest levels at 12 weeks PP. Both MHC I protein (r = 0.69, P = 0.001) and mRNA (r = 0.76, P = 0.001) were significantly correlated with their Hsp70 counterparts. Expression of Hsp70 in the developing diaphragm represents an adaptation associated with a shift towards a slower, more metabolically efficient adult phenotype rather than simply a response to contractile stress.

Chemistry‐climate interactions in the Goddard Institute for Space Studies general circulation model: 1. Tropospheric chemistry model description and evaluation

A tropospheric chemistry model has been developed within the Goddard Institute for Space Studies general circulation model (GCM) to study interactions between chemistry and climate change. The model uses simplified chemistry based on CO‐NOx‐HOx‐Ox‐CH4 and also includes a parameterization for isoprene emissions, the most important non‐methane hydrocarbon. The model reproduces observed annual cycles and mean distributions of key trace gases fairly well. It simulates preindustrial to present‐day changes similar to those seen in other simulations. For example, the global tropospheric ozone burden increases 45%, within the 25%–57% range of other studies. Annual average zonal mean surface ozone increases more than 125% at northern midlatitudes. Comparison between runs that allow calculated ozone to interact with the GCM and those that do not shows only minor ozone differences. The common usage of non‐interactive ozone seems adequate to simulate ozone distributions. However, use of coupled chemistry does alter the tropospheric oxidation capacity, enlarging the preindustrial to present‐day OH decrease by about 10% (−5.3% global annual average uncoupled, −5.9% coupled). Thus simulation of changes in oxidation capacity may be systematically biased (though a 10% difference is within the uncertainty). Global annual average radiative forcing from preindustrial to present‐day ozone change is 0.32 W m−2. The forcing seems to increase by ∼10% with coupled chemistry. Forcing greater than 0.8 W m−2 is seen over the United States, the Mediterranean area, central Asia, and the Arctic, with values greater than 1.5 W m−2 over parts of these areas during summer. Though there are local differences, the radiative forcing is overall in good agreement with other modeling studies in both magnitude and spatial distribution, demonstrating that the simplified chemistry is adequate for climate studies.

Selective Long‐Term Electrical Stimulation of Fast Glycolytic Fibres Increases Capillary Supply but not Oxidative Enzyme Activity in Rat Skeletal Muscles

Glycolytic fibres in rat extensor digitorum longus (EDL) and tibialis anterior (TA) were selectively activated, as demonstrated by glycogen depletion, by indirect electrical stimulation via electrodes implanted in the vicinity of the peroneal nerve using high frequency (40 Hz) trains (250 ms at 1 Hz) and low voltage (threshold of palpable contractions). This regime was applied 10 times per day, each bout being of 15 min duration with 60 min recovery, for 2 weeks. Cryostat sections of muscles were stained for alkaline phosphatase to depict capillaries, succinate dehydrogenase (SDH) to demonstrate oxidative fibres, and periodic acid-Schiff reagent (PAS) to verify glycogen depletion. Specific activity of hexokinase (HK), 6-phosphofructokinase, pyruvate kinase, glycogen phosphorylase and cytochrome c oxidase (COX) were estimated separately in homogenates of the EDL and the predominantly glycolytic cortex and oxidative core of the TA. Stimulation increased the activity of HK but not that of oxidative enzymes in fast muscles. Comparison of changes in oxidative capacity and capillary supply showed a dissociation in the predominantly glycolytic TA cortex. Here, COX was 3.9+/-0.68 microM min(-1) (g wet wt)-1 in stimulated muscles compared with 3.7+/-0.52 microM min(-1) (g wet wt)-1 in contralateral muscles (difference not significant), while the percentage of oxidative fibres (those positively stained for SDH) was also similar in stimulated (14.0+/-2.8 %) and contralateral (12.2 +/-1.9 %) muscles. In contrast, the capillary to fibre ratio was significantly increased (2.01+/-0.12 vs. 1.55+/-0.04, P<0.01). We conclude that capillary supply can be increased independently of oxidative capacity, possibly due to haemodynamic factors, and serves metabolite removal to a greater extent than substrate delivery.

Exercise training and peripheral vascular disease.

Conservative management is advocated as a treatment of choice for patients with intermittent claudication. This is a review of the mechanisms behind the improvement following an exercise rehabilitation programme. All Medline articles from the National Library of Medicine, USA containing the text words 'claudication' or 'peripheral vascular disease' and 'exercise' were reviewed. Cross-referencing from relevant articles was carried out. The poor physical status of a patient with intermittent claudication is not solely due to a reduction in blood flow to the lower limbs; associated factors, such as metabolic inefficiency, poor cardiorespiratory reserve and exercise-induced inflammation contribute. An exercise programme frequently improves both the physical aspect and quality of life, and the success of such exercise is multifactorial. An increase in the blood flow to the lower extremity is uncommon. Other factors, such as a redistribution of blood flow, changes in oxidative capacity of the skeletal muscles and greater utilization of oxygen, occur and the associated metabolic dysfunction of the skeletal muscles is rectified. Following exercise training, blood rheology improves and exercise-induced inflammation is ameliorated; cardiorespiratory status also benefits and the oxygen cost of exercise decreases.

Effects of genetic selection and voluntary activity on the medial gastrocnemius muscle in house mice.

In a previous study, we found that in house mice both genetic selection (10 generations of artificial selection for high voluntary activity on running wheels) and access to running wheels (7-8 weeks) elicited a modest increase in maximal oxygen consumption. Based on these results, we hypothesized that genetic selection would affect the changes in endurance and oxidative capacity of the medial gastrocnemius (MG) muscle induced by wheel access (training response). Wheel access increased the isotonic endurance of the MG in both genetically selected and random-bred (control) mice. However, this exercise-induced improvement in isotonic endurance of the MG was similar between genetically selected and control mice. Wheel access also increased the succinate dehydrogenase activity of MG muscle fibers in both selected and control lines. However, this exercise-induced increase in succinate dehydrogenase activity was comparable between genetically selected and control animals. Taken together, these results indicate that the modest increase in maximal oxygen consumption associated with genetic selection is not reflected by the training-induced changes in oxidative capacity and endurance of MG muscle fibers.

EFFECT OF WEIGHT REDUCTION, OBESITY PREDISPOSITION AND AEROBIC FITNESS ON SKELETAL MUSCLE MAXIMAL OXIDATIVE PHOSPHORYLATION BY 31P-MRS

1159 To test the hypothesis that low skeletal muscle oxidative capacity is involved in obesity pathogenesis, we used 31P-MRS to measure maximal oxidative phosphorylation in 11 obesity-prone women before and after diet-induced weight reduction, and in 10 matched, never-obese, controls and 7 endurance-trained controls. Oxidative phosphorylation was calculated following 90-s isometric plantar flexion at maximum effort from the phosphocreatine recovery time constant (TCPCr), the ADP recovery time constant (TCADP), and the change in PCr the first 14 s of recovery (OxPhos). Weight reduction of 10.9 ± 1.1 kg was not associated with a change in oxidative capacity. TCPCR was 44.5 ± 4.4 vs. 36.0 ± 2.4 s, TCADP was 25.0 ± 2.5 vs. 23.1 ± 1.7 s, and OxPhos was 0.25 ± 0.04 vs. 0.26 ± 0.03 mM/s (means ± SEM) before and after weight reduction, respectively. Oxidative phosphorylation was not different between post-obese and never-obese controls by TCPCR (36.0 ± 2.4 vs. 34.6 ± 2.5 s), TCADP (23.1 ± 1.7 vs. 20.1 ± 1.8 s), or OxPhos (0.26 ± 0.03 vs. 0.26 ± 0.03 mM ATP/s, post-obese vs. never-obese, respectively). However, TCPCr and TCADP were significantly faster (27.3 ± 3 and 14.8 ± 2.1 s, respectively), and OxPhos was significantly higher (0.37 ± 0.04 mM/s) in the endurance-trained compared to the post-obese group. These results suggest that oxidative phosphorylation is neither altered by diet-induced weight reduction nor reduced in normal-weight, post-obese women relative to never-obese controls. By contrast, oxidative phosphorylation is increased in endurance-trained women. Supported by NIH RO1 DK 49779-03 and RO1 DK 51684-01

Effects of Endurance Training on Mitochondrial Ultrastructure and Fiber Type Distribution in Skeletal Muscle of Patients With Stable Chronic Heart Failure

Objectives. The present study was designed to evaluate the effects of an ambulatory training program in patients with chronic heart failure (CHF) on the ultrastructural morphology of mitochondria and fiber type distribution of skeletal muscle and its relation to peripheral perfusion.Background. Recent studies in patients with CHF have suggested that intrinsic abnormalities in skeletal muscle can contribute to the development of early lactic acidosis and fatigue during exercise.Methods. Patients were prospectively randomized to either a training group (n = 9; mean [±SD] left ventricular ejection fraction [LVEF] 26 ± 10%) participating in an ambulatory training program or to a physically inactive control group (n = 9; LVEF 28 ± 10%). At baseline and after 6 months, patients underwent symptom-limited bicycle exercise testing with measurement of central and peripheral hemodynamic variables as well as percutaneous needle biopsies of the vastus lateralis muscle. The mitochondrial ultrastructure of skeletal muscle was analyzed by ultrastructural morphometry; cytochrome coxidase activity was visualized by histochemistry and subsequently quantitated by morphometry. The fiber type distribution was determined by adenosine triphosphatase staining.Results. After 6 months of exercise training there was a significant increase of 41% in the surface density of cytochrome coxidase–positive mitochondria (SVMOcox+) (p < 0.05 vs. control) and of 43% in the surface density of mitochondrial cristae (SVMC) (p < 0.05 vs. control). Furthermore, exercise training induced a 92% increase in the surface density of the mitochondrial inner border membrane (p < 0.05 vs. control). In contrast, the total number of cytochrome coxidase–positive mitochondria remained essentially unchanged. Exercise-induced improvement in peak oxygen uptake was closely linked to changes in SVMOcox+ (p < 0.01, r = 0.66). After exercise training, changes in submaximal femoral venous lactate levels were not related to changes in submaximal leg blood flow (r = −0.4), but were inversely related to changes in the volume density of mitochondria (p = 0.01; r = −0.6) as well as to changes in SVMC (p < 0.05; r = −0.5). After exercise training there was a “reshift” from type II to type I fibers (p < 0.05 vs. control).Conclusions. Patients with CHF who engage in regular physical exercise show enhanced oxidative enzyme activity in the working skeletal muscle and a concomitant reshift to type I fibers. These exercise-induced changes in oxidative capacity appear to be unrelated to changes in peripheral perfusion.(J Am Coll Cardiol 1997;29:1067–73)© 1997 by the American College of Cardiology

Changes in oxidative capacity and fatigue resistance in skeletal muscle

In conclusion, it appears that in general an increase in the fatigue resistance of a muscle is accompanied by an increase in its oxidative capacity. Fatigue resistance of a muscle seems to be partly determined by its oxidative capacity. On the single motor unit (Burke et al, 1973; Hamm et al, 1988; Kugelberg and Lindegren 1979; Larsson et al, 1991) and single fibre level (Nemeth et al, 1981) the relation between fatigue resistance and oxidative capacity seems to be valid. However, this does not appear necessarily to be the case on the level of the whole muscle. Kugelberg and Lindegren (1979) suggested, that the endurance of each link in the chain of events leading to contraction is under aerobic conditions matched to the contractile capacity of the fibre expressed by its oxidative enzyme activity. Therefore, it might be that several tests for endurance capacity are more strenuous than the aerobic capacity of the muscle. Indeed, several studies suggest that the Burke test (Burke et al, 1973) or other fatiguing protocols might primarily test for other endurance-related properties as the excitation-contraction coupling (Kernell et al, 1987; Mayne et al, 1991b). Another explanation for the discrepancy in changes in oxidative capacity and fatigue resistance might be, that the mechanical responses of the motor units (which have different biochemical and contractile properties) during the fatigue test do not summate linearly during whole muscle contraction as was found by Gardiner and Olha (1987).(ABSTRACT TRUNCATED AT 250 WORDS)

Diaphragmatic fiber type specific adaptation to endurance exercise

Recent evidence suggests that exercise training results in a significant improvement in the oxidative capacity of the mammalian diaphragm; however, limited data exist concernin g which diaphragmatic fiber types are metabolically altered due to training. To test the hypothesis that exercise training increases the oxidative capacity of diaphragmatic type I and IIa fibers only, we examinedthe effects of endurance training on the fiber type specific changes in oxidative capacity, cross-sectional area, and capillarity of the costal diaphragm. Female Fischer-344 rats (agc ca 180 days) were divided into either a sedentary control group ( n = 6) or an exercise training group ( n = 6). The trained animals exercised for 10 wks on a motor-driven treadmill (60 min·day −1; days·wk −1) at a work rate equal to ca 55–65%s% V̇ o 2max . Capillaries were identified histologically and fiber types determined using ATPase histochemistry. Fiber cross-sectional area (CSA) and succinate dehydrogenase (SDH) activity in individual fibers were measured using a computerized image analysis system. Compared to control animals, training did not increase the capillary to fiber ratio in any diaphragm fiber typc ( P > 0.05); however, training increased capillary density (capillary No. /CSA) in type lla fibers due to a reduction in cell CSA ifP > 0.05. Further, training resulted in significant ifp > 0.05 1 increases in total diaphragmatic SDH activity ( Δ increase = 17.5%) and an increase in SDH activity in both type I (Δ increase = 14%) and lla fibers ( Δ increase = 17.4%). In contrast, training did not alter ( P > 0.05) SDH activity in type llb fibers. These data support the hypothesis that endurance training results in significant improvements in the oxidative capacity of type I and lla fibers in the costal diaphragm of rodents. However, the increase in relative SDH activity and capillary density in type lla fibers is achieved primarily via a reduction in fiber CSA.

Adaptability of the oxidative capacity of motoneurons

Previous studies have demonstrated that a chronic change in neuronal activation can produce a change in soma oxidative capacity, suggesting that: (i) these 2 variables are directly related in neurons and (ii) ion pumping is an important energy requiring activity of a neuron. Most of these studies, however, have focused on reduced activation levels of sensory systems. In the present study the effect of a chronic increase or decrease in motoneuronal activity on motoneuron oxidative capacity and soma size was studied. In addition, the effect of chronic axotomy was studied as an indicator of whether cytoplasmic volume may also be related to the oxidative capacity of motoneurons. A quantitative histochemical assay for succinate dehydrogenase activity was used as a measure of motoneuron oxidative capacity in experimental models in which chronic electromyography has been used to verify neuronal activity levels. Spinal transection reduced, and spinal isolation virtually eliminated lumbar motoneuron electrical activity. Functional overload of the plantaris by removal of its major synergists was used to chronically increase neural activity of the plantaris motor pool. No change in oxidative capacity or soma size resulted from either a chronic increase or decrease in neuronal activity level. These data indicate that the chronic modulation of ionic transport and neurotransmitter turnover associated with action potentials do not induce compensatory metabolic responses in the metabolic capacity of the soma of lumbar motoneurons. Soma oxidative capacity was reduced in the axotomized motoneurons, suggesting that a combination of axoplasmic transport, intracellular biosynthesis and perhaps neurotransmitter turnover represent the major energy demands on a motoneuron. While soma oxidative capacity may be closely related to neural activity in some neural systems, e.g. visual and auditory, lumbar motoneurons appear to be much less sensitive to modulations in chronic activity levels.

Skeletal muscle oxidative capacity, antioxidant enzymes, and exercise training

The purposes of this study were to determine whether exercise training induces increases in skeletal muscle antioxidant enzymes and to further characterize the relationship between oxidative capacity and antioxidant enzyme levels in skeletal muscle. Male Sprague-Dawley rats were exercise trained (ET) on a treadmill 2 h/day at 32 m/min (8% incline) 5 days/wk or were cage confined (sedentary control, S) for 12 wk. In both S and ET rats, catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) activities were directly correlated with the percentages of oxidative fibers in the six skeletal muscle samples studied. Muscles of ET rats had increased oxidative capacity and increased GPX activity compared with the same muscles of S rats. However, SOD activities were not different between ET and S rats, but CAT activities were lower in skeletal muscles of ET rats than in S rats. Exposure to 60 min of ischemia and 60 min of reperfusion (I/R) resulted in decreased GPX and increased CAT activities but had little or no effect on SOD activities in muscles from both S and ET rats. The I/R-induced increase in CAT activity was greater in muscles of ET than in muscles of S rats. Xanthine oxidase (XO), xanthine dehydrogenase (XD), and XO + XD activities after I/R were not related to muscle oxidative capacity and were similar in muscles of ET and S rats. It is concluded that although antioxidant enzyme activities are related to skeletal muscle oxidative capacity, the effects of exercise training on antioxidant enzymes in skeletal muscle cannot be predicted by measured changes in oxidative capacity.

Influence of mitochondrial content on the sensitivity of respiratory control.

This study evaluated the sensitivity of mitochondrial respiratory control as a function of tissue oxidative capacity. The mitochondrial content of rat skeletal muscle was increased by exercise training or decreased by hypothyroidism. Muscles of the lower hindlimb were stimulated to tetanically contract in situ for 3 min at one of four frequencies to elicit a 30-fold range of oxygen consumption rates. Freeze-clamped sections of fast-twitch red gastrocnemius muscle were extracted and analyzed for metabolite levels. The sensitivity of respiratory control was examined for three models of cytosolic respiratory control (ADPf, ATP/ADPf, and ATP/(ADPf X Pi]; for each proposed model, sensitivity went up as mitochondrial content increased. Thus, a smaller change in cytosolic modulator (e.g., ADPf) is required as oxidative capacity increases. Increases in the sensitivity of cytosolic respiratory control resulted in lower flux through the near-equilibrium energy exchange reactions of creatine kinase and myokinase such that calculated free concentrations of ADP and AMP were less. Other energetically important reactions/pathways were also affected. Accumulation of lactate and the deamination of AMP to IMP were lower in tissues with higher mitochondrial content. In summary, changes in oxidative capacity directly influence the sensitivity of cytosolic respiratory control and this, in turn, has important consequences for maintenance of cellular energy balance.

Age-related changes in oxidative capacity of the gastrocnemius muscle in normal and dystrophic ( [formula omitted]) mice

The hind limb muscles of dy 2J dy 2J mice appear more oxidative than normal hind limb muscles when assayed histochemically. In some cases, biochemical assay of oxidative capacity does not match histochemical data, and in some dy 2J mice, particularly old animals, there appears to be a decline in biochemically assayed oxidative enzymes. The current study cyto-biochemically assayed succinic dehdrogenase activity of the gastrocnemius muscle in dy 2J and normal mice. The assays were conducted over a maturation time course of 1 to 6 months of age. Additionally, the gastrocnemius muscle was divided into two distinct regions, a superficial region, containing largely glycolytic fast-twitch fibers (SGM), and a deeper region of mixed, largely oxidative fibers (DGM) in normal animals. Assay of the whole muscle and the two regions of each individual muscle showed that the dy 2J muscle increased in SDH activity with maturation and was significantly greater than the change observed in normal muscle during the same period. The increase in the whole muscle SDH activity was accounted for increases noted in the SGM. The dy 2J DGM, which showed marked morphologic degeneration, had neither an increase nor a decrease in measured SDH activity. Michaelis-Menton analysis of the enzymatic assay indicated that the V max, and not the K m , of the dystrophic muscle enzyme system was higher than normal, suggesting a change in quantity of enzyme present, and not altered function of the system. The observed increases occurred for 4 months of maturation and then began a decline, which was noted at 6 months. Coupled with the time course of gastrocnemius muscle degeneration (the glycolytic region was slow—very little by 4 months; the mixed was fast—highly degenerated by 1 to 2 months), the results of this study suggest that oxidative capacity in the dy 2J gastrocnemius muscle increased with maturation until it became obscured by inherant muscle wasting in a particular dy 2J muscle region. By comparison, analysis of the large glycolytic triceps muscle, a forelimb muscle which does not receive pseudomyotonia, indicated that this muscle did not increase in SDH activity in dystrophic animals, which showed the abnormal increase in the activity of the hind limb gastrocnemius. Thus the relationship of pseudomyotonia to increasing oxidative activity in the hind limb muscles of dystrophic animals was evident.

Capillarity, oxidative capacity and fibre composition of the soleus and gastrocnemius muscles of rats in hypothyroidism.

Muscle capillarity, mean and maximal diffusion distances and muscle fibre composition were evaluated in frozen sections stained for myosin ATPase of the soleus and the white area of the gastrocnemius medial head (gastrocnemius) of rats made hypothyroid by the injection of propylthiouracil (PTU) (50 mg kg-1) every day for 21 or 42 days. Oxygen consumption in the presence of excess ADP and Pi with pyruvate plus malate as substrates and the activity of cytochrome c oxidase were measured in muscle homogenates. Treatment with PTU decreased body oxygen consumption and the concentration of triiodothyronine in plasma. The capacity of the soleus and gastrocnemius muscles' homogenates to oxidize pyruvate plus malate and their cytochrome c oxidase activity were reduced after 21 or 42 days of treatment with PTU. Fibre composition in the soleus muscle was changed by treatment with PTU. There was a decrease in the proportion of type IIa or fast glycolytic oxidative fibres and an increase in type I or slow oxidative fibres. After 21 days of PTU administration there was also an increase in the proportion of fibres classified as IIc. The changes in fibre composition are believed to be the result of changes in the types of myosin synthesized by the fibres. Therefore, the fibres classified as IIc are, most probably, IIa fibres in the process of changing their myosin to that of the type I fibres. No changes in fibre composition were evident in the white area of the gastrocnemius medial head, an area made up of IIb or fast glycolytic fibres. The indices of capillarity: capillary density and capillary to fibre ratio, as well as mean and maximal diffusion distances from the capillaries, were not changed by the treatment with PTU in the muscles studied. The lack of changes in capillarity in spite of significant changes in oxidative capacity indicates that in skeletal muscle capillarity is not necessarily related to the oxidative capacity of the fibres.

The effect of hyperthyroidism on capillarity and oxidative capacity in rat soleus and gastrocnemius muscles.

Muscle fibre composition and capillarity were evaluated in frozen sections stained for myosin ATPase of the soleus and the white area of the medial head of the gastrocnemius of rats made hyperthyroid by injections of triiodothyronine (300-400 micrograms/kg body weight, every other day) for 2, 3 and 4 weeks. O2 consumption of homogenates of these muscles in the presence of excess inorganic phosphate (Pi) and ADP with pyruvate and malate as substrates was also measured. Increased oxidative capacity was observed in the soleus homogenates of hyperthyroid animals after 2 weeks of treatment while no changes were observed in the oxidative capacity of the homogenates of the white area of the medial head of the gastrocnemius, even after 4 weeks of treatment. Hyperthyroid animals showed a greater capillarity than controls in both muscles. In the soleus this was evident after 2 weeks of treatment while in the white area of the medial head of the gastrocnemius, it was evident only after 4 weeks of treatment. Fibre composition was affected in the soleus after 4 weeks of treatment. In control animals two fibre types were present in the soleus: slow-twitch oxidative fibres (s.o. or type I fibres) with a high ATPase activity after acid pre-incubation and fast-twitch glycolytic oxidative fibres (f.o.g. or type IIa fibres) with a low ATPase activity after acid pre-incubation. In the soleus of the hyperthyroid animals, a third fibre type with intermediate ATPase activity after acid pre-incubation was also present. This most probably represents a change in the type of myosin being synthesized by some fibres. No changes in fibre composition were observed in the white area of medial head of the gastrocnemius which was made up of only fast-twitch glycolytic fibres (f.g. or type IIb fibres). The changes in oxidative capacity and capillarity in the soleus preceded and did not seem to be related to the changes in the type of myosin being synthesized. The increased capillarity found in the white area of the medial head of the gastrocnemius of the hyperthyroid animals, in the absence of an increase in the oxidative capacity, indicates that the latter is not the only factor that determines capillarity in skeletal muscle.