Paretic muscle atrophy and non-contractile tissue content in individual muscles of the post-stroke lower extremity

Muscle atrophy is one of many factors contributing to post-stroke hemiparetic weakness. Since muscle force is a function of muscle size, the amount of muscle atrophy an individual muscle undergoes has implications for its overall force-generating capability post-stroke. In this study, post-stroke atrophy was determined bilaterally in fifteen leg muscles with volumes quantified using magnetic resonance imaging (MRI). All muscle volumes were adjusted to exclude non-contractile tissue content, and muscle atrophy was quantified by comparing the volumes between paretic and non-paretic sides. Non-contractile tissue or intramuscular fat was calculated by determining the amount of tissue excluded from the muscle volume measurement. With the exception of the gracilis, all individual paretic muscles examined had smaller volumes in the non-paretic side. The average decrease in volume for these paretic muscles was 23%. The gracilis volume, on the other hand, was approximately 11% larger on the paretic side. The amount of non-contractile tissue was higher in all paretic muscles except the gracilis, where no difference was observed between sides. To compensate for paretic plantar flexor weakness, one idea might be that use of the paretic gracilis actually causes the muscle to increase in size and not develop intramuscular fat. By eliminating non-contractile tissue from our volume calculations, we have presented volume data that more appropriately represents force-generating muscle tissue. Non-uniform muscle atrophy was observed across muscles and may provide important clues when assessing the effect of muscle atrophy on post-stroke gait.     

Effects of long-duration bed rest on structural compartments of m. soleus in man

Magnetic resonance imaging (MRI), histomorphometry and electron microscopy of muscle demonstrate that long-term exposure to actual or simulated weightlessness (including head down bed rest) leads to decreased volume of antigravity muscles in mammals. In muscles interbundle space is occupied by the connective tissue. Rat studies show that hindlimb unloading induces muscle fiber atrophy along with increase in muscle non-fiber connective tissue compartment. Beside that, usually 20% of the muscle fiber volume is comprised by non-contractile (non-myofibrillar) compartment. The aim of the present study was to compare changes in muscle volume, and in muscle fiber size with alterations in myofibrillar apparatus, and in connective tissue compartment in human m. soleus under conditions of 120 day long head down bed rest (HDBR).     

Magnetic Resonance Assessment of Hypertrophic and Pseudo-Hypertrophic Changes in Lower Leg Muscles of Boys with Duchenne Muscular Dystrophy and Their Relationship to Functional Measurements

Introduction

The primary objectives of this study were to evaluate contractile and non-contractile content of lower leg muscles of boys with Duchenne muscular dystrophy (DMD) and determine the relationships between non-contractile content and functional abilities.

Methods

Lower leg muscles of thirty-two boys with DMD and sixteen age matched unaffected controls were imaged. Non-contractile content, contractile cross sectional area and non-contractile cross sectional area of lower leg muscles (tibialis anterior, extensor digitorum longus, peroneal, medial gastrocnemius and soleus) were assessed by magnetic resonance imaging (MRI). Muscle strength, timed functional tests and the Brooke lower extremity score were also assessed.

Results

Non-contractile content of lower leg muscles (peroneal, medial gastrocnemius, and soleus) was significantly greater than control group (p<0.05). Non-contractile content of lower leg muscles correlated with Brooke score (r_s = 0.64-0.84) and 30 feet walk (r_s = 0.66-0.80). Dorsiflexor (DF) and plantarflexor (PF) specific torque was significantly different between the groups.

Discussion

Overall, non-contractile content of the lower leg muscles was greater in DMD than controls. Furthermore, there was an age dependent increase in contractile content in the medial gastrocnemius of boys with DMD. The findings of this study suggest that T₁ weighted MR images can be used to monitor disease progression and provide a quantitative estimate of contractile and non-contractile content of tissue in children with DMD.     

Skeletal muscle contractile and noncontractile components in young and older women and men.

To examine the influences of age, gender, and habitual physical activity level on human skeletal muscle composition, we developed a relatively simple magnetic resonance imaging method for the quantitation of leg anterior compartment contractile and noncontractile content. We studied 23 young (11 women and 12 men, 26-44 yr old) and 21 older (10 women and 11 men, 65-83 yr old) healthy adults. Analysis was by two-factor (age, gender) ANOVA. Physical activity, quantitated by three-dimensional accelerometer worn about the waist for 1 wk, was not different between groups. Men had larger contractile and noncontractile cross-sectional areas (cm(2)) than women, with no gender effect on percent noncontractile area. Young subjects had larger contractile areas and smaller absolute (cm(2)) and relative (percent total) noncontractile areas than older subjects. There was a significant linear relationship between physical activity and percent noncontractile area in older (r = -0.68, P = 0.002) but not young subjects. These data demonstrate a more than twofold increase in the noncontractile content of locomotor muscles in older adults and provide novel support for physical activity as a modulator of this age-related change in muscle composition.     

Volume of ankle dorsiflexors and plantar flexors determined with stereological techniques.

The validity of the methods used for determination of muscle mass has not been evaluated previously. We determined muscle mass by estimating muscle volume with assumption-free stereological techniques applied to magnetic resonance imaging (MRI) in 18 healthy untrained subjects (6 women, 12 men) aged 41 yr (29-64 yr; median, range). Muscle mass was also estimated by measuring leg circumference and cross-sectional muscle areas (CSA) from MRIs at three predetermined levels. Power [peak torque (PT)] of the ankle dorsiflexors and plantar flexors was estimated by using isokinetic dynamometry. Dorsiflexor volume (r2 = 0.76, P < 5 x 10(-6)) and CSA (r2 = 0.73, P < 5 x 10(-5)) were related to PT, whereas circumference was not (r2 = 0.17, not significant). Correspondingly, a relationship to plantar PT was established for plantar flexor volume (r2 = 0.69, P < 5 x 10(-5)) and CSA (r2 = 0.46, P < 5 x 10(-3)) but not leg circumference (r2 = 0.15, not significant). SDs of the residuals were smaller for the relationship between dorsiflexor PT and volume than between PT and CSA (0.42 vs. 0.45) for plantar flexors (1.5 vs. 2.0). By using the Cavalieri method, six MRI sections and 15 min of point counting are sufficient to obtain a valid estimate of the volume of the muscles of the lower leg.     

Muscle activities used by young and old adults when stepping to regain balance during a forward fall

The current study was undertaken to determine if age-related differences in muscle activities might relate to older adults being significantly less able than young adults to recover balance during a forward fall. Fourteen young and twelve older healthy males were released from forward leans of various magnitudes and asked to regain standing balance by taking a single forward step. Myoelectric signals were recorded from 12 lower extremity muscles and processed to compare the muscle activation patterns of young and older adults. Young adults successfully recovered from significantly larger leans than older adults using a single step (32.2° vs. 23.5°). Muscular latency times, the time between release and activity onset, ranged from 73 to 114 ms with no significant age-related differences in the shortest muscular latency times. The overall response muscular activation patterns were similar for young and older adults. However older adults were slower to deactivate three stance leg muscles and also demonstrated delays in activating the step leg hip flexors and knee extensors prior to and during the swing phase. In the forward fall paradigm studied, age-differences in balance recovery performance do not seem due to slowness in response onset but may relate to differences in muscle activation timing during the stepping movement.     

Differential catabolism of muscle protein in Garden Warblers (Sylvia borin): flight and leg muscle act as a protein source during long-distance migration

Samples of flight and leg muscle tissue were taken from migratory garden warblers at three different stages of migration: (1) pre-flight: when birds face an extended flight phase within the next few days, (2) post-flight: when they have just completed an extended flight phase, and (3) recovery: when they are at the end of a stop-over period following an extended flight phase. The changes in body mass are closely related to the changes in flight (P<0.001) and leg muscle mass (P<0.001), suggesting that the skeletal muscles are involved in the protein metabolism associated with migratory flight. From pre- to post-flight, the flight and the leg muscle masses decrease by about 22%, but are restored to about 12% above the pre-flight masses during the recovery period. Biochemical analyses show that following flight a selective reduction occurred in the myofibrillar (contractile) component of the flight muscle (P<0.01). As this selective reduction accounts only for a minor part of the muscle mass changes, sarcoplasmic (non-contractile) and myofibrillar proteins of both the flight and leg muscle act as a protein source during long-distance migration. As a loss of leg muscle mass is additionally observed besides the loss in flight muscle mass, mass change seems not to be strictly associated with the mechanical power output requirements during flight. Whereas the specific content of sarcoplasmic proteins in the flight muscle is nearly twice as high as that in the leg muscle (P<0.001), the specific content of myofibrillar proteins differs only slightly (P < 0.05), being comparably low in both muscles. The ratio of non-contractile to contractile proteins in the flight muscle is one of the highest observed in muscles of a vertebrate.     

Aging alters contractile properties and fiber morphology in pigeon skeletal muscle

In this study, we tested the hypothesis that skeletal muscle from pigeons would display age-related alterations in isometric force and contractile parameters as well as a shift of the single muscle fiber cross-sectional area (CSA) distribution toward smaller fiber sizes. Maximal force output, twitch contraction durations and the force–frequency relationship were determined in tensor propatagialis pars biceps muscle from young 3-year-old pigeons, middle-aged 18-year-old pigeons, and aged 30-year-old pigeons. The fiber CSA distribution was determined by planimetry from muscle sections stained with hematoxylin and eosin. Maximal force output of twitch and tetanic contractions was greatest in muscles from young pigeons, while the time to peak force of twitch contractions was longest in muscles from aged pigeons. There were no changes in the force–frequency relationship between the age groups. Interestingly, the fiber CSA distribution in aged muscles revealed a greater number of larger sized muscle fibers, which was verified visually in histological images. Middle-aged and aged muscles also displayed a greater amount of slow myosin containing muscle fibers. These data demonstrate that muscles from middle-aged and aged pigeons are susceptible to alterations in contractile properties that are consistent with aging, including lower force production and longer contraction durations. These functional changes were supported by the appearance of slow myosin containing muscle fibers in muscles from middle-aged and aged pigeons. Therefore, the pigeon may represent an appropriate animal model for the study of aging-related alterations in skeletal muscle function and structure.     

Contractile and elastic ankle joint muscular properties in young and older adults

The purpose of this study was to investigate age-related differences in contractile and elastic properties of both dorsi- (DF) and plantarflexor (PF) muscles controlling the ankle joint in young and older adults. Experimental data were collected while twelve young and twelve older male and female participants performed maximal effort isometric and isovelocity contractions on a dynamometer. Equations were fit to the data to give torque-angle (Tθ) and torque-angular velocity (Tω) relations. Muscle series-elasticity was measured during ramped dynamometer contractions using ultrasonography to measure aponeurosis extension as a function of torque; second order polynomials were used to characterize the torque-extension (TΔL) relation. The results showed no age differences in DF maximal torque and none for female PF; however, older males had smaller maximal PF torques compared to young males. In both muscle groups and genders, older adults had decreased concentric force capabilities. Both DF and PF TΔL relations were more nonlinear in the older adults. Older PF, but not DF muscles, were stiffer compared to young. A simple antagonism model suggested age-related differences in Tθ and Tω relations would be magnified if antagonistic torque contributions were included. This assessment of static, dynamic, and elastic joint properties affords a comprehensive view of age-related modifications in muscle function. Although many clinical studies use maximal isometric strength as a marker of functional ability, the results demonstrate that there are also significant age-related modifications in ankle muscle dynamic and elastic properties.     

Influence of complete spinal cord injury on skeletal muscle cross-sectional area within the first 6 months of injury

In this study we examined the influence of complete spinal cord injury (SCI) on affected skeletal muscle morphology within 6 months of SCI. Magnetic resonance (MR) images of the leg and thigh were taken as soon as patients were clinically stable, on average 6 weeks post injury, and 11 and 24 weeks after SCI to assess average muscle cross-sectional area (CSA). MR images were also taken from nine able-bodied controls at two time points separated from one another by 18 weeks. The controls showed no change in any variable over time. The patients showed differential atrophy (P = 0.0001) of the ankle plantar or dorsi flexor muscles. The average CSA of m. gastrocnemius and m. soleus decreased by 24% and 12%, respectively (P = 0.0001). The m. tibialis anterior CSA showed no change (P = 0.3644). As a result of this muscle-specific atrophy, the ratio of average CSA of m. gastrocnemius to m. soleus, m. gastrocnemius to m. tibialis anterior and m. soleus to m. tibialis anterior declined (P = 0.0001). The average CSA of m, quadriceps femoris, the hamstring muscle group and the adductor muscle group decreased by 16%, 14% and 16%, respectively (P< or =0.0045). No differential atrophy was observed among these thigh muscle groups, thus the ratio of their CSAs did not change (P = 0.6210). The average CSA of atrophied skeletal muscle in the patients was 45-80% of that of age- and weight-matched able-bodied controls 24 weeks after injury. In conclusion, the results of this study suggest that there is marked loss of contractile protein early after SCI which differs among affected skeletal muscles. While the mechanism(s) responsible for loss of muscle size are not clear, it is suggested that the development of muscular imbalance as well as diminution of muscle mass would compromise force potential early after SCI.     

Voluntary and electrically evoked strength characteristics of obese and nonobese preadolescent boys

Overweight and obese children demonstrate inferior motor performance for strength- and power-related activities requiring support or lifting of body weight. Our purpose here was to determine whether the inferior performance could be attributed to a lower strength to muscle area ratio in the obese. Eleven nonobese (16.6% fat) and 13 obese (35.5% fat) boys (9-13 years old) volunteered for the study. Peak torque was measured during voluntary isometric and isokinetic elbow flexion and knee extension at four joint angles and four velocities, respectively. The contractile properties, twitch torque, time to peak torque, and half-relaxation time were evoked for the elbow flexors by percutaneous stimulation. Elbow flexor and knee extensor cross-sectional areas (CSA) were determined by computed axial tomography taken at the mid-upper arm and mid-thigh, respectively. Isometric and isokinetic elbow flexion and knee extension strength normalized for body weight were significantly (p less than 0.05) higher in the nonobese compared to the obese boys. There were no significant (p greater than 0.05) differences, however, between groups for elbow flexor and knee extensor CSA or for absolute and relative (normalized for muscle CSA or the product of muscle CSA and height, the latter accounting for differences in moment arm length) isometric, isokinetic, or evoked twitch torque for elbow flexion or knee extension. Likewise, there were no differences between groups for the time-related contractile properties, time to peak torque, or half-relaxation time. These findings suggest that there is no difference in the intrinsic strength or contractile properties of the elbow flexor and knee extensor muscles between obese and nonobese pre-adolescent boys and that other factors, such as the handicapping effect of excess fat mass, probably account for the reduced motor performance of the obese child.     

Healthy older adults have insufficient hip range of motion and plantar flexor strength to walk like healthy young adults

Limited plantar flexor strength and hip extension range of motion (ROM) in older adults are believed to underlie common age-related differences in gait. However, no studies of age-related differences in gait have quantified the percentage of strength and ROM used during gait. We examined peak hip angles, hip torques and plantar flexor torques, and corresponding estimates of functional capacity utilized (FCU), which we define as the percentage of available strength or joint ROM used, in 10 young and 10 older healthy adults walking under self-selected and controlled (slow and fast) conditions. Older adults walked with about 30% smaller hip extension angle, 28% larger hip flexion angle, 34% more hip extensor torque in the slow condition, and 12% less plantar flexor torque in the fast condition than young adults. Older adults had higher FCU than young adults for hip flexion angle (47% vs. 34%) and hip extensor torque (48% vs. 27%). FCUs for plantar flexor torque (both age groups) and hip extension angle (older adults in all conditions; young adults in self-selected gait) were not significantly <100%, and were higher than for other measures examined. Older adults lacked sufficient hip extension ROM to walk with a hip extension angle as large as that of young adults. Similarly, in the fast gait condition older adults lacked the strength to match the plantar flexor torque produced by young adults. This supports the hypothesis that hip extension ROM and plantar flexor strength are limiting factors in gait and contribute to age-related differences in gait.     

Changes in size and compliance of the calf after 30 days of simulated microgravity

Increased leg venous compliance may contribute to postflight orthostatic intolerance in astronauts. We reported that leg compliance was inversely related to the size of the muscle compartment. The purpose of this study was to test the hypothesis that reduced muscle compartment after long-duration exposure to microgravity would cause increased leg compliance. Eight men, 31-45 yr old, were measured for vascular compliance of the calf and serial circumferences of the calf before and after 30 days of continuous 6 degrees head-down bed rest. Cross-sectional areas (CSA) of muscle, fat, and bone compartments in the calf were determined before and after bed rest by computed tomography. From before to after bed rest, calculated calf volume (cm3) decreased (P less than 0.05) from 1,682 +/- 83 to 1,516 +/- 76. Calf muscle compartment CSA (cm2) also decreased (P less than 0.05) from 74.2 +/- 3.6 to 70.6 +/- 3.4; calf compliance (ml.100 ml-1.mmHg-1.100) increased (P less than 0.05) from 3.9 +/- .7 to 4.9 +/- .5. The percent change in calf compliance after bed rest was significantly correlated with changes in calf muscle compartment CSA (r = 0.72, P less than 0.05). The increased leg compliance observed after exposure to simulated microgravity can be partially explained by reduced muscle compartment. Countermeasures designed to minimize muscle atrophy in the lower extremities may be effective in ameliorating increased venous compliance and orthostatic intolerance after spaceflight.     

Hypertrophic response to unilateral concentric isokinetic resistance training.

The purposes of this study were to 1) determine the effect of concentric isokinetic training on strength and cross-sectional area (CSA) of selected extensor and flexor muscles of the forearm and leg, 2) examine the potential for preferential hypertrophy of individual muscles within a muscle group, 3) identify the location (proximal, middle, or distal level) of hypertrophy within an individual muscle, and 4) determine the effect of unilateral concentric isokinetic training on strength and hypertrophy of the contralateral limbs. Thirteen untrained male college students [mean age 25.1 +/- 6.1 (SD) yr] volunteered to perform six sets of 10 repetitions of extension and flexion of the nondominant limbs three times per week for 8 wk, using a Cybex II isokinetic dynamometer. Pretraining and posttraining peak torque and muscle CSA measurements for both the dominant and nondominant limbs were determined utilizing a Cybex II isokinetic dynamometer and magnetic resonance imaging scanner, respectively. The results indicated significant (P less than 0.0008) hypertrophy in all trained muscle groups as well as preferential hypertrophy of individual muscles and at specific levels. None of the muscles of the contralateral limbs increased significantly in CSA. In addition, significant (P less than 0.0008) increases in peak torque occurred for trained forearm extension and flexion as well as trained leg flexion. There were no significant increases in peak torque, however, for trained leg extension or for any movement in the contralateral limbs. These data suggest that concentric isokinetic training results in significant strength and hypertrophic responses in the trained limbs.     

Muscle geometry affects accuracy of forearm volume determination by magnetic resonance imaging (MRI)

Upper extremity musculoskeletal modeling is becoming increasingly sophisticated, creating a growing need for subject-specific muscle size parameters. One method for determining subject-specific muscle volume is magnetic resonance imaging (MRI). The purpose of this study was to determine the validity of MRI-derived muscle volumes in the human forearm across a variety of muscle sizes and shapes. Seventeen cadaveric forearms were scanned using a fast-spoiled gradient echo pulse sequence with high isotropic spatial resolution (1mm(3) voxels) on a 3T MR system. Pronator teres (PT), extensor carpi radialis brevis (ECRB), extensor pollicis longus (EPL), flexor carpi ulnaris (FCU), and brachioradialis (BR) muscles were manually segmented allowing volume to be calculated. Forearms were then dissected, muscles isolated, and muscle masses obtained, which allowed computation of muscle volume. Intraclass correlation coefficients (ICC(2,1)) and absolute volume differences were used to compare measurement methods. There was excellent agreement between the anatomical and MRI-derived muscle volumes (ICC = 0.97, relative error = 12.8%) when all 43 muscles were considered together. When individual muscles were considered, there was excellent agreement between measurement methods for PT (ICC = 0.97, relative error = 8.4%), ECRB (ICC = 0.93, relative error = 7.7%), and FCU (ICC = 0.91, relative error = 9.8%), and fair agreement for EPL (ICC = 0.68, relative error = 21.6%) and BR (ICC = 0.93, relative error = 17.2%). Thus, while MRI-based measurements of muscle volume produce relatively small errors in some muscles, muscles with high surface area-to-volume ratios may predispose them to segmentation error, and, therefore, the accuracy of these measurements may be unacceptable.     

Comparison of identified leg motoneuron structure and function between larval and adult Manduca sexta

Persistent leg motoneurons of the moth Manduca sexta were investigated in larval and adult animals to compare their dendritic structures, intrinsic electrical properties and pattern of target innervation. The study focused on two identified motoneurons of the prothoracic leg. Despite the complete remodeling of leg muscles, the motoneurons innervated pretarsal flexor muscles in both larval and adult legs. Similarly, although the central dendrites regress and regrow, the branching pattern was similar with the exception of a prominent midline branch that was not present in the adult stage. The intrinsic electrical properties of the motoneurons differed between larval and adult stages. Larval motoneurons had significantly higher membrane input resistances and more depolarized resting membrane potentials than did motoneurons in pharate adults or adults. In all stages, one motoneuron had a low maximal firing frequency, whereas the second motoneuron, which innervated the other half of the muscle, had a high maximum firing frequency. Although the two motoneurons continued to innervate the same halves of the target muscle, their relative effects on muscular contraction were reversed during metamorphosis along with concomitant changes in intrinsic properties. Pretarsal flexor motoneurons in pharate adults (just prior to emergence) displayed properties similar to those in emerged adults. Accepted: 8 January 2000     

Architectural properties of distal forelimb muscles in horses,Equus caballus

Articular injuries in athletic horses are associated with large forces from ground impact and from muscular contraction. To accurately and noninvasively predict muscle and joint contact forces, a detailed model of musculoskeletal geometry and muscle architecture is required. Moreover, muscle architectural data can increase our understanding of the relationship between muscle structure and function in the equine distal forelimb. Muscle architectural data were collected from seven limbs obtained from five thoroughbred and thoroughbred-cross horses. Muscle belly rest length, tendon rest length, muscle volume, muscle fiber length, and pennation angle were measured for nine distal forelimb muscles. Physiological cross-sectional area (PCSA) was determined from muscle volume and muscle fiber length. The superficial and deep digital flexor muscles displayed markedly different muscle volumes (227 and 656 cm3, respectively), but their PCSAs were very similar due to a significant difference in muscle fiber length (i.e., the superficial digital flexor muscle had very short fibers, while those of the deep digital flexor muscle were relatively long). The ulnaris lateralis and flexor carpi ulnaris muscles had short fibers (17.4 and 18.3 mm, respectively). These actuators were strong (peak isometric force, Fmax=5,814 and 4,017 N, respectively) and stiff (tendon rest length to muscle fiber length, LT:LMF=5.3 and 2.1, respectively), and are probably well adapted to stabilizing the carpus during the stance phase of gait. In contrast, the flexor carpi radialis muscle displayed long fibers (89.7 mm), low peak isometric force (Fmax=555 N), and high stiffness (LT:LMF=1.6). Due to its long fibers and low Fmax, flexor carpi radialis appears to be better adapted to flexion and extension of the limb during the swing phase of gait than to stabilization of the carpus during stance. Including muscle architectural parameters in a musculoskeletal model of the equine distal forelimb may lead to more realistic estimates not only of the magnitudes of muscle forces, but also of the distribution of forces among the muscles crossing any given joint.     

The validity of ultrasound estimation of muscle volumes

The purpose of this study was to validate ultrasound muscle volume estimation in vivo. To examine validity, vastus lateralis ultrasound images were collected from cadavers before muscle dissection; after dissection, the volumes were determined by hydrostatic weighing. Seven thighs from cadaver specimens were scanned using a 7.5-MHz ultrasound probe (SSD-1000, Aloka, Japan). The perimeter of the vastus lateralis was identified in the ultrasound images and manually digitized. Volumes were then estimated using the Cavalieri principle, by measuring the image areas of sets of parallel two-dimensional slices through the muscles. The muscles were then dissected from the cadavers, and muscle volume was determined via hydrostatic weighing. There was no statistically significant difference between the ultrasound estimation of muscle volume and that estimated using hydrostatic weighing (p > 0.05). The mean percentage error between the two volume estimates was 0.4% +/- 6.9. Three operators all performed four digitizations of all images from one randomly selected muscle; there was no statistical difference between operators or trials and the intraclass correlation was high (>0.8). The results of this study indicate that ultrasound is an accurate method for estimating muscle volumes in vivo.     

Muscle protein metabolism responds similarly to exogenous amino acids in healthy younger and older adults during NO-induced hyperemia

The combination of increasing blood flow and amino acid (AA) availability provides an anabolic stimulus to the skeletal muscle of healthy young adults by optimizing both AA delivery and utilization. However, aging is associated with a blunted response to anabolic stimuli and may involve impairments in endothelial function. We investigated whether age-related differences exist in the muscle protein anabolic response to AAs between younger (30 ± 2 yr) and older (67 ± 2 yr) adults when macrovascular and microvascular leg blood flow were similarly increased with the nitric oxide (NO) donor, sodium nitroprusside (SNP). Regardless of age, SNP+AA induced similar increases above baseline (P ≤ 0.05) in macrovascular flow (4.3 vs. 4.4 ml·min(-1)·100 ml leg(-1) measured using indocyanine green dye dilution), microvascular flow (1.4 vs. 0.8 video intensity/s measured using contrast-enhanced ultrasound), phenylalanine net balance (59 vs. 68 nmol·min(-1)·100 ml·leg(-1)), fractional synthetic rate (0.02 vs. 0.02%/h), and model-derived muscle protein synthesis (62 vs. 49 nmol·min(-1)·100 ml·leg(-1)) in both younger vs. older individuals, respectively. Provision of AAs during NO-induced local skeletal muscle hyperemia stimulates skeletal muscle protein metabolism in older adults to a similar extent as in younger adults. Our results suggest that the aging vasculature is responsive to exogenous NO and that there is no age-related difference per se in AA-induced anabolism under such hyperemic conditions.