The effects of exercise training programs on plasma concentrations of proenkephalin Peptide F and catecholamines.

To determine if exercise training alters the pattern and magnitude of plasma concentrations of proenkephalin Peptide F and epinephrine, plasma proenkephalin [107-140] Peptide F(ir) and catecholamines were examined pre-training (T-1), and after 4- (T-2), 8- (T-3), and 12-weeks (T-4) of training. 26 healthy men were matched and randomly assigned to one of three groups: heavy resistance strength training (Strength, n=9), high intensity endurance training (Endurance, n=8), or both training modalities combined (Combined, n=9). Blood was collected using a syringe with a cannula inserted into a superficial arm vein with samples collected at rest, after each 7 min stage and 5 and 15 min into recovery. With training, all groups observed shifted plasma Peptide F responses to graded exercise, where significant increases were observed at lower exercise intensities. Increases in plasma epinephrine with exercise were observed in all groups. The Combined group saw increases at 25% at T-3 and for 50% at T-2, T-3, and T-4 which was higher than T-1. The Endurance group demonstrated increases for 50% at T-1, T-2, T-3 but not at T-4. The plasma epinephrine response to graded exercise was reduced in the Strength group. Increases in plasma norepinephrine above rest were observed starting at 50% . The Strength group demonstrated a significant reduction in norepinephrine observed at 100% at T-3 and T-4. Peptide F and catecholamines responses to graded exercise can be altered by different types of physical exercise training. Simultaneous high intensity training may produce adrenal medulla exhaustion when compared to single mode training.

The influence of age and exercise modality on growth hormone bioactivity in women.

OBJECTIVE: Prior research has indicated that the loss of skeletal muscle mass and bone mineral density observed with aging is related to the prominent age-related decline in the concentration of serum growth hormone (GH). However, there is limited data on the effects of aging on GH responses to acute bouts of heavy resistance exercise (HRE) and aerobic exercise (AE). DESIGN: The present investigation examined the effects of a HRE protocol and an AE protocol on immunoreactive GH (IGH) and bioactive GH (BGH) in active young and old women. RESULTS: Older women had a diminished serum IGH response to both the HRE and AE protocols compared to the younger women, however a similar response was not observed in serum BGH. Additionally, the HRE protocol elicited a greater BGH response than the AE protocol exclusively in the younger group. CONCLUSIONS: Regardless of exercise mode, aging induces an increase in growth hormone polymerization that specifically results in a loss of serum growth hormone immunoreactivity without a concurrent loss of serum growth hormone bioactivity. The greater BGH response to the HRE protocol found in the younger group can be attributed to an unknown serum factor of molecular weight between 30 and 55kD that either potentiated growth hormone bioactivity in response to HRE or inhibited growth hormone bioactivity in response to AE.

Responses of proenkephalin Peptide F to aerobic exercise stress in the plasma and white blood cell biocompartments.

Proenkephalin Peptide F [107-140] is an enkephalin-containing peptide found predominantly within the adrenal medulla, co-packaged with epinephrine within the chromaffin granules. In vivo studies indicate that Peptide F has classic opioid analgesia effects; in vitro studies suggest potential immune cell interactions. In this investigation we examined patterns of Peptide F concentrations in different bio-compartments of the blood at rest and following sub-maximal cycle exercise to determine if Peptide F interacts with the white blood cell (WBC) bio-compartment during aerobic exercise. Eight physically active men (n=8) performed sub-maximal (80-85% V˙O2peak) cycle ergometer exercise for 30 min. Plasma Peptide F and WBC Peptide F immunoreactivity were examined pre-exercise, mid-exercise and immediately post-, 5-min post-, 15-min post-, 30-min post- and 60-min post-exercise and at similar time-points during a control condition (30 min rest). Peptide F concentrations significantly (p<0.05) increased at 5 and 60 min post-exercise, compared to pre-exercise concentrations. No significant increases in Peptide F concentrations in the WBC fraction were observed during or after exercise. However, a significant decrease was observed at 30 min post-exercise. An ultradian pattern of Peptide F distribution was apparent during rest. Furthermore, concentrations of T cells, B cells, NK cells, and total WBCs demonstrated significant changes in response to aerobic exercise. Data indicated that Peptide F was bound in significant molar concentrations in the WBC fraction and that this biocompartment may be one of the tissue targets for binding interactions. These data indicate that Peptide F is involved with immune cell modulation in the white blood circulatory biocompartment of blood.

Does AMP-activated protein kinase negatively mediate aged fast-twitch skeletal muscle mass?

The activity of 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK), a negative regulator of cell size, is up-regulated with age in resting and overloaded fast-twitch skeletal muscle but not slow-twitch muscle. Here, we provide evidence to support the hypothesis that elevated AMPK activity plays a potentially important integrative role in the age-related atrophy and diminished capacity for growth specific to fast-twitch skeletal muscle.

AMPK activation attenuates S6K1, 4E-BP1, and eEF2 signaling responses to high-frequency electrically stimulated skeletal muscle contractions.

Regulation of protein translation through Akt and the downstream mammalian target of rapamycin (mTOR) pathway is an important component of the cellular response to hypertrophic stimuli. It has been proposed that 5'-AMP-activated protein kinase (AMPK) activation during muscle contraction may limit the hypertrophic response to resistance-type exercise by inhibiting translational signaling. However, experimental manipulation of AMPK activity during such a stimulus has not been attempted. Therefore, we investigated whether AMPK activation can attenuate the downstream signaling response of the Akt/mTOR pathway to electrically stimulated lengthening muscle contractions. Extensor digitorum longus muscles (n = 8/group) were subjected to a 22-min bout of lengthening contractions by high-frequency sciatic nerve electrical stimulation (STIM) in young adult (8 mo) Fischer 344 x Brown Norway male rats. Forty minutes before electrical stimulation, rats were subcutaneously injected with saline or 5-aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR; 1 mg/g body wt), an AMPK activator. Stimulated and contralateral resting muscles were removed at 0, 20, and 40 min post-STIM, and AMPK, acetyl CoA carboxylase (ACC), Akt, eukaryotic initiation factor 4E-binding protein (4E-BP1), 70-kDa ribosomal protein S6 kinase (S6K1), and eukaryotic elongation factor 2 (eEF2) phosphorylations were assessed by Western blot. AICAR treatment increased (P < or = 0.05) post-STIM AMPK (Thr172) and ACC phosphorylation (Ser79/221), inhibited post-STIM S6K1 (Thr389) and 4E-BP1 (gel shift) phosphorylation, and elevated post-STIM eEF2 phosphorylation (Thr56). These findings suggest that translational signaling downstream of Akt/mTOR can be inhibited after lengthening contractions when preceded by AMPK activation and that energetic stress may be antagonistic to the hypertrophic translational signaling response to loaded muscle contractions.

Basal, but not overload-induced, myonuclear addition is attenuated by NG-nitro-L-arginine methyl ester (L-NAME) administration.

The purpose of this study was to examine the effect of blocking nitric oxide synthase (NOS) activity via NG-nitro-L-arginine methyl ester (L-NAME) on myonuclear addition in skeletal muscle under basal and overloaded conditions. Female Sprague-Dawley rats (approx. 220 g) were placed into 1 of the following 4 groups (n = 7-9/group): 7-day skeletal muscle overload (O), sham operation (S), skeletal muscle overload with L-NAME treatment (OLN), and sham operation with L-NAME treatment (SLN). Plantaris muscles were overloaded via bilateral surgical ablation of the gastrocnemius muscles and L-NAME (0.75 mg/mL) was administered in the animals' daily drinking water starting 2 days prior to surgery and continued until sacrifice. Myonuclear addition was assessed as subsarcolemmal incorporation of nuclei labeled with 5-bromo-2'-deoxyuridine (approx. 25 mg.(kg body mass)-1.day-1) delivered via osmotic pump during the overload period. As expected, muscle wet mass, total protein content, fiber cross-sectional area, and myonuclear addition were significantly higher (p

Impaired overload-induced muscle growth is associated with diminished translational signalling in aged rat fast-twitch skeletal muscle.

Impaired overload-induced protein synthesis and growth in aged fast-twitch skeletal muscle may result from diminished responsiveness of signalling intermediates controlling protein translation. Yet, potential age-related signalling decrements have never been examined in direct parallel with impaired overload-induced muscle growth in any model. To this end, we used Western blotting to examine the contents and phosphorylation states of mammalian target of rapamycin (mTOR) and its downstream translational signalling intermediates, 70 kDa ribosomal protein S6 kinase (S6k), ribosomal protein S6 (rpS6), eukaryotic elongation factor 2 (eEF2), and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), in conjunction with impaired growth in 1 week overloaded fast-twitch plantaris muscles (via unilateral gastrocnemius ablation) of old (O; 30 months) versus young adult (YA; 8 months) male Fischer344 x Brown Norway rats. The significantly (P

Chronic alcohol intake, resistance training, and muscle androgen receptor content.

INTRODUCTION: Chronic alcohol intake and resistance training (RT) have opposite effects on muscle physiology. PURPOSE: This study examined the effect of chronic alcohol intake on androgen receptor (AR) content in skeletal muscle to determine whether this effect was influenced by RT. METHODS: A total of 48 male Sprague Dawley(R) rats (mass = 456 +/- 1 g; mean +/- SE) were divided into five groups: baseline (N = 8), sedentary + alcohol (Sed-Al) (N = 8), sedentary + normal diet (Sed-Nml) (N = 8), exercise + alcohol (Ex-Al) (N = 12), and exercise + normal diet (Ex-Nml) (N = 12). Exercise groups completed a 6 1/3-wk "squat" RT protocol; alcohol groups received an ethanol-rich (35% caloric content of alcohol) diet throughout the 6 1/3-wk period. Baseline animals were killed at the onset of the 6 1/3-wk training period. RESULTS: Western blot analysis showed no effect of alcohol or RT on the AR of the extensor digitorum longus. Alcohol significantly reduced AR content of the rectus femoris (P < 0.05) and prevented RT-induced increases in AR content of the soleus. CONCLUSION: Chronic alcohol intake appeared to reduce the AR content of the type IIB fiber-predominant rectus femoris, and this reduction was not affected by RT. In the type I-predominant soleus, chronic alcohol intake alone had no effect but seemed to prevent RT-induced increases in AR content.

Angiotensin-converting enzyme inhibition attenuates myonuclear addition in overloaded slow-twitch skeletal muscle.

Because optimal overload-induced skeletal muscle hypertrophy requires ANG II, we aimed to determine the effects of blocking ANG II production [via angiotensin-converting enzyme (ACE) inhibition] on potential mediators of hypertrophy in overloaded skeletal muscle, namely, myonuclear addition and fibroblast content. In a 2 x 2 design, adult (200-225 g) female Sprague-Dawley rats were placed into one of four groups (n = 8/group): 7-day skeletal muscle overload, sham operation, 7-day skeletal muscle overload with ACE inhibition, or sham operation with ACE inhibition. Functional overloads of the plantaris and soleus muscles were produced via bilateral surgical ablation of the synergistic gastrocnemius muscle, and ACE inhibition was accomplished by the addition of the ACE inhibitor enalapril maleate to the animals' daily drinking water (0.3 mg/ml). Myonuclear addition and extrasarcolemmal nuclear proliferation, as measured by in vivo 5-bromo-2'-deoxyuridine labeling, were significantly (P < or = 0.05) increased by overload in both the slow-twitch soleus and fast-twitch plantaris muscles. Furthermore, ACE inhibition attenuated these overload-induced increases in the soleus muscle but not in the plantaris muscle. However, the effect of ACE inhibition on soleus extrasarcolemmal nuclei was not likely due to differences in fibroblast content because overload elicited significant increases in vimentin-positive areas in soleus and plantaris muscles, and these areas were unaffected by ACE inhibition in either muscle. There was no effect of ACE inhibition on any measure in sham-operated muscles. Collectively, these data indicate that ANG II may mediate the satellite cell response to overload in slow-twitch soleus but not in fast-twitch plantaris muscles and that this effect may occur independently of changes in fibroblast content.

Diminished overload-induced hypertrophy in aged fast-twitch skeletal muscle is associated with AMPK hyperphosphorylation.

Skeletal muscle mass declines with age, as does the potential for overload-induced fast-twitch skeletal muscle hypertrophy. Because 5'-AMP-activated protein kinase (AMPK) activity is thought to inhibit skeletal muscle protein synthesis and may therefore modulate muscle mass and hypertrophy, the purpose of this investigation was to examine AMPK phosphorylation status (a marker of AMPK activity) and its potential association with the attenuated overload-induced hypertrophy observed in aged skeletal muscle. One-week overload of fast-twitch plantaris and slow-twitch soleus muscles was achieved in young adult (8 mo; n = 7) and old (30 mo; n = 7) Fischer344 x Brown Norway male rats via unilateral gastrocnemius ablation. Significant (P < or = 0.05) age-related atrophy (as measured by total protein content) was noted in plantaris and soleus control (sham-operated) muscles. In fast-twitch plantaris muscles, percent hypertrophy with overload was significantly attenuated with age, whereas AMPK phosphorylation status as determined by Western blotting [phospho-AMPK (Thr172)/total AMPK] was significantly elevated with age (regardless of loading status). There was also a main effect of loading on AMPK phosphorylation status in plantaris muscles (overload > control). Moreover, a strong and significant negative correlation (r = -0.82) was observed between AMPK phosphorylation status and percent hypertrophy in the overloaded plantaris muscles of all animals. In contrast to the plantaris, overload-induced hypertrophy of the slow-twitch soleus muscle was similar between ages, and AMPK phosphorylation in this muscle was also unaffected by age or overload. These data support the possibility that an age-related elevation in AMPK phosphorylation may partly contribute to the attenuated hypertrophic response observed with age in overloaded fast-twitch plantaris muscle.

Responses of plasma proenkephalin peptide F in rats following 14 days of spaceflight.

INTRODUCTION: . Proenkephalin peptide F [107-140] is related to the enhancement of immune function, while microgravity has been shown to cause immuno-suppression. We investigated the physiological response of proenkephalin peptide F to microgravity. METHODS: There were 12 Fischer 344 female rats, ovariectomized at 10.5 wk of age, used to determine plasma concentrations of peptide F in response to a 14-d flight aboard the Columbia Space Shuttle mission STS-62. There were 36 other such rats that served as ground-based controls to separate the effects of microgravity from those of thermal stress, flight stress, and crowded habitats. Control groups of 12 rats each were kept under the following conditions: 1) 22 degrees C vivarium, 2) 28 degrees C vivarium, and 3) variable (Var) to mimic flight. The flight and control groups were housed in animal enclosure modules 21 d prior to flight and for the duration of the study. The rats were sacrificed within 4-5 h after landing, at which time blood samples were obtained. RESULTS: Body weights were obtained prior to sacrifice; mean values were flight, 199 g; 22 degrees C, 193 g; 28 degrees C, 192 g; and Var, 194 g. The flight group produced a significantly greater (p < or = 0.05) level of plasma peptide F (0.056 pmol x ml(-1)) compared with the controls (0.016, 0.022, and 0.016 pmol x ml(-1) for 22 degrees C, 28 degrees C, and Var, respectively). Flight animals demonstrated higher corticosterone concentrations and reduced T and B cell splenocyte counts than controls. CONCLUSIONS: These data indicate that the increases in proenkephalin peptide F observed with exposure to microgravity may present an adrenal-medullary response to cope with the decreased immune function and increased stress experienced during spaceflight and landing.

Unlike myofibers, neuromuscular junctions remain stable during prolonged muscle unloading.

This study assessed the effect of muscle unloading on the neuromuscular system. Sixteen male Fischer 344 rats were randomly assigned to either a hindlimb suspension (unloaded) or control group (N=8/group) for 16 days. Following this intervention period, pre- and postsynaptic features of the neuromuscular junctions (NMJs) of soleus muscles were stained with cytofluorescent techniques, and myofibers were histochemically stained for ATPase activity. The data indicate that 16 days of muscle unloading resulted in significant (P<0.05) atrophy among myofibers (>50%) that was evident among all three major fiber types (I, IIA and IIX), but failed to significantly alter any aspect of NMJ morphology quantified. These results demonstrate an impressive degree of NMJ resilience despite dramatic remodeling of associated myofibers. This may be of benefit during post-unloading rehabilitative measures where effective neuromuscular communication is essential.

Physiological changes with periodized resistance training in women tennis players.

PURPOSE: To compare the physiological and performance adaptations between periodized and nonperiodized resistance training in women collegiate tennis athletes. METHODS: Thirty women (19 +/- 1 yr) were assigned to either a periodized resistance training group (P), nonperiodized training group (NV), or a control group (C). Assessments for body composition, anaerobic power, VO2(max), speed, agility, maximal strength, jump height, tennis-service velocity, and resting serum hormonal concentrations were performed before and after 4, 6, and 9 months of resistance training performed 2-3 d.wk (-1). RESULTS: Nine months of resistance training resulted in significant increases in fat-free mass; anaerobic power; grip strength; jump height; one-repetition maximum (1-RM) leg press, bench press, and shoulder press; serve, forehand, and backhand ball velocities; and resting serum insulin-like growth factor-1, testosterone, and cortisol concentrations. Percent body fat and VO2(max) decreased significantly in the P and NV groups after training. During the first 6 months, periodized resistance training elicited significantly greater increases in 1-RM leg press (9 +/- 2 vs 4.5 +/- 2%), bench press (22 +/- 5 vs 11 +/- 8%), and shoulder press (24 +/- 7 vs 18 +/- 6%) than the NV group. The absolute 1-RM leg press and shoulder press values in the P group were greater than the NV group after 9 months. Periodized resistance training also resulted in significantly greater improvements in jump height (50 +/- 9 vs 37 +/- 7%) and serve (29 +/- 5 vs 16 +/- 4%), forehand (22 +/- 3 vs 17 +/- 3%), and backhand ball velocities (36 +/- 4 vs 14 +/- 4%) as compared with nonperiodized training after 9 months. CONCLUSIONS: These data demonstrated that periodization of resistance training over 9 months was superior for enhancing strength and motor performance in collegiate women tennis players.

Statistical analysis of fiber area in human skeletal muscle.

Previous research has indicated that 50 fiber measurements per individual for type I and II fibers would be sufficient to characterize the fiber areas. This study replicated the work of McCall et al. (1998) using the three major fiber types (I, IIA, and IIB) and sampling larger populations of fibers. Random blocks of fibers were also examined to investigate how well they correlated with the overall mean average fiber area. Using random blocks of 50 fibers provided an accurate reflection of the type IIB fibers (r = 0.96-0.98) but not for the type I (r = 0.85-0.94) or IIA fibers (r = 0.80-0.91). Type I fibers were consistently reflected by a random block of 150 fibers (r = 0.95-0.98) while type IIA fibers required random blocks of 200 fibers (r = 0.94-0.98), which appeared to provide an accurate reflection of the cross-sectional area. These results indicate that for a needle biopsy different numbers of fibers are needed depending on the fiber type to accurately characterize the mean fiber population.

Detraining produces minimal changes in physical performance and hormonal variables in recreationally strength-trained men.

The object of this study was to examine changes in muscular strength, power, and resting hormonal concentrations during 6 weeks of detraining (DTR) in recreationally strength-trained men. Each subject was randomly assigned to either a DTR (n = 9) or resistance training (RT; n = 7) group after being matched for strength, body size, and training experience. Muscular strength and power testing, anthropometry, and blood sampling were performed before the experimental period (T1), after 3 weeks (T2), and after the 6-week experimental period (T3). One-repetition maximum (1RM) shoulder and bench press increased in RT at T3 (p

Waging war on physical inactivity: using modern molecular ammunition against an ancient enemy.

A hypothesis is presented based on a coalescence of anthropological estimations of Homo sapiens' phenotypes in the Late Paleolithic era 10,000 years ago, with Darwinian natural selection synergized with Neel's idea of the so-called thrifty gene. It is proposed that humans inherited genes that were evolved to support a physically active lifestyle. It is further postulated that physical inactivity in sedentary societies directly contributes to multiple chronic health disorders. Therefore, it is imperative to identify the underlying genetic and cellular/biochemical bases of why sedentary living produces chronic health conditions. This will allow society to improve its ability to effect beneficial lifestyle changes and hence improve the overall quality of living. To win the war against physical inactivity and the myriad of chronic health conditions produced because of physical inactivity, a multifactorial approach is needed, which includes successful preventive medicine, drug development, optimal target selection, and efficacious clinical therapy. All of these approaches require a thorough understanding of fundamental biology and how the dysregulated molecular circuitry caused by physical inactivity produces clinically overt disease. The purpose of this review is to summarize the vast armamentarium at our disposal in the form of the extensive scientific basis underlying how physical inactivity affects at least 20 of the most deadly chronic disorders. We hope that this information will provide readers with a starting point for developing additional strategies of their own in the ongoing war against inactivity-induced chronic health conditions.

Effect of alkalosis on plasma epinephrine responses to high intensity cycle exercise in humans.

The purpose of this study was to determine the effects of alkalosis on epinephrine concentrations in response to a 90 s maximal exercise test. A group of ten healthy men ingested either a bicarbonate (BS) supplement (0.3 g x kg(-1) of body mass of sodium bicarbonate) or placebo mixture (P) prior to performing a 90 s maximal cycle ergometer test. An indwelling Teflon cannula was placed in the antecubital vein and blood samples were drawn at three times at rest separated by 10 min, immediately following the protocol, and at 2.5, 5, and 10 min post exercise to determine plasma epinephrine concentrations. Sodium bicarbonate ingestion significantly ( P<0.05) induced alkalosis both at rest [mean (SD) pH=7.42 (0.02) BS, 7.38 (0.02) P] and after the exercise protocol [pH=7.16 (0.02) BS, 7.12 (0.02) P]. Plasma epinephrine concentrations were not significantly different immediately post exercise between the two conditions [4.2 (0.6) compared to 4.2 (0.7) pmol x ml(-1) in BS and P, respectively]. Work performed and power output attained were not significantly different between the two treatment conditions [mean power=258.7 (35.1) W BS, 260.3 (35.4) W P; peak power=534.7 (61.6) W BS, 535.7 (54.4) W P]. The primary finding of this investigation was that orally-induced alkalosis does not significantly affect plasma epinephrine concentrations or performance following 90 s of maximal cycle exercise in untrained men.