Effects of an external pneumatic compression device vs static compression garment on peripheral circulation and markers of sports performance and recovery.

PURPOSE: To identify the effects of a single 30 min partial lower leg external pneumatic compression (EPC) treatment compared to a static compression (SC) garment or a no treatment control (CTL) on markers of recovery and performance following a muscle damaging protocol. METHODS: Thirty healthy, active males (23 ± 3 years; 180.2 ± 9.0 cm; 81.6 ± 11.3 kg) performed 100 drop jumps from a 0.6 m box followed by a randomized, single 30 min treatment of either a partial lower leg EPC device worn below the knee and above the ankle (110 mmHg), SC garment (20-30 mmHg) covering the foot and calf just below the knee, or no treatment CTL, and then returned 24 and 48 h later. Participants were assessed for measures of muscle soreness, fatigue, hemodynamics, blood lactate, muscle thickness, circumferences, and performance assessments. RESULTS: The drop jump protocol significantly increased muscle soreness (p < 0.001), fatigue (p < 0.001), blood flow (p < 0.001), hemoglobin (p < 0.001), and muscle oxygen saturation (SMO2; p < 0.001). Countermovement jump and squat jump testing completed after treatment with either EPC, SC, or CTL revealed no differences for jump height between any condition. However, EPC treatment maintained consistent braking force and propulsive power measures across all timepoints for countermovement jump testing. EPC and SC treatment also led to better maintenance of squat jump performance for average relative propulsive force and power variables at 24 and 48 h compared to CTL. CONCLUSIONS: A single 30 min partial leg EPC treatment may lead to more consistent jump performance following a damaging bout of exercise.

Ischemic preconditioning has no effect on maximal arm cycling exercise in women.

PURPOSE: We investigated the effect of ischemic preconditioning (IPC) on performance of a 3 min maximal effort arm ergometer test in young women. METHODS: Twenty healthy women (23.1 (SD 3.3) years) performed a 3 min maximal effort arm cycling exercise, preceded by IPC on both arms or SHAM in a counterbalanced randomized crossover design. Both blood flow (via high resolution ultrasound; n = 17) and muscle oxygenation/deoxygenation (via near infrared spectroscopy; n = 5) were measured throughout the IPC/SHAM. Performance and perceptual/physiological (i.e., heart rate, blood lactate, rating of perceived exertion, and triceps brachialis oxygenation) parameters were recorded during the exercise test. RESULTS: Occlusion during IPC completely blocked brachial artery blood flow, decreased oxygenated hemoglobin/myoglobin (Δ[oxy(Hb + Mb)]), and increased deoxygenated Hb/Mb (Δ[deoxy(Hb + Mb)]). There were no differences (P > 0.797) in performance (peak, mean, and end power output) or in any perceptual/physiological variables during the 3 min all-out test between IPC/SHAM. During exercise, Δ[oxy(Hb + Mb)] initially decreased with no differences (P ≥ 0.296) between conditions and returned towards baseline by the completion of the test while Δ[deoxy(Hb + Mb)] increased with no differences between conditions and remained elevated until completion of the test (P ≥ 0.755). CONCLUSIONS: We verified the successful application of IPC via blood flow and NIRS measures but found no effects on performance of a 3 min maximal effort arm cranking test in young women.

Acute and chronic resistance training downregulates select LINE-1 retrotransposon activity markers in human skeletal muscle.

Herein, we examined if acute or chronic resistance exercise affected markers of skeletal muscle long interspersed nuclear element-1 (LINE-1) retrotransposon activity. In study 1, 10 resistance-trained college-aged men performed three consecutive daily back squat sessions, and vastus lateralis biopsies were taken before (Pre), 2 h following session 1 (Post1), and 3 days following session 3 (Post2). In study 2, 13 untrained college-aged men performed a full-body resistance training program (3 days/wk), and vastus lateralis biopsies were taken before ( week 0) and ~72 h following training cessation ( week 12). In study 1, LINE-1 mRNA decreased 42-48% at Post1 and 2 ( P < 0.05), and reverse transcriptase (RT) activity trended downward at Post2 (-37%, P = 0.067). In study 2, LINE-1 mRNA trended downward at week 12 (-17%, P = 0.056) while LINE-1 promoter methylation increased (+142%, P = 0.041). Open reading frame (ORF)2p protein expression (-24%, P = 0.059) and RT activity (-26%, P = 0.063) also trended downward by week 12. Additionally, changes in RT activity versus satellite cell number were inversely associated ( r = -0.725, P = 0.008). Follow-up in vitro experiments demonstrated that 48-h treatments with lower doses (1 µM and 10 µM) of efavirenz and nevirapine (non-nucleoside RT inhibitors) increased myoblast proliferation ( P < 0.05). However, we observed a paradoxical decrease in myoblast proliferation with higher doses (50 µM) of efavirenz and delavirdine. This is the first report suggesting that resistance exercise downregulates markers of skeletal muscle LINE-1 activity. Given our discordant in vitro findings, future research is needed to thoroughly assess whether LINE-1-mediated RT activity enhances or blunts myoblast, or primary satellite cell, proliferative capacity.

Skeletal muscle amino acid transporter and BCAT2 expression prior to and following interval running or resistance exercise in mode-specific trained males.

Endurance (END)- and resistance (RES)-trained males performed interval running or resistance exercise during three consecutive days (bouts 1-3). Muscle biopsies were obtained at baseline, 2 h post-bout 1, and 72 h post-bout 3. Amino acid transporter SNAT2 mRNA was 75% greater in END (group p = 0.008), and increased ~ 70% 2 h post in both groups (time p = 0.023). Amino acid transporter PAT1 mRNA was 2.7-fold greater in RES (group p = 0.002). Baseline protein levels of the mitochondrial aminotransferase BCAT2 were 79% greater in END (p = 0.015).

Correction to: Ten weeks of branched-chain amino acid supplementation improves select performance and immunological variables in trained cyclists.

For the author R. Mac Thompson, the first name should be R. Mac and the last name should be Thompson. On SpringerLink the name is listed correctly, but on PubMed he is listed as Mac Thompson R.

Effect of 1-week betalain-rich beetroot concentrate supplementation on cycling performance and select physiological parameters.

PURPOSE: Betalains are indole-derived pigments found in beet root, and recent studies suggest that they may exert ergogenic effects. Herein, we examined if supplementation for 7 days with betalain-rich beetroot concentrate (BLN) improved cycling performance or altered hemodynamic and serum analytes prior to, during and following a cycling time trial (TT). METHODS: Twenty-eight trained male cyclists (29 ± 10 years, 77.3 ± 13.3 kg, and 3.03 ± 0.62 W/kg) performed a counterbalanced crossover study whereby BLN (100 mg/day) or placebo (PLA) supplementation occurred over 7 days with a 1-week washout between conditions. On the morning of day seven of each supplementation condition, participants consumed one final serving of BLN or PLA and performed a 30-min cycling TT with concurrent assessment of several physiological variables and blood markers. RESULTS: BLN supplementation improved average absolute power compared to PLA (231.6 ± 36.2 vs. 225.3 ± 35.8 W, p = 0.050, d = 0.02). Average relative power, distance traveled, blood parameters (e.g., pH, lactate, glucose, NOx) and inflammatory markers (e.g., IL-6, IL-8, IL-10, TNFα) were not significantly different between conditions. BLN supplementation significantly improved exercise efficiency (W/ml/kg/min) in the last 5 min of the TT compared to PLA (p = 0.029, d = 0.45). Brachial artery blood flow in the BLN condition, immediately post-exercise, tended to be greater compared to PLA (p = 0.065, d = 0.32). CONCLUSIONS: We report that 7 days of BLN supplementation modestly improves 30-min TT power output, exercise efficiency as well as post-exercise blood flow without increasing plasma NOx levels or altering blood markers of inflammation, oxidative stress, and/or hematopoiesis.

Concomitant external pneumatic compression treatment with consecutive days of high intensity interval training reduces markers of proteolysis.

PURPOSE: To compare the effects of external pneumatic compression (EPC) and sham when used concurrently with high intensity interval training (HIIT) on performance-related outcomes and recovery-related molecular measures. METHODS: Eighteen recreationally endurance-trained male participants (age: 21.6 ± 2.4 years, BMI: 25.7 ± 0.5 kg/m2, VO2peak: 51.3 ± 0.9 mL/kg/min) were randomized to balanced sham and EPC treatment groups. Three consecutive days of HIIT followed by EPC/sham treatment (Days 2-4) and 3 consecutive days of recovery (Days 5-7) with EPC/sham only on Days 5-6 were employed. Venipuncture, flexibility and pressure-to-pain threshold (PPT) measurements were made throughout. Vastus lateralis muscle was biopsied at PRE (i.e., Day 1), 1-h post-EPC/sham treatment on Day 2 (POST1), and 24-h post-EPC/sham treatment on Day 7 (POST2). 6-km run time trial performance was tested at PRE and POST2. RESULTS: No group × time interaction was observed for flexibility, PPT, or serum measures of creatine kinase (CK), hsCRP, and 8-isoprostane. However, there was a main effect of time for serum CK (p = 0.005). Change from PRE in 6-km run times at POST2 were not significantly different between groups. Significant between-groups differences existed for change from PRE in atrogin-1 mRNA (p = 0.018) at the POST1 time point (EPC: - 19.7 ± 8.1%, sham: + 7.7 ± 5.9%) and atrogin-1 protein concentration (p = 0.013) at the POST2 time point (EPC: - 31.8 ± 7.5%, sham: + 96.0 ± 34.7%). In addition, change from PRE in poly-Ub proteins was significantly different between groups at both the POST1 (EPC: - 26.0 ± 10.3%, sham: + 34.8 ± 28.5%; p = 0.046) and POST2 (EPC: - 33.7 ± 17.2%, sham: + 21.4 ± 14.9%; p = 0.037) time points. CONCLUSIONS: EPC when used concurrently with HIIT and in subsequent recovery days reduces skeletal muscle markers of proteolysis.

Whey protein-derived exosomes increase protein synthesis and hypertrophy in C2-C12 myotubes.

We sought to examine potential amino acid independent mechanisms whereby hydrolyzed whey protein (WP) affects muscle protein synthesis (MPS) and anabolism in vitro. Specifically, we tested (1) whether 3-h and 6-h treatments of WP, essential amino acids, or l-leucine (Leu) affected MPS, and whether 6-h treatments with low-, medium-, or high doses of WP versus Leu affected MPS; (2) whether knockdown of the primary Leu transporter affected WP- and Leu-mediated changes in MPS, mammalian target of rapamycin (mTOR) signaling responses, or both, following 6-h treatments; (3) whether exosomes isolated from WP (WP-EXO) affected MPS, mTOR signaling responses, or both, compared with untreated (control) myotubes, following 6-h, 12-h, and 24-h treatments, and whether they affected myotube diameter following 24-h and 48-h treatments. For all treatments, 7-d post-differentiated C2C12 myotubes were examined. In experiment 1, 6-h WP treatments increased MPS compared with control (+46%), Leu (+24%), and essential amino acids (+25%). Moreover, the 6-h low-, medium-, and high WP treatments increased MPS by approximately 40 to 50% more than corresponding Leu treatments. In experiment 2 (LAT short hairpin RNA-transfected myotubes), 6-h WP treatments increased MPS compared with control (+18%) and Leu (+19%). In experiment 3, WP-EXO treatments increased MPS over controls at 12h (+18%) and 24h (+45%), and myotube diameters increased with 24-h (+24%) and 48-h (+40%) WP-EXO treatments compared with controls. The WP-EXO treatments did not appear to operate through mTOR signaling; instead, they increased mRNA and protein levels o eukaryotic initiation factor 4A. Bovine-specific microRNA following 24-h WP-EXO treatments were enriched in myotubes (chiefly miR-149-3p, miR-2881), but were not related to hypertrophic gene targets. To summarize, hydrolyzed WP-EXO increased skeletal MPS and anabolism in vitro, and this may be related to an unknown mechanism that increases translation initiation factors rather than enhancing mTOR signaling or the involvement of bovine-specific microRNA.

Comparative effects of whey protein versus L-leucine on skeletal muscle protein synthesis and markers of ribosome biogenesis following resistance exercise.

We compared immediate post-exercise whey protein (WP, 500 mg) versus L-leucine (LEU, 54 mg) feedings on skeletal muscle protein synthesis (MPS) mechanisms and ribosome biogenesis markers 3 h following unilateral plantarflexor resistance exercise in male, Wistar rats (~250 g). Additionally, in vitro experiments were performed on differentiated C2C12 myotubes to compare nutrient (i.e., WP, LEU) and 'exercise-like' treatments (i.e., caffeine, hydrogen peroxide, and AICAR) on ribosome biogenesis markers. LEU and WP significantly increased phosphorylated-rpS6 (Ser235/236) in the exercised (EX) leg 2.4-fold (P < 0.01) and 2.7-fold (P < 0.001) compared to the non-EX leg, respectively, whereas vehicle-fed control (CTL) did not (+65 %, P > 0.05). Compared to the non-EX leg, MPS levels increased 32 % and 52 % in the EX leg of CTL (P < 0.01) and WP rats (P < 0.001), respectively, but not in LEU rats (+15 %, P > 0.05). Several genes associated with ribosome biogenesis robustly increased in the EX versus non-EX legs of all treatments; specifically, c-Myc mRNA, Nop56 mRNA, Bop1 mRNA, Ncl mRNA, Npm1 mRNA, Fb1 mRNA, and Xpo-5 mRNA. However, only LEU significantly increased 45S pre-rRNA levels in the EX leg (63 %, P < 0.001). In vitro findings confirmed that 'exercise-like' treatments similarly altered markers of ribosome biogenesis, but only LEU increased 47S pre-rRNA levels (P < 0.01). Collectively, our data suggests that resistance exercise, as well as 'exercise-like' signals in vitro, acutely increase the expression of genes associated with ribosome biogenesis independent of nutrient provision. Moreover, while EX with or without WP appears superior for enhancing translational efficiency (i.e., increasing MPS per unit of RNA), LEU administration (or co-administration) may further enhance ribosome biogenesis over prolonged periods with resistance exercise.

Ten weeks of branched-chain amino acid supplementation improves select performance and immunological variables in trained cyclists.

We examined if supplementing trained cyclists (32 ± 2 year, 77.8 ± 2.6 kg, and 7.4 ± 1.2 year training) with 12 g/day (6 g/day L-Leucine, 2 g/day L-Isoleucine and 4 g/day L-Valine) of either branched-chain amino acids (BCAAs, n = 9) or a maltodextrin placebo (PLA, n = 9) over a 10-week training season affected select body composition, performance, and/or immune variables. Before and after the 10-week study, the following was assessed: (1) 4-h fasting blood draws; (2) dual X-ray absorptiometry body composition; (3) Wingate peak power tests; and (4) 4 km time-trials. No group × time interactions existed for total lean mass (P = 0.27) or dual-leg lean mass (P = 0.96). A significant interaction existed for body mass-normalized relative peak power (19 % increase in the BCAA group pre- to post-study, P = 0.01), and relative mean power (4 % increase in the BCAA group pre- to post-study, P = 0.01). 4 km time-trial time to completion approached a significant interaction (P = 0.08), as the BCAA group improved in this measure by 11 % pre- to post-study, though this was not significant (P = 0.15). There was a tendency for the BCAA group to present a greater post-study serum BCAA: L-Tryptophan ratio compared to the PLA group (P = 0.08). A significant interaction for neutrophil number existed (P = 0.04), as there was a significant 18 % increase within the PLA group from the pre- to post-study time point (P = 0.01). Chronic BCAA supplementation improves sprint performance variables in endurance cyclists. Additionally, given that BCAA supplementation blunted the neutrophil response to intense cycling training, BCAAs may benefit immune function during a prolonged cycling season.

Differential vascular reactivity responses acutely following ingestion of a nitrate rich red spinach extract.

INTRODUCTION: Inorganic nitrate ingestion has been posited to affect arterial blood pressure and vascular function. PURPOSE: We sought to determine the acute effect of a red spinach extract (RSE) high in inorganic nitrate on vascular reactivity 1-h after ingestion in peripheral conduit and resistance arteries. METHODS: Fifteen (n = 15; males 8, females 7) apparently healthy subjects (aged 23.1 ± 3.3 years; BMI 27.2 ± 3.7 kg/m2) participated in this crossover design, double-blinded study. Subjects reported to the lab ≥2-h post-prandial and consumed RSE (1000 mg dose; ~90 mg nitrate) or placebo (PBO). Venipuncture was performed on three occasions: baseline, 30-min post-ingestion and between 65 to 75-min post-ingestion. Baseline vascular measurements [i.e., calf venous occlusion plethysmography, brachial artery flow-mediated dilation (FMD)], 30-min of continuous blood pressure (BP) and heart rate (HR) analysis, and follow-up vascular measurements beginning at 40-min post-ingestion were also performed. RESULTS: Humoral nitrate following RSE ingestion was significantly higher at 30- (+54 %; P = 0.039) and 65 to 75-min post-ingestion compared to baseline (+255 %, P < 0.001) and PBO at the same time points (P < 0.05). No significant changes in BP or HR occurred in either condition. Peak reactive hyperemia (RH) calf blood flow increased significantly (+13.7 %; P = 0.016) following RSE ingestion, whereas it decreased (-14.0 %; P = 0.008) following PBO ingestion. No significant differential FMD responses were detected (P > 0.05), though RH was decreased following the baseline measure in both conditions. CONCLUSIONS: RSE significantly increased plasma nitrate 30-min post-ingestion, but acute microvascular (i.e., resistance vasculature) reactivity increases were isolated to the lower limb and no appreciable change in brachial artery FMD was observed.

A single bout of whole-leg, peristaltic pulse external pneumatic compression upregulates PGC-1α mRNA and endothelial nitric oxide sythase protein in human skeletal muscle tissue.

NEW FINDINGS: What is the central question of this study? Does 60 min of peristaltic pulse external pneumatic compression (EPC) alter gene and protein expression patterns related to metabolism, vascular biology, redox balance and inflammation in vastus lateralis biopsy samples? What is the main finding and its importance? A single bout of EPC transiently upregulates PGC-1α mRNA, while also upregulating endothelial nitric oxide synthase protein and nitric oxide metabolite concentrations in vastus lateralis biopsy samples. We investigated whether a single 60 min bout of whole-leg, lower pressure external pneumatic compression (EPC) altered select vascular, metabolic, antioxidant and inflammation-related mRNAs. Ten participants (eight male, two female; aged 22.0 ± 0.4 years) reported to the laboratory 4 h postprandial, and vastus lateralis muscle biopsies were obtained before (PRE) and 1 and 4 h after EPC treatment. Messenger RNA expression was analysed using real-time RT-PCR, and significant mRNA findings were investigated further by Western blot analysis of respective protein concentrations. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA increased by 77% 1 h following EPC compared with PRE levels (P = 0.005), but no change in protein concentration 1 or 4 h post-EPC was observed. Increases in endothelial nitric oxide sythase (eNOS) mRNA (+44%) and superoxide dismutase 2 (SOD2) mRNA (+57%) 1 h post-EPC as well as an increase in interleukin-10 mRNA (+132%) 4 h post-EPC compared with PRE levels were observed, but only approached significance (P = 0.076, 0.077 and 0.074, respectively). Interestingly, eNOS protein (+40%, P = 0.025) and nitrate and nitrite (NOx) concentrations (+69%, P = 0.025) increased 1-4 h post-EPC. Moreover, SOD2 protein tended to increase from PRE to 4 h post-EPC (+43%, P = 0.074), although no changes in tissue 4-hydroxnonenal levels was observed. An acute bout of EPC transiently upregulates PGC-1α mRNA, while also upregulating eNOS protein and NOx concentrations in vastus lateralis biopsy samples. Future research should characterize the origin of these responses (e.g. vascular or muscle fibre cells) and how the acute effects of EPC application on gene and protein expression observed herein are associated with functional improvements (e.g. metabolism, vascular function) in acute and chronic models.

Enhanced external counterpulsation reduces indices of central blood pressure and myocardial oxygen demand in patients with left ventricular dysfunction.

Enhanced external counterpulsation (EECP) therapy decreases angina episodes and improves quality of life in patients with left ventricular (LV) dysfunction. However, the underlying mechanisms relative to the benefits of EECP therapy in patients with LV dysfunction have not been fully elucidated. The purpose of this study was to investigate the effects of EECP on indices of central haemodynamics, aortic pressure wave reflection characteristics, and estimates of LV load and myocardial oxygen demand in patients with LV dysfunction. Patients with chronic stable angina and LV ejection fraction < 40% but > 30%, were randomized to either an EECP group (LV ejection fraction = 35.1 ± 4.6%; n = 10) or sham-EECP group (LV ejection fraction = 34.3 ± 4.2%; n = 7). Pulse wave analysis of the central aortic pressure waveform and LV function were evaluated by applanation tonometry before and after 35 1-h sessions of EECP or sham-EECP. Enhanced external counterpulsation therapy was effective in reducing indices of LV wasted energy and myocardial oxygen demand by 25% and 19%, respectively. In addition, indices of coronary perfusion pressure and subendocardial perfusion were increased by 9% and 30%, respectively, after EECP. Our data indicate that EECP may be useful as adjuvant therapy for improving functional classification in heart failure patients through reductions in central blood pressure, aortic pulse pressure, wasted LV energy, and myocardial oxygen demand, which also suggests improvements in ventricular-vascular interactions.

Peripheral conduit and resistance artery function are improved following a single, 1-h bout of peristaltic pulse external pneumatic compression.

INTRODUCTION: External pneumatic compression (EPC) is being employed for a widening range of clinical and non-clinical populations. However, EPC devices vary markedly in treatment pressures, duty cycles and application sites, and the acute effects of whole limb, lower pressure EPC on peripheral vascular function have not been determined. PURPOSE: The purpose of this study was to determine the acute effects of a single bout of peristaltic pulse EPC on peripheral conduit and resistance artery function. METHODS: Twenty (n = 20; males = 12 and females = 8) young and apparently healthy subjects (aged 26.1 ± 8.2 years) participated in this study. A sequential EPC device with five inflation zones arranged linearly and inflating distal to proximal along the lower limbs was employed with target inflation pressures of 70 mmHg for 1 h. Flow-mediated dilation (FMD) of the brachial and popliteal arteries was evaluated with ultrasound before and after EPC. Venous occlusion plethysmography was employed to evaluate limb blood flow at rest and during reactive hyperemia (RH) in the forearm (FBF) and calf (CBF) before and after EPC. RESULTS: Peak RH CBF was increased by 9 % after EPC (P < 0.05), whereas peak RH FBF (-10 %) did not change significantly (P > 0.25). Normalized popliteal artery FMD post-EPC (2.24 ± 1.41) was significantly higher than pre-EPC (1.36 ± 0.67, P = 0.015) and post-sham (1.58 ± 0.86, P = 0.032) values. Similarly, normalized brachial artery FMD post-EPC (1.47 ± 0.32) was significantly higher than pre-EPC (1.11 ± 0.41, P = 0.004) and post-sham (0.99 ± 0.27, P = 0.026) values. CONCLUSION: Acutely, whole limb, lower pressure EPC improves conduit artery endothelial function systemically, but only improves RH blood flow locally (i.e., compressed limbs).

Acute Effects of Peristaltic Pneumatic Compression on Repeated Anaerobic Exercise Performance and Blood Lactate Clearance.

External pneumatic compression (EPC) use in athletics is increasing. However, there is a paucity of evidence supporting the effectiveness of EPC in aiding recovery and performance. We sought to determine the efficacy of EPC for acute recovery of anaerobic power and lactate clearance following a fatigue protocol. Fourteen (n = 14; women = 7 and men = 7), apparently healthy, active subjects (aged 22.73 ± 4.05 years) were enrolled in this randomized crossover design study. After familiarization sessions, subjects completed 2 study trials separated by 3-7 days. Trials consisted of a fatigue protocol (two 30-second Wingate anaerobic tests (WAnTs) on a cycle ergometer separated by 3 minutes of rest), 30 minutes of treatment with EPC or sham, and, finally, a single 30-second WAnT. A peristaltic pulse EPC device was used with target inflation pressures of ∼70 mm Hg applied to the lower limbs. Peak power (PkP), average power (AP), and the fatigue index (FI) were recorded for each WAnT. Moreover, blood lactate concentration (BLa) was evaluated at baseline and at regular intervals during recovery (5, 15, 25, and 35 minutes postfatigue protocol). No significant differences in PkP, AP, and FI were observed. However, BLa was significantly lower at 25 and 35 minutes of recovery (8.91 ± 3.12 vs. 10.66 ± 3.44 mmol·L(-1) [p = 0.021] and 6.44 ± 2.14 vs. 7.89 ± 2.37 mmol·L(-1) [p = 0.006] for EPC vs. sham, respectively). Application of EPC during recovery may be a viable alternative when "inactive" recovery is desirable.

Identification of genes whose expression is altered by obesity throughout the arterial tree.

We used next-generation RNA sequencing (RNA-Seq) technology on the whole transcriptome to identify genes whose expression is consistently affected by obesity across multiple arteries. Specifically, we examined transcriptional profiles of the iliac artery as well as the feed artery, first, second, and third branch order arterioles in the soleus, gastrocnemius, and diaphragm muscles from obese Otsuka Long-Evans Tokushima Fatty (OLETF) and lean Long-Evans Tokushima Otsuka (LETO) rats. Within the gastrocnemius and soleus muscles, the number of genes differentially expressed with obesity tended to increase with increasing branch order arteriole number (i.e., decreasing size of the artery). This trend was opposite in the diaphragm. We found a total of 15 genes that were consistently upregulated with obesity (MIS18A, CTRB1, FAM151B, FOLR2, PXMP4, OAS1B, SREBF2, KLRA17, SLC25A44, SNX10, SLFN3, MEF2BNB, IRF7, RAD23A, LGALS3BP) and five genes that were consistently downregulated with obesity (C2, GOLGA7, RIN3, PCP4, CYP2E1). A small fraction (∼9%) of the genes affected by obesity was modulated across all arteries examined. In conclusion, the present study identifies a select number of genes (i.e., 20 genes) whose expression is consistently altered throughout the arterial network in response to obesity and provides further insight into the heterogeneous vascular effects of obesity. Although there is no known direct function of the majority of 20 genes related to vascular health, the obesity-associated upregulation of SREBF2, LGALS3BP, IRF7, and FOLR2 across all arteries is suggestive of an unfavorable vascular phenotypic alteration with obesity. These data may serve as an important resource for identifying novel therapeutic targets against obesity-related vascular complications.

Musculoskeletal and prostate effects of combined testosterone and finasteride administration in older hypogonadal men: a randomized, controlled trial.

Testosterone acts directly at androgen receptors and also exerts potent actions following 5α-reduction to dihydrotestosterone (DHT). Finasteride (type II 5α-reductase inhibitor) lowers DHT and is used to treat benign prostatic hyperplasia. However, it is unknown whether elevated DHT mediates either beneficial musculoskeletal effects or prostate enlargement resulting from higher-than-replacement doses of testosterone. Our purpose was to determine whether administration of testosterone plus finasteride to older hypogonadal men could produce musculoskeletal benefits without prostate enlargement. Sixty men aged ≥60 yr with a serum testosterone concentration of ≤300 ng/dl or bioavailable testosterone ≤70 ng/dl received 52 wk of treatment with testosterone enanthate (TE; 125 mg/wk) vs. vehicle, paired with finasteride (5 mg/day) vs. placebo using a 2 × 2 factorial design. Over the course of 12 mo, TE increased upper and lower body muscle strength by 8-14% (P = 0.015 to <0.001), fat-free mass 4.04 kg (P = 0.032), lumbar spine bone mineral density (BMD) 4.19% (P < 0.001), and total hip BMD 1.96% (P = 0.024) while reducing total body fat -3.87 kg (P < 0.001) and trunk fat -1.88 kg (P = 0.0051). In the first 3 mo, testosterone increased hematocrit 4.13% (P < 0.001). Coadministration of finasteride did not alter any of these effects. Over 12 mo, testosterone also increased prostate volume 11.4 cm(3) (P = 0.0051), an effect that was completely prevented by finasteride (P = 0.0027). We conclude that a higher-than-replacement TE combined with finasteride significantly increases muscle strength and BMD and reduces body fat without causing prostate enlargement. These results demonstrate that elevated DHT mediates testosterone-induced prostate enlargement but is not required for benefits in musculoskeletal or adipose tissue.

Differential vasomotor effects of insulin on gastrocnemius and soleus feed arteries in the OLETF rat model: role of endothelin-1.

The vascular actions of insulin are complex, because it can stimulate both nitric oxide-mediated dilatation and endothelin (ET)-1-mediated constriction. We examined vasoreactivity to insulin in isolated feed arteries of the gastrocnemius (GFA) and soleus muscles (SFA) of 32-week-old Long-Evans Tokushima Otsuka (LETO) and Otsuka Long-Evans Tokushima fatty (OLETF) rats, a hyperphagic rodent model of obesity and insulin resistance. The insulin-induced vasoreactivity of SFA and GFA was similar in LETO (healthy) and OLETF (obese/insulin-resistant) rats. However, examination of between-vessel effects revealed a number of novel insights into the heterogeneous vascular effects of insulin. Soleus feed arteries dilated more than GFA in LETO at 100 and 1000 µIU ml(-1) insulin (23 versus 6 and 28 versus 0%, respectively; P < 0.05 for between-vessel differences). Likewise, in OLETF rats there was significantly greater dilatation in SFA than GFA at 10, 100 and 1000 µIU ml(-1) insulin (28 versus 3, 30 versus 0 and 34 versus 0%, respectively; all P < 0.05). In the presence of 3 µm tezosentan, a non-specific endothelin-1 receptor blocker, insulin-induced dilatation of the GFA was enhanced such that differences between vessels were largely abolished in both groups. Furthermore, acetylecholine-induced dilatation was significantly greater in SFA than GFA within each group, whereas sodium nitroprusside-induced dilatory responses were greater in the GFA compared with the SFA. Overall, our findings indicate that the insulin/endothelin-1 vasoconstrictor pathway is more active in GFA than in SFA, independent of obesity in the OLETF rat model.

Enhanced external counterpulsation improves endothelial function and exercise capacity in patients with ischaemic left ventricular dysfunction.

Enhanced external counterpulsation (EECP) therapy decreases angina episodes and improves quality of life in patients with left ventricular (LV) dysfunction (LVD). However, studies have not elucidated the mechanisms of action and overall effects of EECP in patients with LVD. The purpose of the present study was to investigate the effects of EECP on endothelial function in peripheral conduit arteries and exercise capacity (peak Vo2 ) in patients with LVD. Patients with ischaemic LVD (ejection fraction (EF) 34.5 ± 4.2%; n = 9) and patients with symptomatic coronary artery disease (CAD) and preserved LV function (EF 53.5 ± 6.6%; n = 15) were studied before and after 35 sessions (1 h) of EECP. Brachial and femoral artery flow-mediated dilation (bFMD and fFMD, respectively) were evaluated using high-resolution ultrasound. Enhanced external counterpulsation elicited similar significant improvements in the following FMD parameters in the CAD and LVD groups (P ≥ 0.05 between groups for all): absolute bFMD (+53% and +70%, respectively), relative bFMD (+50% and +74%, respectively), bFMD normalized for shear rate (+70% and +61%, respectively), absolute fFMD (+33% and +21%, respectively) and relative fFMD (+32% and +17%, respectively). In addition, EECP significantly improved plasma levels of nitrate/nitrite (+55% and +28%) and prostacyclin (+50% and +70%), as well as peak Vo2 (+36% and +21%), similarly in both the CAD and LVD groups (P ≥ 0.05 between groups for all). Despite reduced LV function, EECP therapy significantly improves peripheral vascular function and functional capacity in CAD patients with ischaemic LVD to a similar degree to that seen in CAD patients with preserved LV function.