The physiological flux of oxygen is extreme in exercising skeletal muscle. Hypoxia thus a critical parameter muscle function, influencing production ATP, utilization energy-producing substrates, and manufacture exhaustion-inducing metabolites. Glycolysis the central source anaerobic energy animals, this metabolic pathway regulated under low-oxygen conditions by transcription factor hypoxia-inducible 1alpha (HIF-1alpha). To determine role HIF-1alpha regulating we tissue-specifically deleted...

The protein deacetylase, sirtuin 1 (SIRT1), is a proposed master regulator of exercise-induced mitochondrial biogenesis in skeletal muscle, primarily via its ability to deacetylate and activate peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). To investigate regulation by SIRT1 vivo, we generated mice lacking deacetylase activity muscle (mKO). We hypothesized that deacetylation PGC-1α sedentary after endurance exercise would be impaired mKO mice. Skeletal contractile...

Vascular endothelial growth factor (VEGF) is required for vasculogenesis and angiogenesis during embryonic early postnatal life. However the organ-specific functional role of VEGF in adult life, particularly skeletal muscle, less clear. To explore this issue, we engineered muscle-targeted deficient mice (mVEGF-/-) by crossbreeding that selectively express Cre recombinase muscle under control creatine kinase promoter (MCKcre mice) with having a floxed gene (VEGFLoxP mice). We hypothesized...

Proponents for electronic cigarettes (E-cigs) claim that they are a safe alternative to tobacco-based cigarettes; however, little is known about the long-term effects of exposure E-cig vapor on vascular function. The purpose this study was determine cardiovascular consequences chronic exposure. Female mice (C57BL/6 background strain) were randomly assigned daily vapor, standard (3R4F reference) cigarette smoke, or filtered air ( n = 15/group). Respective whole body exposures consisted four...

We have previously shown, using a Cre-LoxP strategy, that vascular endothelial growth factor (VEGF) is required for the development and maintenance of skeletal muscle capillarity in sedentary adult mice. To determine whether VEGF expression capillary adaptation to exercise training, gastrocnemius was measured myocyte-specific gene-deleted (mVEGF(-/-)) wild-type (WT) littermate mice following 6 wk treadmill running (1 h/day, 5 days/wk) at same speed. The effect training on metabolic enzyme...

The metabolic syndrome (MetS) is associated with a threefold increase risk of cardiovascular disease (CVD) mortality partly due to increased arterial stiffening. We compared the effects aerobic exercise training on stiffening/mechanics in MetS subjects without overt CVD or type 2 diabetes. and healthy control (Con) underwent 8 wk (ExT; 11 Con) remained inactive (11 10 Con). following measures were performed pre- postintervention: radial pulse wave analysis (applanation tonometry) was used...

Abstract Gastric cancer is the fifth most common and leading cause of deaths worldwide. Chronic infection by bacterium Helicobacter pylori prominent gastric risk factor, but only 1-3% infected individuals will develop cancer. Cigarette smoking another independent H. pylori-infected smokers are at a 2-11-fold increased development, direct impacts cigarette smoke on pathogenesis remain unknown. In this study, male C57BL/6 mice were with began within one week infection. The exposed to (CS) five...

During endurance training, exercising skeletal muscle experiences severe and repetitive oxygen stress. The primary transcriptional response factor for acclimation to hypoxic stress is hypoxia-inducible factor-1alpha (HIF-1alpha), which upregulates glycolysis angiogenesis in low levels of tissue oxygenation. To examine the role HIF-1alpha we have created mice specifically lacking subjected them an training protocol. We found that only wild-type improve their oxidative capacity, as measured by...

Thrombospondin‐1 (TSP‐1) is a known inhibitor of angiogenesis; however, skeletal muscle phenotype TSP‐1 null mice has not been investigated. The purposes this study were to compare and contrast wild‐type by examining the following: (1) capillarity in cardiac muscles; (2) fibre type composition oxidative enzyme activity hindlimb; (3) consequences gene deletion for exercise capacity. In mice, maximal running speed was 11% greater time exhaustion during submaximal endurance 67% compared with...

The mitochondrion has been implicated in the development of diabetic cardiomyopathy. Examination cardiac mitochondria is complicated by existence spatially distinct subpopulations including subsarcolemmal (SSM) and interfibrillar (IFM). Dysfunction to SSM reported murine models type 2 diabetes mellitus; however, subpopulation-based mitochondrial analyses have not explored human heart. goal this study was determine impact mellitus on function patient. Mitochondrial from atrial appendages...

Epidemiological studies provide strong evidence that obesity and the associated adipose tissue inflammation are risk factors for breast cancer; however, molecular mechanisms poorly understood. We evaluated effect of a high-fat/high-calorie diet on mammary carcinogenesis in immunocompetent MMTV-PyMT murine model. Four-week old female mice (20/group) were randomized to receive either high-fat (HF; 60% kcal as fat) or low-fat (LF; 16% kcal) eight weeks. Body weights determined, tumor volumes...

Exercise-induced arterial hypoxemia (EIAH) has been reported in male athletes, particularly during fast-increment treadmill exercise protocols. Recent reports suggest a higher incidence women. We hypothesized that 1-min incremental (fast) running (R) protocols would result lower Po 2 (Pa O ) than 5-min increment (slow) or cycling (C) and women experience greater EIAH previously for men. Arterial blood gases, cardiac output, metabolic data were obtained 17 active [mean maximal uptake (V˙o max...

Women may experience greater pulmonary gas exchange impairment during exercise than men. To test this we used the multiple inert elimination technique to study eight women and seven men matched for age, height (O(2) max) ( approximately 48 ml x kg(-1) min(-1)) normoxic hypoxic (inspired P(O(2))= 95 Torr) cycle exercise. Resting lung function was similar between sexes, except a lower carbon monoxide diffusing capacity (DL(CO)) in (P < 0.05). Arterial P(O(2)),P(CO(2)) alveolar-arterial O(2)...

Gene expression of vascular endothelial growth factor (VEGF), and to a lesser extent transforming factor-β 1 (TGF-β ) basic fibroblast (bFGF), has been found increase in rat skeletal muscle after single exercise bout. In addition, acute hypoxia augments the VEGF mRNA response exercise, which suggests that, if is important angiogenesis, hypoxic training might produce greater capillary than normoxic training. Therefore, we examined effects (treadmill running at same absolute intensity)...

During maximal exercise, ventilation-perfusion inequality increases, especially in athletes. The mechanism remains speculative. We hypothesized that, if interstitial pulmonary edema is involved, prolonged exercise would result increasing over time by exposing the vascular bed to high pressures for a long duration. response short-term was first characterized six male athletes [maximal O 2 uptake (V˙o max ) = 63 ml ⋅ kg −1 min ] using 5 of cycling at 30, 65, and 90%V˙o . Multiple inert-gas,...

POINT-COUNTERPOINTPoint:Counterpoint: Exercise-induced intrapulmonary shunting is imaginary vs. realSusan R. Hopkins, I. Mark Olfert, and Peter D. WagnerSusan WagnerPublished Online:01 Sep 2009https://doi.org/10.1152/japplphysiol.91489.2008This the final version - click for previous versionMoreSectionsPDF (46 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations POINT: EXERCISE-INDUCED INTRAPULMONARY SHUNTING IS IMAGINARYPulmonary gas exchange efficiency...

Acetazolamide (ACZ) is used to prevent acute mountain sickness at altitude. Because it could affect O2 transport in several different and potentially conflicting ways, we examined its effects on pulmonary muscle gas exchange acid-base status during cycle exercise approximately 30, 50 90% VO2max normoxia (F(IO2) = 0.2093) hypoxia 0.125). In a double-blind, order-balanced, crossover design, six healthy, trained men (normoxic VO2max= 59 ml kg(-1) min(-1)) exercised both F(IO2) values after ACZ...

Angiogenesis is controlled by a balance between positive and negative angiogenic factors, but temporal protein expression of many key regulators in response to exercise are still poorly defined. In C57BL/6 mice, we evaluated the several pro-angiogenic anti-angiogenic factors (1) single acute bout (2) chronic training resulting from 3, 5, 7, 14 28 days voluntary wheel running. Following exercise, levels vascular endothelial growth factor-A (VEGF), endostatin nucleolin were increased at 2-4 h...

The 2010 USDA Dietary Guidelines for Americans (DGA) recommends a diet largely composed of fruit and vegetables. Consuming high in vegetables low refined carbohydrates saturated fat may reduce an individual's risk type 2 diabetes, nonalcoholic fatty liver disease, low-grade chronic inflammation, metabolic syndrome (MetS). Several recent studies have implicated the bioactive sphingolipid ceramide as associative causative biomarker development these conditions. Considering that intake is...

Skeletal muscle anatomy and physiology are sexually dimorphic but molecular underpinnings muscle-specificity not well-established. Variances in metabolic health, fitness level, sedentary behavior, genetics, age make it difficult to discern inherent sex effects humans. Therefore, mice under well-controlled conditions were used determine female male (n = 19/sex) skeletal fiber type/size capillarity superficial deep gastrocnemius (GA-s, GA-d), soleus (SOL), extensor digitorum longus (EDL),...

Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic mitogen. However, chronic hypoxia generally not found to increase mammalian skeletal muscle capillarity. We sought determine the effect of (8 wk, inspired O2 fraction = 0.12) on gene expression VEGF, its receptors (flt-1 and flk-1), basic fibroblast factor, transforming factor-β1. Wistar rats were exposed (n 12) or room air 12). After exposure period, six animals from each group subjected single 1-h treadmill...

Evolution of metabolic syndrome is associated with a progressive reduction in skeletal muscle microvessel density, known as rarefaction. Although contributing to impairments mass transport and exchange, the temporal development rarefaction mechanisms that lead loss are both unclear critical areas for investigation. previous work suggests severity obese Zucker rats (OZR) predicted by chronic vascular nitric oxide (NO) bioavailability, we have determined this hides biphasic rarefaction, early...