bluuebunny/crossref_metadata_2025 huggingface dataset:
Negative energy balance plays a major role in the IGF-I response to exercise training
Authors: Nemet Dan , Connolly Peter H. , Pontello-Pescatello Andria M. , Rose-Gottron Christie , Larson Jennifer K. , Galassetti Pietro , Cooper Dan M.
Published: January 2004

Circulating IGF-I is correlated with fitness, but results of prospective exercise training studies have been inconsistent, showing both increases and decreases in IGF-I. We hypothesized that energy balance, often not accounted for, is a regulating variable such that training plus an energy intake deficit would cause a reduction in IGF-I, whereas training plus energy intake excess would lead to an increased IGF-I. To test this, 19 young, healthy men completed a 7-day strenuous exercise program in which they were randomly assigned to either a positive energy balance [overfed (OF), n = 10] or negative energy balance [underfed (UF), n = 9] group. IGF-I (free and total), insulin, and IGF-binding protein-1 were measured before, during, and 1 wk after the training. Weight decreased in the UF subjects and increased in the OF subjects. Free and total IGF-I decreased substantially in the UF group ( P < 0.0005 for both), but, in the OF group, IGF-I remained unchanged. The UF group also demonstrated an increase in IGF-binding protein-1 ( P < 0.027), whereas glucose levels decreased ( P < 0.0005). In contrast, insulin was reduced in both the OF and UF exercise-training groups ( P < 0.044). Finally, within 7 days of the cessation of the diet and training regimen, IGF-I and IGF-binding protein-1 in the UF group returned to preintervention levels. We conclude that energy balance during periods of exercise training influences circulating IGF-I and related growth mediators. Exercise-associated mechanisms may inhibit increases in IGF-I early in the course of a training protocol, even in overfed subjects.
Effect of training status and exercise mode on endogenous steroid hormones in men
Authors: Tremblay Mark S. , Copeland Jennifer L. , Van Helder Walter
Published: January 2004

The purpose of this study was to determine the acute anabolic and catabolic hormone response to endurance and resistance exercise bouts of equal volume in subjects with differing training status. Twenty-two healthy men were recruited who were either resistance trained ( n = 7), endurance trained ( n = 8), or sedentary ( n = 7). Three sessions were completed: a resting session, a 40-min run at 50-55% maximal oxygen consumption, and a resistance exercise session. Expired gases were monitored continuously during exercise, and the endurance and resistance exercise sessions were individually matched for caloric expenditure. Blood samples were drawn before exercise and 1, 2, 3, and 4 h after the start of the exercise. Plasma was analyzed for luteinizing hormone, dehydroepiandrosterone sulfate, cortisol, and free and total testosterone. Androgens increased in response to exercise, particularly resistance exercise, whereas cortisol only increased after resistance exercise. Dehydroepiandrosterone sulfate levels increased during the resistance exercise session and remained elevated during recovery in the resistance-trained subjects. Endurance-trained subjects displayed less pronounced changes in hormone concentrations in response to exercise than resistance-trained subjects. After an initial postexercise increase, there was a significant decline in free and total testosterone during recovery from resistance exercise ( P < 0.05), particularly in resistance-trained subjects. On the basis of the results of this study, it appears that the endogenous hormone profile of men is more dependent on exercise mode or intensity than exercise volume as measured by caloric expenditure. The relatively catabolic environment observed during the resistance session may indicate an intensity-rather than a mode-dependent response.
On the reflex coactivation of ankle flexor and extensor muscles induced by a sudden drop of support surface during walking in humans
Authors: Nakazawa Kimitaka , Kawashima Noritaka , Akai Masami , Yano Hideo
Published: January 2004

Recent studies have revealed that the stretch reflex responses of both ankle flexor and extensor muscles are coaugmented in the early stance phase of human walking, suggesting that these coaugmented reflex responses contribute to secure foot stabilization around the heel strike. To test whether the reflex responses mediated by the stretch reflex pathway are actually induced in both the ankle flexor and extensor muscles when the supportive surface is suddenly destabilized, we investigated the electromyographic (EMG) responses induced after a sudden drop of the supportive surface at the early stance phase of human walking. While subjects walked on a walkway, the specially designed movable supportive surface was unexpectedly dropped 10 mm during the early stance phase. The results showed that short-latency reflex EMG responses after the impact of the drop (<50 ms) were consistently observed in both the ankle flexor and extensor muscles in the perturbed leg. Of particular interest was that a distinct response appeared in the tibialis anterior muscle, although this muscle showed little background EMG activity during the stance phase. These results indicated that the reflex activities in the ankle muscles certainly acted when the supportive surface was unexpectedly destabilized just after the heel strike during walking. These reflex responses were most probably mediated by the facilitated stretch reflex pathways of the ankle muscles at the early stance phase and were suggested to be relevant to secure stabilization around the ankle joint during human walking.
Regulation of the angiotensin-converting enzyme activity by a time-course hypoxia in the carotid body
Authors: Lam Siu Yin , Fung Man-Lung , Leung Po Sing
Published: January 2004

Chronic hypoxia activates a local angiotensin-generating system in the carotid body. Here, we test the hypothesis that the activity of the critical enzyme for this system, angiotensin-converting enzyme (ACE), in the carotid body is subject to regulation by a time-course hypoxia. Results from the carotid body assays showed that ACE activity was markedly increased under the hypoxic stress of 7-, 14-, 21-, and 28-day exposures. The changes in ACE activity of 7-day (15.00 vs. 30.95 × 10-5 nmol·μg-1·min-1), 14-day (8.73 vs. 30.25 × 10-5 nmol·μg-1·min-1), and 21-day (11.41 vs. 31.83 × 10-5 nmol·μg-1·min-1) hypoxia treatments were enhanced significantly. However, ACE activity in 28-day (13.18 vs. 24.53 × 10-5 nmol·μg-1·min-1) hypoxia treatment was observed to increase insignificantly when compared with results in the respective control groups. Captopril inhibited all rises in ACE activity in both the control and experimental groups. Results clearly indicate an activation of the enzymatic activity of ACE, the critical enzyme for determining the conversion of angiotensin I into the physiologically active angiotensin II, by chronic hypoxia in the carotid body. An increase in the ACE activity may increase the local production of angiotensin II in the carotid body and thus its agonist action at the AT1 receptor. This may be important in the modulation of cardiopulmonary adaptation in the hypoxic ventilatory response as well as for electrolyte and water homeostasis during chronic hypoxia.
Estimation of segmental muscle volume by bioelectrical impedance spectroscopy
Authors: Bartok Cynthia , Schoeller Dale A.
Published: January 2004

This study validated bioelectrical impedance spectroscopy (BIS) with Cole-Cole modeled measurements of calf and arm segmental water volume and volume changes during 72 h of simulated microgravity and caloric restriction by using magnetic resonance imaging (MRI) muscle volume as a criterion method. MRI and BIS measurements of calf and upper arm segments were made in 18 healthy men and women [age, 29 ± 8 (SD) yr; height, 171 ± 11 cm; mass, 71 ± 16 kg] before and after the intervention. Muscle volume of arm and leg segments by MRI was on average 15 ± 10 and 14 ± 8% lower, respectively, than the estimated total water volume by BIS ( P < 0.01), but their correlations were excellent ( r = 0.96 and r = 0.93, respectively). MRI- vs. BIS-predicted volume changes were a decrease of 49 ± 68 vs. 41 ± 62 ml in the calf and a decrease of 18 ± 23 vs. 11 ± 24 ml in the arm, respectively ( P > 0.05 for both). BIS detected the extracellular water shifts in the calf resulting from the head-down tilt treatment, but the underfeeding protocol was not of sufficient duration or intensity to produce limb intracellular water changes detectable by BIS. BIS was highly correlated with segmental muscle volume and tracked changes associated with head-down tilt. Further research, however, is needed to determine whether BIS can accurately access separate changes in intracellular and extracellular volume.
Effects of caffeine on mouse skeletal muscle power output during recovery from fatigue
Authors: James Rob. S. , Wilson Robbie S. , Askew Graham N.
Published: January 2004

The effects of 10 mM (high) and 70 μM (physiologically relevant) caffeine on force, work output, and power output of isolated mouse extensor digitorum longus (EDL) and soleus muscles were investigated in vitro during recovery from fatigue at 35°C. To monitor muscle performance during recovery from fatigue, we regularly subjected the muscle to a series of cyclical work loops. Force, work, and power output during shortening were significantly higher after treatment with 10 mM caffeine, probably as a result of increased Ca2+release from the sarcoplasmic reticulum. However, the work required to relengthen the muscle also increased in the presence of 10 mM caffeine. This was due to a slowing of relaxation and an increase in muscle stiffness. The combination of increased work output during shortening and increased work input during lengthening had different effects on the two muscles. Net power output of mouse soleus muscle decreased as a result of 10 mM caffeine exposure, whereas net power output of the EDL muscle showed a transient, significant increase. Treatment with 70 μM caffeine had no significant effect on force, work, or power output of EDL or soleus muscles, suggesting that the plasma concentrations found when caffeine is used to enhance performance in human athletes might not directly affect the contractile performance of fatigued skeletal muscle.
Branched equation modeling of simultaneous accelerometry and heart rate monitoring improves estimate of directly measured physical activity energy expenditure
Authors: Brage Søren , Brage Niels , Franks Paul W. , Ekelund Ulf , Wong Man-Yu , Andersen Lars Bo , Froberg Karsten , Wareham Nicholas J.
Published: January 2004

The combination of heart rate (HR) monitoring and movement registration may improve measurement precision of physical activity energy expenditure (PAEE). Previous attempts have used either regression methods, which do not take full advantage of synchronized data, or have not used movement data quantitatively. The objective of the study was to assess the precision of branched model estimates of PAEE by utilizing either individual calibration (IC) of HR and accelerometry or corresponding mean group calibration (GC) equations. In 12 men (20.6-25.2 kg/m2), IC and GC equations for physical activity intensity (PAI) were derived during treadmill walking and running for both HR (Polar) and hipacceleration [Computer Science and Applications (CSA)]. HR and CSA were recorded minute by minute during 22 h of whole body calorimetry and converted into PAI in four different weightings (P1-4) of the HR vs. the CSA (1-P1-4) relationships: if CSA > x, we used the P1 weighting if HR > y, otherwise P2. Similarly, if CSA ≤ x, we used P3 if HR > z, otherwise P4. PAEE was calculated for a 12.5-h nonsleeping period as the time integral of PAI. A priori, we assumed P1 = 1, P2 = P3 = 0.5, P4 = 0, x = 5 counts/min, y = walking/running transition HR, and z = flex HR. These parameters were also estimated post hoc. Means ± SD estimation errors of a priori models were -4.4 ± 29 and 3.5 ± 20% for IC and GC, respectively. Corresponding post hoc model errors were -1.5 ± 13 and 0.1 ± 9.8%, respectively. All branched models had lower errors ( P ≤ 0.035) than single-measure estimates of CSA (less than or equal to -45%) and HR (≥39%), as well as their nonbranched combination (≥25.7%). In conclusion, combining HR and CSA by branched modeling improves estimates of PAEE. IC may be less crucial with this modeling technique.
Effect of the volume and intensity of exercise training on insulin sensitivity
Authors: Houmard Joseph A. , Tanner Charles J. , Slentz Cris A. , Duscha Brian D. , McCartney Jennifer S. , Kraus William E.
Published: January 2004

Physical activity enhances insulin action in obese/overweight individuals. However, the exercise prescription required for the optimal enhancement is not known. The purpose of this study was to test the hypothesis that exercise training consisting of vigorous-intensity activity would enhance insulin sensitivity more substantially than moderate-intensity activity. Sedentary, overweight/obese subjects ( n = 154) were randomly assigned to either control or an exercise group for 6 mo: 1) low-volume/moderate-intensity group [∼12 miles walking/wk at 40–55% peak O2 consumption (V̇o2 peak)], 2) low-volume/high-intensity group (∼12 miles jogging/wk at 65–80% V̇o2 peak), and 3) high-volume/high-intensity group (∼20 miles jogging/wk at 65–80% V̇o2 peak). Training volume (miles/wk) was achieved by exercising ∼115 min/wk (low-volume/high-intensity group) or ∼170 min/wk (low-volume/moderate-intensity and high-volume/high-intensity groups). Insulin action was measured with an insulin sensitivity index (SI) from an intravenous glucose tolerance test. In the control group, there was a decrement ( P < 0.05) in SI. In contrast, all the exercise groups significantly ( P < 0.05) increased SI; the relative increment in the low-volume/moderate-intensity and high-volume/high-intensity groups (∼85%) were greater than in the low-volume/high-intensity group (∼40%). In conclusion, physical activity encompassing a wide range of intensity and volume minimizes the insulin resistance that develops with a sedentary lifestyle. However, an exercise prescription that incorporated ∼170 min of exercise/wk improved insulin sensitivity more substantially than a program utilizing ∼115 min of exercise/wk, regardless of exercise intensity and volume. Total exercise duration should thus be considered when designing training programs with the intent of improving insulin action.
Acute exposure to GH during exercise stimulates the turnover of free fatty acids in GH-deficient men
Authors: Kanaley Jill A. , Dall Rolf , Møller Niels , Nielsen Sven C. , Christiansen Jens Sandahl , Jensen Michael D. , Jørgensen Jens Otto Lunde
Published: January 2004

The secretion of growth hormone (GH) increases acutely during exercise, but whether this is associated with the concomitant alterations in substrate metabolism has not previously been studied. We examined the effects of acute GH administration on palmitate, glucose, and protein metabolism before, during, and after 45 min of moderate-intensity aerobic exercise in eight GH-deficient men (mean age = 40.8 ± 2.9 yr) on two occasions, with (+GH; 0.4 IU GH) and without GH administered (-GH). A group of healthy controls ( n = 8, mean age = 40.4 ± 4.2 yr) were studied without GH. The GH replacement during exercise on the +GH study mimicked the endogenous GH profile seen in healthy controls. No significant difference in resting free fatty acid (FFA) flux was found between study days, but during exercise a greater FFA flux was found when GH was administered (211 ± 26 vs. 168 ± 28 μmol/min, P < 0.05) and remained elevated throughout recovery ( P < 0.05). With GH administered, the exercise FFA flux was not significantly different from that observed in control subjects (188 ± 14 μmol/min), but the recovery flux was greater on the +GH day than in the controls (169 ± 17 vs. 119 ± 11 μmol/min, respectively, P < 0.01). A significant time effect ( P < 0.01) for glucose rate of appearance from rest to exercise and recovery occurred in the GH-deficient adults and the controls, whereas there were no differences in glucose rate of disappearance. No significant effect across time was found for protein muscle balance. In conclusion, 1) acute exposure to GH during exercise stimulates the FFA release and turnover in GH-deficient adults, 2) GH does not significantly impact glucose or protein metabolism during exercise, and 3) the exercise-induced secretion of GH plays a significant role in the regulation of fatty acid metabolism.
Acetylcholine release from the carotid body by hypoxia: evidence for the involvement of autoinhibitory receptors
Authors: Kim Dong-Kyu , Prabhakar Nanduri R. , Kumar Ganesh K.
Published: January 2004

The purpose of the present study was to investigate whether hypoxia influences acetylcholine (ACh) release from the rabbit carotid body and, if so, to determine the mechanism(s) associated with this response. ACh is expressed in the rabbit carotid body (5.6 ± 1.3 pmol/carotid body) as evidenced by electrochemical analysis. Immunocytochemical analysis of the primary cultures of the carotid body with antibody specific to ACh further showed that ACh-like immunoreactivity is localized to many glomus cells. The effect of hypoxia on ACh release was examined in ex vivo carotid bodies harvested from anesthetized rabbits. The basal release of ACh during normoxia (∼150 Torr) averaged 5.9 ± 0.5 fmol·min-1·carotid body-1. Lowering the Po2 to 90 and 20 Torr progressively decreased ACh release by ∼15 and ∼68%, respectively. ACh release returned to the basal value on reoxygenation. Simultaneous monitoring of dopamine showed a sixfold increase in dopamine release during hypoxia. Hypercapnia (21% O2 + 10% CO2) as well as high K+ (100 mM) facilitated ACh release from the carotid body, suggesting that hypoxia-induced inhibition of ACh release is not due to deterioration of the carotid body. Hypoxia had no significant effect on acetylcholinesterase activity in the medium, implying that increased hydrolysis of ACh does not account for hypoxia-induced inhibition of ACh release. In the presence of either atropine (10 μM) or domperidone (10 μM), hypoxia stimulated ACh release. These results demonstrate that glomus cells of the rabbit carotid body express ACh and that hypoxia overall inhibits ACh release via activation of muscarinic and dopaminergic autoinhibitory receptors in the carotid body.
HSP90 and Akt modulate Ang-1-induced angiogenesis via NO in coronary artery endothelium
Authors: Chen Jian-xiong , Lawrence Mayme Lee , Cunningham Gary , Christman Brian W. , Meyrick Barbara
Published: January 2004

This study examines the notion that heat shock protein (HSP) 90 binding to nitric oxide (NO), endothelial NO synthase (eNOS), and PI3K-Akt regulate angiopoietin (Ang)-1-induced angiogenesis in porcine coronary artery endothelial cells (PCAEC). Exposure to Ang-1 (250 ng/ml) for periods up to 2 h resulted in a time-dependent increase in eNOS phosphorylation at Ser 1177 that occurred by 5 min and peaked at 60 min. This was accompanied by a gradual increase in NO release. Ang-1 also led to stimulation of HSP90 binding to eNOS and a significant increase in Akt phosphorylation. Thirty minutes of pretreatment of cells with either 1 μg/ml geldanamycin (a specific inhibitor of HSP90) or 500 nM wortmannin [a specific phosphatidylinositol 3 (PI3)-kinase (PI3K) inhibitor] significantly attenuated Ang-1-stimulated eNOS phosphorylation and NO production. Exposure to Ang-1 caused an increase in endothelial cell migration, tube formation, and sprouting from PCAEC spheroids, and pharmacological blockage of HSP90 function or inhibition of PI3K-Akt pathway completely abolished these effects. Inhibition of nitric oxide synthase by NG-nitro-l-arginine methyl ester (2.5 mM) also resulted in a significant decrease in Ang-1-induced angiogenesis. We conclude that stimulated HSP90 binding to eNOS and activation of the PI3-Akt pathway contribute to Ang-1-induced eNOS phosphorylation, NO production, and angiogenesis in PCAEC.
Altered regional blood flow responses to submaximal exercise in older rats
Authors: Musch Timothy I. , Eklund Kevin E. , Hageman K. Sue , Poole David C.
Published: January 2004

Maximal aerobic capacity and the ability to sustain submaximal exercise (Ex) declines with advancing age. Whether altered muscle blood flow (BF) plays a mechanistic role in these effects remains to be resolved. The present investigation determined the effects of aging on the hemodynamic and regional BF response to submaximal Ex in rats. Heart rate (HR), mean arterial pressure (MAP), and BF to different organs (kidneys, splanchnic organs, and 28 hindlimb muscles) were determined at rest and during submaximal treadmill Ex (20 m/min, 5% grade) with radiolabeled microspheres in young (Y; 6-8 mo old, 339 ± 8 g, n = 9) and old (O; 27-29 mo old, 504 ± 18 g, n = 7) Fischer 344 × Brown Norway rats. Results demonstrated that HR, MAP, and BF to the pancreas, small and large intestine, and total hindlimb musculature were similar between Y and O rats at rest. BF to the kidneys, spleen, and stomach were 33, 60, and 43% lower, respectively, in O compared with Y rats. BF to the total hindlimb musculature increased ( P < 0.05) during Ex and was similar for both Y and O rats (Y: 16 ± 3 to 124 ± 7 vs. O: 20 ± 3 to 137 ± 12 ml·min-1·100 g-1). However, in O vs. Y rats, BF was reduced in 6 (highly oxidative) and elevated in 8 (highly glycolytic) of the 28 individual hindquarter muscles or muscle parts examined ( P < 0.05). During Ex, BF to the spleen and stomach decreased ( P < 0.05) from rest in Y rats, whereas BF decreased in the kidneys, pancreas, spleen, stomach, as well as the small and large intestines of O rats. In conclusion, these data demonstrate that, despite similar increases in total hindlimb BF in Y and O rats during submaximal Ex, there is a profound BF redistribution from highly oxidative to highly glycolytic muscles.
Coordination of intrinsic and extrinsic tongue muscles during spontaneous breathing in the rat
Authors: Bailey E. F. , Fregosi R. F.
Published: January 2004

The muscular-hydrostat model of tongue function proposes a constant interaction of extrinsic (external bony attachment, insertion into base of tongue) and intrinsic (origin and insertion within the tongue) tongue muscles in all tongue movements (Kier WM and Smith KK. Zool J Linn Soc 83: 207-324, 1985). Yet, research that examines the respiratory-related effects of tongue function in mammals continues to focus almost exclusively on the respiratory control and function of the extrinsic tongue protrusor muscle, the genioglossus muscle. The respiratory control and function of the intrinsic tongue muscles are unknown. Our purpose was to determine whether intrinsic tongue muscles have a respiration-related activity pattern and whether intrinsic tongue muscles are coactivated with extrinsic tongue muscles in response to respiratory-related sensory stimuli. Esophageal pressure and electromyographic (EMG) activity of an extrinsic tongue muscle (hyoglossus), an intrinsic tongue muscle (superior longitudinal), and an external intercostal muscle were studied in anesthetized, tracheotomized, spontaneously breathing rats. Mean inspiratory EMG activity was compared at five levels of inspired CO2. Intrinsic tongue muscles were often quiescent during eupnea but active during hypercapnia, whereas extrinsic tongue muscles were active in both eupnea and hypercapnia. During hypercapnia, the activities of the airway muscles were largely coincident, although the onset of extrinsic muscle activity generally preceded the onset of intrinsic muscle activation. Our findings provide evidence, in an in vivo rodent preparation, of respiratory modulation of motoneurons supplying intrinsic tongue muscles. Distinctions noted between intrinsic and extrinsic activities could be due to differences in motoneuron properties or the central, respiration-related control of each motoneuron population.
Mathematical description of geometric and kinematic aspects of smooth muscle plasticity and some related morphometrics
Authors: Lambert R. K. , Paré P. D. , Seow C. Y.
Published: January 2004

Despite considerable investigation, the mechanisms underlying the functional properties of smooth muscle are poorly understood. This can be attributed, at least in part, to a lack of knowledge about the structure and organization of the contractile apparatus inside the muscle cell. Recent observations of the plasticity of smooth muscle and of morphometry of the cell have provided enough information for us to propose a quantitative, although highly simplified, model for the geometric arrangement of contractile units and their collective kinematic functions in smooth muscle, particularly airway smooth muscle. We propose that, to a considerable extent, contractile machinery restructures upon activation of the muscle and adapts to cell geometry at the time of activation. We assume that, under steady-state conditions, the geometric arrangement of contractile units and the filaments within these units determines the kinematic characteristics of the muscle. The model successfully predicts the results of experiments on airway smooth muscle plasticity relating to maximal force generation, maximal velocity of shortening, and the variation of compliance with adapted length. The model is also concordant with morphometric observations that show an increase in myosin filament density when muscle is adapted to a longer length. The model provides a framework for design of experiments to quantitatively test various aspects of smooth muscle plasticity in terms of geometric arrangement of contractile units and the muscle's mechanical properties.
Na+-K+-ATPase in rat skeletal muscle: content, isoform, and activity characteristics
Authors: Fowles J. R. , Green H. J. , Ouyang J.
Published: January 2004

The purpose of this study was to investigate the hypothesis that muscle Na+-K+-ATPase activity is directly related to Na+-K+-ATPase content and the content of the α2-catalytic isoform in muscles of different fiber-type composition. To investigate this hypothesis, tissue was sampled from soleus (Sol), red gastrocnemius (RG), white gastrocnemius (WG), and extensor digitorum longus (EDL) muscles at rest from 38 male Wistar rats weighing 413 ± 6.0 g (mean ± SE). Na+-K+-ATPase activity was determined in homogenates (Hom) and isolated crude membranes (CM) by the regenerating ouabain-inhibitable hydrolytic activity assay (ATPase) and the 3- O-methylfluorescein K+-stimulated phosphatase (3- O-MFPase) assay in vitro. In addition, Na+-K+-ATPase content (Bmax) and the distribution of α1-, α2-, β1-, and β2-isoforms were determined by [3H]ouabain binding and Western blot, respectively. For the ATPase assay, differences ( P < 0.05) in enzyme activity between muscles were observed in Hom (EDL > WG) and in CM (Sol > EDL = WG). For the 3- O-MFPase assay, differences ( P < 0.05) were also found for Hom (Sol > RG = EDL > WG) and CM (Sol = WG > RG). For Bmax, differences in the order of RG = EDL > Sol = WG ( P < 0.05) were observed. Isoform distribution was similar between Hom and CM and indicated in CM, a greater density ( P < 0.05) of α1in Sol than WG and EDL ( P < 0.05), but more equal distribution of α2between muscles. The β1was greater ( P < 0.05) in Sol and RG, and the β2was greater in EDL and WG ( P < 0.05). Over all muscles, the correlation ( r) between Hom 3- O-MFPase and Bmaxwas 0.45 ( P < 0.05) and between Hom α2and Bmax, 0.59 ( P < 0.05). The α1distribution correlated to Hom 3- O-MFPase ( r = 0.79, P < 0.05) CM ATPase ( r = 0.69, P < 0.005) and CM 3- O-MFPase activity ( r = 0.32, P < 0.05). The α2distribution was not correlated with any of the Na+-K+-ATPase activity measurements. The results indicate generally poor relationships between activity and total pump content and α2isoform content of the Na+-K+-ATPase. Several factors, including the type of preparation and the type of assay, appear important in this regard.
Angiogenic growth factor response to acute systemic exercise in human skeletal muscle
Authors: Gavin Timothy P. , Robinson Christopher B. , Yeager Robert C. , England Justin A. , Nifong L. Wiley , Hickner Robert C.
Published: January 2004

We investigated whether acute systemic exercise increases vascular endothelial growth factor (VEGF), VEGF receptor (KDR and Flt-1) mRNA, and VEGF protein in sedentary humans. Twelve sedentary subjects were recruited and performed 1 h of acute, cycle ergometer exercise at 50% of maximal oxygen consumption. Muscle biopsies were obtained from the vastus lateralis before exercise and at 0, 2, and 4 h postexercise. Acute exercise significantly increased VEGF mRNA at 2 and 4 h and increased KDR and Flt-1 mRNA at 4 h postexercise. The sustained increase in VEGF mRNA through 4 h and the increases in KDR and Flt-1 at 4 h are different from their respective time course responses in rats. In contrast to the increase in VEGF mRNA postexercise, VEGF protein levels were decreased at 0 h postexercise. These results provide evidence in humans that 1) VEGF, KDR, and Flt-1 mRNA are increased by acute systemic exercise; 2) the time course of the VEGF, KDR, and Flt-1 mRNA responses are different from those previously reported in rats (Gavin TP and Wagner PD. Acta Physiol Scand 175: 201–209, 2002); and 3) VEGF protein is decreased immediately after exercise.
Whole body insulin resistance in rat offspring of mothers consuming alcohol during pregnancy or lactation: comparing prenatal and postnatal exposure
Authors: Chen Li , Nyomba B. L. Grégoire
Published: January 2004

This study examined the effects of maternal ethanol (EtOH) consumption during pregnancy or lactation on glucose homeostasis in the adult rat offspring. Glucose disposal was determined by minimal model during an intravenous glucose tolerance test in rats that had a small or normal birth weight after EtOH exposure in utero and in rats whose mothers were given EtOH during lactation only. All three EtOH groups had decreased glucose tolerance index and insulin sensitivity index, but their glucose effectiveness was not different from that of controls. In addition, EtOH rat offspring that were small at birth had elevated plasma, liver, and muscle triglyceride levels. The data show that EtOH exposure during pregnancy programs the body to insulin resistance later in life, regardless of birth weight, but that this effect also results in dyslipidemia in growth-restricted rats. In addition, insulin resistance is also evident after EtOH exposure during lactation.
Oxygen sensing: applications in humans
Authors: Cherniack Neil S
Published: January 2004

Our concepts of oxygen sensing have been transformed over the years. We now appreciate that oxygen sensing is not a unique property limited to “chemoreceptors” but is a common property of tissues and that responses to changes in oxygen levels are not static but can change over time. Respiratory responses initiated at the carotid body are modified by the excitatory and depressant effects of hypoxia at the brain and on the pathways connecting the carotid body to the brain. Equally important is that we are beginning to use our understanding of the cellular and molecular pathways triggered by hypoxia and hyperoxia to identify therapeutic targets to treat diseases such as cancer. We also have a better understanding of the complexities of the human respiratory responses to hypoxia; however, major deficiencies remain in our ability to alter or even measure human ventilatory responses to oxygen deficiency.
Eating, exercise, and “thrifty” genotypes: connecting the dots toward an evolutionary understanding of modern chronic diseases
Authors: Chakravarthy Manu V. , Booth Frank W.
Published: January 2004

Survival of Homo sapiens during evolution was dependent on the procurement of food, which in turn was dependent on physical activity. However, food supply was never consistent. Thus it is contended that the ancient hunter-gatherer had cycles of feast and famine, punctuated with obligate periods of physical activity and rest. Hence, gene selection in the Late-Paleolithic era was probably influenced by physical activity and rest. To ensure survival during periods of famine, certain genes evolved to regulate efficient intake and utilization of fuel stores. Such genes were termed “thrifty genes” in 1962. Furthermore, convincing evidence shows that this ancient genome has remained essentially unchanged over the past 10,000 years and certainly not changed in the past 40-100 years. Although the absolute caloric intake of modern-day humans is likely lower compared with our hunter-gatherer ancestors, it is nevertheless in positive caloric balance in the majority of the US adult population mainly due to the increased sedentary lifestyle in present society. We contend that the combination of continuous food abundance and physical inactivity eliminates the evolutionarily programmed biochemical cycles emanating from feast-famine and physical activity-rest cycles, which in turn abrogates the cycling of certain metabolic processes, ultimately resulting in metabolic derangements such as obesity and Type 2 diabetes. In this context, we postulate that perhaps a crucial mechanism to break the stall of the metabolic processes would be via exercise through the regulation of “physical activity genes,” some of which may also be potential candidates for the “thrifty genes” of our hunter-gatherer ancestors. Therefore, the identification of such “thrifty gene” candidates would help provide insight into the pathogenetic processes of the numerous physical inactivity-mediated disorders.
Determinants of diaphragm motion in unilateral diaphragmatic paralysis
Authors: Scillia Pierre , Cappello Matteo , De Troyer André
Published: January 2004

Cranial displacement of a hemidiaphragm during sniffs is a cardinal sign of unilateral diaphragmatic paralysis in clinical practice. However, we have recently observed that isolated stimulation of one phrenic nerve in dogs causes the contralateral (inactive) hemidiaphragm to move caudally. In the present study, therefore, we tested the idea that, in unilateral diaphragmatic paralysis, the pattern of inspiratory muscle contraction plays a major role in determining the motion of the inactive hemidiaphragm. We induced a hemidiaphragmatic paralysis in six anesthetized dogs and assessed the contour of the diaphragm during isolated unilateral phrenic nerve stimulation and during spontaneous inspiratory efforts. Whereas the inactive hemidiaphragm moved caudally in the first instance, it moved cranially in the second. The parasternal intercostal muscles were then severed to reduce the contribution of the rib cage muscles to inspiratory efforts and to enhance the force generated by the intact hemidiaphragm. Although the change in pleural pressure (ΔPpl) was unaltered, the cranial displacement of the paralyzed hemidiaphragm was consistently reduced. A pneumothorax was finally induced to eliminate ΔPpl during unilateral phrenic nerve stimulation, and this enhanced the caudal displacement of the inactive hemidiaphragm. These observations indicate that, in unilateral diaphragmatic paralysis, the motion of the inactive hemidiaphragm is largely determined by the balance between the force related to ΔPpl and the force generated by the intact hemidiaphragm.
PGC-1α mRNA expression is influenced by metabolic perturbation in exercising human skeletal muscle
Authors: Norrbom Jessica , Sundberg Carl Johan , Ameln Helene , Kraus William E. , Jansson Eva , Gustafsson Thomas
Published: January 2004

Endurance training leads to many adaptational changes in several tissues. In skeletal muscle, fatty acid usage is enhanced and mitochondrial content is increased. The exact molecular mechanisms regulating these functional and structural changes remain to be elucidated. Contractile activity-induced metabolic perturbation has repeatedly been shown to be important for the induction of mitochondrial biogenesis. Recent reports suggest that the peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α)/mitochondrial transcription factor A (Tfam) pathway is involved in exercise-induced mitochondrial biogenesis. In the present study, nine healthy men performed two 45-min bouts of one-legged knee extension exercise: one bout with restricted blood flow, and the other with nonrestricted blood flow to the working muscle. Muscle biopsies were obtained from the vastus lateralis muscle before exercise and at 0, 30, 120, and 360 min after the exercise bout. Biopsies were analyzed for whole muscle, as well as fiber-type specific mRNA expression of myocyte-enriched calcineurin interacting protein (MCIP)-1, PGC-1α, and downstream mitochondrial transcription factors. A novel finding was that, in human skeletal muscle, PGC-1α mRNA increased more after exercise with restricted blood flow than in the nonrestricted condition. No changes were observed for the mRNA of NRF-1, Tfam, mitochondrial transcription factor B1, and mitochondrial transcription factor B2. Muscle fiber type I and type II did not differ in the basal PGC-1α mRNA levels or in the expression increase after ischemic training. Another novel finding was that there was no difference between the restricted and nonrestricted exercise conditions in the increase of MCIP-1 mRNA, a marker for calcineurin activation. This suggests that calcineurin may be activated by exercise in humans and does not exclude that calcineurin could play a role in PGC-1 transcription activation in human skeletal muscle.
Immediate exercise hyperemia in humans is contraction intensity dependent: evidence for rapid vasodilation
Authors: Tschakovsky M. E. , Rogers A. M. , Pyke K. E. , Saunders N. R. , Glenn N. , Lee S. J. , Weissgerber T. , Dwyer E. M.
Published: January 2004

We tested the hypothesis that rapid vasodilation proportional to contraction intensity contributes to the immediate (first cardiac cycle after initial contraction) exercise hyperemia. Ten healthy subjects performed single 1-s isometric forearm contractions at 5, 10, 15, 20, 30, 50, and 70% maximal voluntary contraction intensity (MVC) in arm above heart (AH) and below heart (BH) positions. Forearm blood flow (FBF; brachial artery mean blood velocity, Doppler ultrasound), mean arterial pressure (arterial tonometry), and heart rate (electrocardiogram) were measured beat by beat. Venous emptying (measured with a forearm strain gauge) was already maximized at 5% MVC, indicating that increases in contraction intensity did not further empty the forearm veins. Immediate increases in FBF were linearly proportional to contraction intensity from 5 to 70% MVC in AH (slope = 4.4 ± 0.5%ΔFBF/%MVC). In BH, the immediate increase in FBF demonstrated a curvilinear relationship with increasing contraction intensity and was greater than AH at 15, 20, 30, and 50% MVC ( P < 0.05). Peak changes in FBF were greater in BH vs. AH from 10 to 50% MVC, even when venous refilling was complete ( P < 0.05). These data support the existence of a rapid-acting vasodilatory mechanism(s) at the onset of human forearm exercise.
Keratinocyte growth factor transiently alters pulmonary function in rats
Authors: Hohlfeld Jens M. , Hoymann Heinz G. , Tschernig Thomas , Fehrenbach Antonia , Krug Norbert , Fehrenbach Heinz
Published: January 2004

Keratinocyte growth factor (KGF) is a mitogen for pulmonary epithelial cells. Intratracheal administration of KGF to adult rats results in alveolar epithelial type II and bronchiolar epithelial cell proliferation. While cellular responses to KGF have been intensively studied, functional consequences regarding lung function are unknown. Therefore, in this study, we sought to investigate whether KGF alters pulmonary function variables. Rats received either recombinant human KGF (rHuKGF) (5 mg/kg) or vehicle intratracheally. Before and on days 3 and 7 after treatment, pulmonary function was determined by body plethysmography. Subsequently, lung histological changes were quantified. rHuKGF induced a transient proliferation of alveolar and bronchiolar epithelial cells. The extent of type II cell hyperplasia was significantly correlated with a transient reduction in tidal volume and an increase in breathing frequency. In addition, quasi-static compliance, total lung capacity, and vital capacity were reduced after rHuKGF instillation, suggesting the development of a transitory restrictive lung disorder. Moreover, reduced expiratory flow rates and forced expiratory volumes, as well as increased functional residual capacity after rHuKGF but not vehicle, suggest obstructive lung function changes. In conclusion, the induction of alveolar and bronchiolar epithelial cell proliferation by KGF is paralleled by moderate functional consequences that should be taken into account when the therapeutic potential of KGF is tested.
Enhanced survival effect of pyruvate correlates MAPK and NF-κB activation in hydrogen peroxide-treated human endothelial cells
Authors: Lee Yong-Jin , Kang Il-Jun , Bünger Rolf , Kang Young-Hee
Published: January 2004

We recently reported that pyruvate inhibited translocation and activation of p53 caused by DNA damage due to oxidant injury (Lee YJ, Kang IJ, Bünger R, and Kang YH. Microvasc Res 66: 91-101, 2003); this was associated with increased expression of apoptosis-related bcl-2 and decreased expression of bax gene. This study attempted to delineate possible regulatory sites and mechanisms of antiapoptotic pyruvate, focusing on reactive oxygen species-mediated signaling in a human umbilical vein endothelial cell model. We compared the effects of the cytosolic reductant l-lactate and malate-aspartate shuttle blocker aminooxyacetate, both of which increase cytosolic NADH, on the downstream signaling pathway. Hydrogen peroxide (0.5 mM H2O2) depleted intracellular total glutathione that was prevented by pyruvate but not by l-lactate or aminooxyacetate. Activation of caspase-3 and the cleavage of procaspase-6 and procaspase-7 were strongly inhibited by pyruvate but markedly enhanced by l-lactate and aminooxyacetate, implicating redox-related antiapoptotic mechanisms of pyruvate. Western blot analysis and immunochemical data revealed that H2O2-induced transactivation of nuclear factor-κB (NF-κB) was also inhibited by pyruvate but not by l-lactate or aminooxyacetate. In addition, H2O2downregulated extracellular signal-regulated kinase (ERK1/2) and phosphorylated p38 mitogen-activated protein kinase (MAPK), effects that were fully reversed by pyruvate within 2 h. Collectively, these findings indicate that pyruvate can protect cellular glutathione, thus enhancing cellular antioxidant potential, and that enhanced antioxidant potential can desensitize NF-κB transactivation due to reactive oxygen species, suggesting possible metabolic redox relations to NF-κB. Furthermore, pyruvate blocked the p38 MAPK pathway and activated the ERK pathway in an apparently redox-sensitive manner, which may regulate expression of genes believed to prevent apoptosis and promote cell survival. Thus pyruvate may have therapeutic potential for reducing endothelial dysfunction and improving survival during oxidative stress.
Intermittent hypoxia induces transient arousal delay in newborn mice
Authors: Durand E. , Lofaso F. , Dauger S. , Vardon G. , Gaultier C. , Gallego J.
Published: February 2004

Previous studies suggested that defective arousal might be a major mechanism in sleep-disordered breathing such as sudden infant death syndrome and obstructive sleep apnea. In this study, we examined the effects of intermittent hypoxia (IH) on the arousal response to hypoxia in 4-day-old mice. We hypothesized that IH would increase arousal latency, as previously reported in other species, and we measured the concomitant changes in ventilation to shed light on the relationship between breathing and arousal. Arousal was scored according to behavioral criteria. Breathing variables were measured noninvasively by use of whole-body flow plethysmography. In the hypoxic group ( n = 14), the pups were exposed to 5% O2 in N2 for 3 min and returned to air for 6 min. This test was repeated eight times. The normoxic mice ( n = 14) were constantly exposed to normoxia. The hypoxic mice showed a 60% increase in arousal latency ( P < 0.0001). Normoxic controls showed virtually no arousals. IH depressed normoxic ventilation below baseline prehypoxic levels, while preserving the ventilatory response to hypoxia. The breathing pattern and arousal responses recovered fully after 2 h of normoxia. We conclude that IH rapidly and reversibly depressed breathing and delayed arousal in newborn mice. Both effects may be due to hypoxia-induced release of inhibitory neurotransmitters acting concomitantly on both functions.
Peripheral chemoreceptors in health and disease
Authors: Prabhakar Nanduri R. , Peng Ying-Jie
Published: January 2004

Peripheral chemoreceptors (carotid and aortic bodies) detect changes in arterial blood oxygen and initiate reflexes that are important for maintaining homeostasis during hypoxemia. This mini-review summarizes the importance of peripheral chemoreceptor reflexes in various physiological and pathophysiological conditions. Carotid bodies are important for eliciting hypoxic ventilatory stimulation in humans and in experimental animals. In the absence of carotid bodies, compensatory upregulation of aortic bodies as well as other chemoreceptors contributes to the hypoxic ventilatory response. Peripheral chemoreceptors are critical for ventilatory acclimatization at high altitude. They also contribute in part to the exercise-induced hyperventilation, especially with submaximal and heavy exercise. During pregnancy, hypoxic ventilatory sensitivity increases, perhaps due to the actions of estrogen and progesterone on chemoreceptors. Augmented peripheral chemoreceptors have been implicated in early stages of recurrent apneas, congestive heart failure, and certain forms of hypertension. It is likely that chemoreceptors tend to maintain oxygen homeostasis and act as a defense mechanism to prevent the progression of the morbidity associated with these diseases. Experimental models of recurrent apneas, congestive heart failure, and hypertension offer excellent opportunities to unravel the cellular mechanisms associated with altered chemoreceptor function.
Decrease in heart rates by artificial CO2 hot spring bathing is inhibited by β1-adrenoceptor blockade in anesthetized rats
Authors: Hashimoto Masaaki , Yamamoto Noriyuki
Published: January 2004

To investigate the effects of carbon dioxide (CO2) hot spring baths on physiological functions, head-out immersion of urethane-anesthetized, fursheared male Wistar rats was performed. Animals were immersed in water (30 or 35°C) with high-CO2 content (∼1,000 parts/million; CO2-water). CO2-water for bathing was made by using an artificial spa maker with normal tap water and high-pressure CO2 from a gas cylinder. When a human foot was immersed for 10 min in the CO2-water at 35°C, the immersed skin reddened, whereas skin color did not change in normal tap water at the same temperature. Arterial blood pressure, heart rate (HR), underwater skin tissue blood flow, and temperatures of the colon and immersed skin were continuously measured while animals were immersed in a bathtub of water for ∼30 min at room temperature (26°C). Immersed skin vascular resistance, computed from blood pressure and tissue blood flow, was significantly lower in the CO2-water bath than in tap water at 30°C, but no differences were apparent at 35°C. HR of rats in CO2-water was significantly slower than in tap water at 35°C. Decreased HR in CO2-water was inhibited by infusion of atenolol (β1-adrenoceptor blocker), but it was unaffected by atropine (muscarinic cholinoceptor blocker). Theses results suggest that bradycardia in CO2 hot spring bathing is caused by inhibition of the cardiac sympathetic innervation. This CO2-water maker should prove a useful device for acquiring physiological evidence of balneotherapy.