bluuebunny/crossref_metadata_2025 huggingface dataset:
Decrease of O2deficit is a potential factor in increased time to exhaustion after specific endurance training
Authors: Demarle Alexandre P. , Slawinski Jean J. , Laffite Laurent P. , Bocquet Valery G. , Koralsztein Jean P. , Billat Veronique L.
Published: December 2017

The main purpose of this study was to investigate the effects of an 8-wk severe interval training program on the parameters of oxygen uptake kinetics, such as the oxygen deficit and the slow component, and their potential consequences on the time until exhaustion in a severe run performed at the same absolute velocity before and after training. Six endurance-trained runners performed, on a 400-m synthetic track, an incremental test and an all-out test, at 93% of the velocity at maximal oxygen consumption, to assess the time until exhaustion. These tests were carried out before and after 8 wk of a severe interval training program, which was composed of two sessions of interval training at 93% of the velocity at maximal oxygen consumption and three recovery sessions of continuous training at 60–70% of the velocity at maximal oxygen consumption per week. Neither the oxygen deficit nor the slow component were correlated with the time until exhaustion ( r = −0.300, P = 0.24, n = 18 vs. r = −0.420, P = 0.09, n = 18, respectively). After training, the oxygen deficit significantly decreased ( P= 0.02), and the slow component did not change ( P = 0.44). Only three subjects greatly improved their time until exhaustion (by 10, 24, and 101%). The changes of oxygen deficit were significantly correlated with the changes of time until exhaustion ( r = −0.911, P = 0.01, n = 6). It was concluded that the decrease of oxygen deficit was a potential factor for the increase of time until exhaustion in a severe run performed after a specific endurance-training program.
Habituation of thermal sensations, skin temperatures, and norepinephrine in men exposed to cold air
Authors: Leppäluoto J. , Korhonen I. , Hassi J.
Published: December 2017

We studied habituation processes by exposing six healthy men to cold air (2 h in a 10°C room) daily for 11 days. During the repeated cold exposures, the general cold sensations and those of hand and foot became habituated so that they were already significantly less intense after the first exposure and remained habituated to the end of the experiment. The decreases in skin temperatures and increases in systolic blood pressure became habituated after four to six exposures, but their habituations occurred only at a few time points during the 120-min cold exposure and vanished by the end of the exposures. Serum thyroid-stimulating hormone, total thyroxine and triiodothyronine, norepinephrine, epinephrine, cortisol, and total proteins were measured before and after the 120-min cold exposure on days 0, 5, and 10. The increase in norepinephrine response became reduced on days 5 and 10 and that of proteins on day 10, suggesting that the sympathetic nervous system became habituated and hemoconcentration became attenuated. Thus repeated cold-air exposures lead to habituations of cold sensation and norepinephrine response and to attenuation of hemoconcentration, which provide certain benefits to those humans who have to stay and work in cold environments.
Angiogenin gene-race interaction for resting and exercise BP phenotypes: the HERITAGE Family Study
Authors: Rivera Miguel A. , Echegaray Marcos , Rankinen Tuomo , Pérusse Louis , Rice Treva , Gagnon Jacques , Leon Arthur S. , Skinner James S. , Wilmore Jack H. , Rao D. C. , Bouchard Claude
Published: December 2017

We examined the association between an angiogenin gene polymorphism and blood pressure (BP) at rest and in response to acute exercise before and after a 20-wk endurance-training program. Subjects were 737 normotensive and borderline hypertensive subjects (257 black and 480 white). The polymorphism was detected by PCR and digestion with AvaII, yielding an allele of 253 bp or a rare allele of 194 + 59 bp. Resting and exercise [50 W; 60, 80, and 100% of maximal O2consumption (V˙o2 max)] systolic (SBP) and diastolic BP were determined before and after training. Among blacks, adjusted SBP in the sedentary state was significantly lower in carriers of the rare allele at rest and exercise intensities of 60, 80, and 100% ofV˙o2 max. In the trained state, carriers of the rare allele had a significantly ( P < 0.05) lower SBP than did noncarriers at rest and at 80 and 100% ofV˙o2 max. The genotypic effect observed among blacks was not evident among whites. Furthermore, change in BP (after − before) was not significantly associated with the genotype. In conclusion, the angiogenin gene AvaII polymorphism is associated with a lower SBP at rest and in response to acute high-intensity exercise in blacks but not in whites.
Effect of exercise and medium-chain fatty acids on postprandial lipemia
Authors: Thomas Tom R. , Horner Kristen E. , Langdon Melissa M. , Zhang John Q. , Krul Elaine S. , Sun Grace Y. , Cox Richard H.
Published: December 2017

The purpose of this study was to evaluate the effect of medium-chain triglycerides (MCT) with and without exercise on postprandial lipemia (PPL). Subjects were 25 young men and women. Each subject performed three trials: 1) control (fat meal only, 1.5 g fat/kg) 2) MCT (substitution of MCT oil, 30% of fat calories), and 3) MCT + Ex (exercise 12 h before the MCT meal). Before each trial, the subject underwent consistent dietary preparation. Blood was collected on 2 separate days for baseline measurements of postheparin lipases and, in each trial, at 0 h (premeal), at 2, 4, 6, and 8 h after the fat meal for triglycerides and cholesterol ester transfer protein (CETP), and at 8 h for postheparin lipoprotein lipase (LPL) and hepatic lipase activities (HL). ANOVA indicated that the partial substitution of MCT oil to the fat meal did not affect the PPL response. However, the PPL was significantly lower after the MCT + Ex trial vs. the other trials. LPL activity was significantly elevated after all trials compared with baseline, whereas HL was lower in the MCT + Ex trial only. CETP mass was significantly lower at 4 and 8 h than 0 h during all trials but relatively higher in the MCT + Ex trial vs. the nonexercise trials. These results suggest that MCT does not affect the TG response to a fat meal. LPL and CETP are affected by a fat meal with or without exercise, but HL is affected only when exercise is included.
Regional differences in intramyocellular lipids in humans observed by in vivo 1H-MR spectroscopic imaging
Authors: Hwang Jong-Hee , Pan Jullie W. , Heydari S. , Hetherington Hoby P. , Stein Daniel T.
Published: December 2017

Regional differences in the content of intramyocellular lipids (IMCL), extramyocellular lipids, and total creatine (TCr) were quantified in soleus (S), tibialis posterior (TP), and tibialis anterior (TA) muscles in humans using in vivo 1H proton spectroscopic imaging at 4 T. Improved spatial resolution (0.25-ml nominal voxel resolution) made it feasible to measure IMCL in S, TP, and TA simultaneously in vivo. The most significant regional difference was found in the content of IMCL compared with extramyocellular lipids or TCr. The concentrations of TCr were found to be 29–32 mmol/kg, with little regional variation. IMCL content was measured to be 4.8 ± 1.6 mmol/kg tissue wt in S, 2.8 ± 1.3 mmol/kg tissue wt in TP, and 1.6 ± 0.9 mmol/kg tissue wt in TA in the order of S > TP > TA ( P < 0.05). It is likely that these IMCL values are consistent with the known fiber types of these muscles, with S having the greatest fraction of type I (slow-twitch, oxidative) fibers and TA having a large fraction of type IIb (fast-twitch, glycolytic) fibers.
Generation of oxidative stress contributes to the development of pulmonary hypertension induced by hypoxia
Authors: Hoshikawa Yasushi , Ono Sadafumi , Suzuki Satoshi , Tanita Tatsuo , Chida Masayuki , Song Chun , Noda Masafumi , Tabata Toshiharu , Voelkel Norbert F. , Fujimura Shigefumi
Published: December 2017

Chronic hypoxia causes pulmonary hypertension and right ventricular hypertrophy associated with pulmonary vascular remodeling. Because hypoxia might promote generation of oxidative stress in vivo, we hypothesized that oxidative stress may play a role in the hypoxia-induced cardiopulmonary changes and examined the effect of treatment with the antioxidant N-acetylcysteine (NAC) in rats. NAC reduced hypoxia-induced cardiopulmonary alterations at 3 wk of hypoxia. Lung phosphatidylcholine hydroperoxide (PCOOH) increased at days 1 and 7 of the hypoxic exposure, and NAC attenuated the increase in lung PCOOH. Lung xanthine oxidase (XO) activity was elevated from day 1 through day 21, especially during the initial 3 days of the hypoxic exposure. The XO inhibitor allopurinol significantly inhibited the hypoxia-induced increase in lung PCOOH and pulmonary hypertension, and allopurinol treatment only for the initial 3 days also reduced the hypoxia-induced right ventricular hypertrophy and pulmonary vascular thickening. These results suggest that oxidative stress produced by activated XO in the induction phase of hypoxic exposure contributes to the development of chronic hypoxic pulmonary hypertension.
Pulmonary perfusion in supine and prone positions: an electron-beam computed tomography study
Authors: Jones Andrew T. , Hansell David M. , Evans Timothy W.
Published: December 2017

Acute respiratory distress syndrome is characterized by alterations in the ventilation-perfusion ratio. Present techniques for studying regional pulmonary perfusion are difficult to apply in the critically ill. Electron-beam computed tomography was used to study the effects of prone positioning on regional pulmonary perfusion in six healthy subjects. Contrast-enhanced sections were obtained sequentially in the supine, prone, and (original) supine positions at full inspiration. Regions of interest were placed along the nondependent to dependent axis and relative perfusion calculated. When corrected for the redistribution of lung parenchyma, a gravitational gradient of pulmonary perfusion existed in both supine and prone positions. The distribution of perfusion between the supine or prone positions did not differ, but data analysis using smaller regions of interest demonstrated marked heterogeneity of perfusion between anatomically adjacent regions of lung. The distribution of lung parenchyma was more uniform in the prone position. Gravity was estimated to be responsible for 22–34% of perfusion heterogeneity in the supine and 27–41% in the prone positions. These data support the hypothesis that factors other than gravity may be at least as important in determining the distribution of pulmonary perfusion in humans. The influence of nongravitational factors may not be detectable if techniques that sample large tissue volumes are employed.
Behavior of fascicles and tendinous structures of human gastrocnemius during vertical jumping
Authors: Kurokawa Sadao , Fukunaga Tetsuo , Fukashiro Senshi
Published: December 2017

Behavior of fascicles and tendinous structures of human gastrocnemius medialis (MG) was determined by use of ultrasonography in vivo during jumping. Eight male subjects jumped vertically without countermovement (squat jump, SQJ). Simultaneously, kinematics, kinetics, and electromyography from lower leg muscles were recorded during SQJ. During phase I (−350 to −100 ms before toe-off), muscle-tendon complex (MTC) length was almost constant. Fascicles, however, shortened by 26%, and tendinous structures were stretched by 6%, storing elastic energy of 4.9 J during phase I. During phase II (−100 ms to toe-off), although fascicles generated force quasi-isometrically, MTC shortened rapidly by 5.3%, releasing prestored elastic energy with a higher peak positive power than that of fascicles. Also, the compliance of tendinous structures in vivo was somewhat higher than that of external tendon used in the simulation studies. The results demonstrate that the compliance of tendinous structures, together with no yielding of muscle fibers, allows MTC to effectively generate relatively large power at a high joint angular velocity region during the last part of push-off.
Mechanical compression influences intracellular Ca2+signaling in chondrocytes seeded in agarose constructs
Authors: Roberts Susan R. , Knight Martin M. , Lee David A. , Bader Dan L.
Published: December 2017

Ca2+signaling forms part of a possible mechanotransduction pathway by which chondrocytes may alter their metabolism in response to mechanical loading. In this study, a well-characterized model system utilizing bovine articular chondrocytes embedded in 4% agarose constructs was used to investigate the effect of physiological mechanical compressive strain applied after 1 and 3 days in culture. The intracellular Ca2+concentration was measured by use of the ratiometric Ca2+indicator indo 1-AM and confocal microscopy. A positive Ca2+response was defined as a percent increase in Ca2+ratio above a preset threshold. A significantly greater percentage of cells exhibited a positive Ca2+response in strained constructs compared with unstrained controls at both time points. In strained constructs, treatment with either Ga3+or EGTA significantly reduced the number of positive Ca2+responders compared with untreated controls. These results represent an important step in understanding the physiological role of intracellular Ca2+in chondrocytes under mechanical compression.
Contribution of amiloride-insensitive pathways to alveolar fluid clearance in adult rats
Authors: Norlin Andreas , Lu Le Nha , Guggino Sandra E. , Matthay Michael A. , Folkesson Hans G.
Published: December 2017

The contributions of amiloride-sensitive and -insensitive fractions of alveolar fluid clearance in adult ventilated rats were studied under control conditions and after β-adrenergic stimulation. Rats were instilled with a 5% albumin solution containing terbutaline (10−4M) or dibutyryl-cGMP (DBcGMP; 10−4M) with or without the cyclic nucleotide-gated cation channel inhibitor l- cis-diltiazem (10−3M) and/or amiloride (10−3M). Alveolar fluid clearance over 1 h was 18 ± 2% in controls. In controls, amiloride inhibited 46 ± 15% of alveolar fluid clearance, whereas l- cis-diltiazem had no inhibitory effect. Terbutaline and DBcGMP stimulated alveolar fluid clearance by 85 ± 3 and 36 ± 5%, respectively. Amiloride and l- cis-diltiazem inhibited nearly equal fractions of terbutaline-stimulated alveolar fluid clearance when given alone. Amiloride and l- cis-diltiazem given together inhibited a significantly larger fraction of alveolar fluid clearance in terbutaline-stimulated rats and in DBcGMP-stimulated rats. Based on these data, terbutaline stimulation recruited both amiloride-sensitive and l- cis-diltiazem-sensitive pathways. In contrast, DBcGMP mainly recruited l- cis-diltiazem-sensitive pathways. Therefore, the amiloride-insensitive fraction of Na+-driven alveolar fluid clearance may be partly mediated through cyclic nucleotide-gated cation channels and activated by an increase in intracellular cGMP.
Effect of load on preferred speed and cost of transport
Authors: Wickler S. J. , Hoyt D. F. , Cogger E. A. , Hall K. M.
Published: December 2017

Horses have a tendency to utilize a relatively narrow set of speeds near the middle of a much broader range they are capable of using within a particular gait, i.e., a preferred speed. Possible explanations for this behavior include minimizing musculoskeletal stresses and maximizing metabolic economy. If metabolic economy (cost of transport, CT) and preferred speeds are linked, then shifts in CTshould produce shifts in preferred speed. To test this hypothesis, preferred speed was measured in trotting horses ( n = 7) unloaded on the level and loaded with 19% of their body weight on the level. The preferred speed on the level was 3.33 ± 0.09 (SE) m/s, and this decreased to 3.13 ± 0.11 m/s when loaded. In both conditions (no load and load), the rate of O2consumption ( n = 3) was a curvilinear function of speed that produced a minimum CT(i.e., speed at which trotting is most economical). When unloaded, the speed at which CTwas minimum was very near the preferred speed. With a load, CTdecreased and the minimum was also near the preferred speed of horses while carrying a load.
Central GABAergic mechanisms are involved in apnea induced by SLN stimulation in piglets
Authors: Abu-Shaweesh Jalal M. , Dreshaj Ismail A. , Haxhiu Musa A. , Martin Richard J.
Published: December 2017

Stimulation of the superior laryngeal nerve (SLN) results in apnea in animals of different species, the mechanism of which is not known. We studied the effect of the GABAAreceptor blocker bicuculline, given intravenously and intracisternally, on apnea induced by SLN stimulation. Eighteen 5- to 10-day-old piglets were studied: bicuculline was administered intravenously to nine animals and intracisternally to nine animals. The animals were anesthetized and then decerebrated, vagotomized, ventilated, and paralyzed. The phrenic nerve responses to four levels of electrical SLN stimulation were measured before and after bicuculline. SLN stimulation caused a significant decrease in phrenic nerve amplitude, phrenic nerve frequency, minute phrenic activity, and inspiratory time ( P < 0.01) that was proportional to the level of electrical stimulation. Increased levels of stimulation were more likely to induce apnea during stimulation that often persisted beyond cessation of the stimulus. Bicuculline, administered intravenously or intracisternally, decreased the SLN stimulation-induced decrease in phrenic nerve amplitude, minute phrenic activity, and phrenic nerve frequency ( P < 0.05). Bicuculline also reduced SLN-induced apnea and duration of poststimulation apnea ( P < 0.05). We conclude that centrally mediated GABAergic pathways are involved in laryngeal stimulation-induced apnea.
Effects of morphine and naloxone on fetal heart rate and movement in the pig
Authors: Cohen S. , Parvizi N. , Mulder E. J. H. , Van Oord H. A. , Jonker F. H. , Van Der Weijden G. C. , Taverne M. A. M.
Published: December 2017

To test the hypothesis that an increasing opioid tonus is involved in decreases in fetal heart rate (FHR) and movement (FM) during late gestation, we studied the effects of intravenous bolus injections of morphine (1 mg) and naloxone (1 mg) on FHR and FM in the fetal pig. Twenty-one fetuses (1 per sow) were catheterized at 90–104 days of gestation (median 100 days). Recordings of FHR (electrocardiograph or Doppler-derived signals) and FM (ultrasonography) were made from 15 min before to 45 min after treatment. Morphine administration significantly decreased FHR, but it increased FHR variation and forelimb movements (LM). LM were clustered, and this stereotyped behavior has never before been observed in any mammalian fetus. Naloxone administration increased gross body movements and FHR without significant changes in FHR variation. It is concluded that FHR and motility are under opioidergic control in the pig fetus. Both morphine and naloxone induce hypermotility, suggesting that naloxone does not act as a pure opioid antagonist in the fetal pig.
Selected Contribution: Role of spleen emptying in prolonging apneas in humans
Authors: Schagatay Erika , Andersson Johan P. A. , Hallén Magnus , Pålsson Birger
Published: December 2017

This study addressed the interaction between short-term adaptation to apneas with face immersion and erythrocyte release from the spleen. Twenty healthy volunteers, including ten splenectomized subjects, participated. After prone rest, they performed five maximal-duration apneas with face immersion in 10°C water, with 2-min intervals. Cardiorespiratory parameters and venous blood samples were collected. In subjects with spleens, hematocrit and hemoglobin concentration increased by 6.4% and 3.3%, respectively, over the serial apneas and returned to baseline 10 min after the series. A delay of the physiological breaking point of apnea, by 30.5% (17 s), was seen only in this group. These parameters did not change in the splenectomized group. Plasma protein concentration, preapneic alveolar Pco2, inspired lung volume, and diving bradycardia remained unchanged throughout the series in both groups. Serial apneas thus triggered the hematological changes that have been previously observed after long apneic diving shifts; they were rapidly reversed and did not occur in splenectomized subjects. This suggests that splenic contraction occurs in humans as a part of the diving response and may prolong repeated apneas.
Large energetic adaptations of elderly muscle to resistance and endurance training
Authors: Jubrias Sharon A. , Esselman Peter C. , Price Lance B. , Cress M. Elaine , Conley Kevin E.
Published: December 2017

This study determined the cellular energetic and structural adaptations of elderly muscle to exercise training. Forty male and female subjects (69.2 ± 0.6 yr) were assigned to a control group or 6 mo of endurance (ET) or resistance training (RT). We used magnetic resonance spectroscopy and imaging to characterize energetic properties and size of the quadriceps femoris muscle. The phosphocreatine and pH changes during exercise yielded the muscle oxidative properties, glycolytic ATP synthesis, and contractile ATP demand. Muscle biopsies taken from the same site as the magnetic resonance measurements were used to determine myosin heavy chain isoforms, metabolite concentrations, and mitochondrial volume densities. The ET group showed changes in all energetic pathways: oxidative capacity (+31%), contractile ATP demand (−21%), and glycolytic ATP supply (−56%). The RT group had a large increase in oxidative capacity (57%). Only the RT group exhibited change in structural properties: a rise in mitochondrial volume density (31%) and muscle size (10%). These results demonstrate large energetic, but smaller structural, adaptations by elderly muscle with exercise training. The rise in oxidative properties with both ET and RT suggests that the aerobic pathway is particularly sensitive to exercise training in elderly muscle. Thus elderly muscle remains adaptable to chronic exercise, with large energetic changes accompanying both ET and RT.
Simulated microgravity, psychic stress, and immune cells in men: observations during 120-day 6° HDT
Authors: Choukèr A. , Thiel M. , Baranov V. , Meshkov D. , Kotov A. , Peter K. , Messmer K. , Christ F.
Published: December 2017

Because 6° head-down tilt (HDT) is an established method to mimic low gravity on earth, the aim of the present study was to determine the effects of 120-day HDT on psychic stress and peripheral blood immune cells in six healthy male volunteers. Psychological state was assessed by a current stress test, and cortisol was measured in saliva. During HDT, all volunteers developed psychic stress, and the diurnal rhythm of cortisol secretion was significantly altered. In addition, urine excretion of dopamine and norepinephrine increased. The innate part of the immune response was activated, as evidenced by the increase in the expression of β2-integrins on polymorphonuclear leukocytes and a rise in the number of circulating natural killer (NK) cell lymphocytes. The ratio of T-helper to T-cytotoxic and T-suppressor cells decreased, whereas no changes in T and B lymphocytes were observed. Plasma levels of interleukin-6 increased significantly and returned to basal levels after the end of the HDT period. Thus 6° HDT appears to be a valid model to induce psychic stress and neuroendocrine-related changes in the immune system, changes that might also be encountered by astronauts and cosmonauts during long-duration spaceflights.
Detergent inhibits 70–90% of responses to intravenous endotoxin in awake sheep
Authors: Staub Norman C. , Longworth Kim E. , Serikov Vladimir , Jerome E. Heidi , Elsasser Ted
Published: December 2017

Sheep have reactive pulmonary intravascular macrophages, which are essential for the marked pulmonary vascular response to infusions of small quantities of endotoxin. In another species with reactive pulmonary intravascular macrophages, horses, our laboratory found that an intravenous biosafe detergent, tyloxapol, inhibited some systemic and pulmonary responses to endotoxin (Longworth KE, Smith BL, Staub NC, Steffey EP, and Serikov V. Am J Vet Res 57: 1063–1066, 1996). We determined whether the same detergent would inhibit endotoxin responses in awake sheep. In 10 awake, instrumented sheep with chronic lung lymph fistulas, we did a control experiment by intravenously infusing 1 μg/kg Escherichia coli endotoxin. One week later, we gave 40 μmol/kg tyloxapol intravenously 1–4 h before infusing the same dose of endotoxin. In these paired studies, we compared pulmonary hemodynamics, lung lymph dynamics, body temperature, circulating leukocyte concentrations, and circulating tumor necrosis factor for 6 h. In all 10 sheep, tyloxapol blocked 80–90% of the pulmonary responses and 70–90% of the systemic responses. Tyloxapol is safe, inexpensive, easy to use, and effective immediately. It may be a clinically useful approach to contravening many of the effects of endotoxemia, in humans as well as animals.
Myosin thick filament lability induced by mechanical strain in airway smooth muscle
Authors: Kuo Kuo-Hsing , Wang Lu , Paré Peter D. , Ford Lincoln E. , Seow Chun Y.
Published: December 2017

Airway smooth muscle adapts to different lengths with functional changes that suggest plastic alterations in the filament lattice. To look for structural changes that might be associated with this plasticity, we studied the relationship between isometric force generation and myosin thick filament density in cell cross sections, measured by electron microscope, after length oscillations applied to the relaxed porcine trachealis muscle. Muscles were stimulated regularly for 12 s every 5 min. Between two stimulations, the muscles were submitted to repeated passive ±30% length changes. This caused tetanic force and thick-filament density to fall by 21 and 27%, respectively. However, in subsequent tetani, both force and filament density recovered to preoscillation levels. These findings indicate that thick filaments in airway smooth muscle are labile, depolymerization of the myosin filaments can be induced by mechanical strain, and repolymerization of the thick filaments underlies force recovery after the oscillation. This thick-filament lability would greatly facilitate plastic changes of lattice length and explain why airway smooth muscle is able to function over a large length range.
Osteoblasts respond to pulsatile fluid flow with short-term increases in PGE2 but no change in mineralization
Authors: Nauman E. A. , Satcher R. L. , Keaveny T. M. , Halloran B. P. , Bikle D. D.
Published: December 2017

Although there is no consensus as to the precise nature of the mechanostimulatory signals imparted to the bone cells during remodeling, it has been postulated that deformation-induced fluid flow plays a role in the mechanotransduction pathway. In vitro, osteoblasts respond to fluid shear stress with an increase in PGE2production; however, the long-term effects of fluid shear stress on cell proliferation and differentiation have not been examined. The goal of this study was to apply continuous pulsatile fluid shear stresses to osteoblasts and determine whether the initial production of PGE2 is associated with long-term biochemical changes. The acute response of bone cells to a pulsatile fluid shear stress (0.6 ± 0.5 Pa, 3.0 Hz) was characterized by a transient fourfold increase in PGE2 production. After 7 days of static culture (0 dyn/cm2) or low (0.06 ± 0.05 Pa, 0.3 Hz) or high (0.6 ± 0.5 Pa, 3.0 Hz) levels of pulsatile fluid shear stress, the bone cells responded with an 83% average increase in cell number, but no statistical difference ( P > 0.53) between the groups was observed. Alkaline phosphatase activity per cell decreased in the static cultures but not in the low- or high-flow groups. Mineralization was also unaffected by the different levels of applied shear stress. Our results indicate that short-term changes in PGE2 levels caused by pulsatile fluid flow are not associated with long-term changes in proliferation or mineralization of bone cells.
Function of human eccrine sweat glands during dynamic exercise and passive heat stress
Authors: Kondo Narihiko , Shibasaki Manabu , Aoki Ken , Koga Shunsaku , Inoue Yoshimitsu , Crandall Craig G.
Published: December 2017

The purpose of this study was to identify the pattern of change in the density of activated sweat glands (ASG) and sweat output per gland (SGO) during dynamic constant-workload exercise and passive heat stress. Eight male subjects (22.8 ± 0.9 yr) exercised at a constant workload (117.5 ± 4.8 W) and were also passively heated by lower-leg immersion into hot water of 42°C under an ambient temperature of 25°C and relative humidity of 50%. Esophageal temperature, mean skin temperature, sweating rate (SR), and heart rate were measured continuously during both trials. The number of ASG was determined every 4 min after the onset of sweating, whereas SGO was calculated by dividing SR by ASG. During both exercise and passive heating, SR increased abruptly during the first 8 min after onset of sweating, followed by a slower increase. Similarly for both protocols, the number of ASG increased rapidly during the first 8 min after the onset of sweating and then ceased to increase further ( P > 0.05). Conversely, SGO increased linearly throughout both perturbations. Our results suggest that changes in forearm sweating rate rely on both ASG and SGO during the initial period of exercise and passive heating, whereas further increases in SR are dependent on increases in SGO.
Induction of a fatigue-resistant phenotype in rabbit fast muscle by small daily amounts of stimulation
Authors: Lopez-Guajardo Ana , Sutherland Hazel , Jarvis Jonathan C. , Salmons Stanley
Published: December 2017

We have shown that fatigue resistance can be induced in rabbit tibialis anterior (TA) muscles without excessive power loss by continuous stimulation at low frequencies, such as 5 Hz, and that the same result is obtained by delivering a 10-Hz pattern in equal on/ offperiods. Here we ask whether the same phenotype could be produced with daily amounts of stimulation that would be more appropriate for clinical use. We stimulated rabbit TA muscles for 6 wk, alternating fixed 30-min on periods of stimulation at 10 Hz with off periods of different duration. All patterns transformed fast-glycolytic fibers into fast-oxidative fibers. The muscles had fatigue-resistant properties but retained a higher contractile speed and power production than muscles transformed completely to the slow-oxidative type. We conclude that in the rabbit as little as one 30-min period of stimulation in 24 h can result in a substantial increase in the resistance of the muscle to fatigue.
Invited Review: Oxygen sensing during intermittent hypoxia: cellular and molecular mechanisms
Authors: Prabhakar Nanduri R.
Published: December 2017

To the majority of the population, recurrent episodes of hypoxia are more likely encountered in life than sustained hypoxia. Until recently, much of the information on the long-term effects of intermittent hypoxia has come from studies on human subjects experiencing chronic recurrent apneas. Recent development of animal models of intermittent hypoxia and techniques for exposing cell cultures to alternating cycles of hypoxia have led to new information on the effects of episodic hypoxia on oxygen-sensing mechanisms in the carotid body chemoreceptors and regulation of gene expression. The purpose of this review is to highlight some recent studies on the effects of intermittent hypoxia on oxygen sensing at the carotid bodies and regulation of gene expression. In a rodent model, chronic intermittent hypoxia selectively enhances hypoxic sensitivity of the carotid body chemoreceptors. More interestingly, chronic intermittent hypoxia also induces a novel form of plasticity in the carotid body, leading to long-term facilitation in the sensory discharge. Studies on cell cultures reveal that intermittent hypoxia is more potent in activating activator protein-1 and hypoxia-inducible factor-1 transcription factors than sustained hypoxia. Moreover, some evidence suggests that intermittent hypoxia utilizes intracellular signaling pathways distinct from sustained hypoxia. Reactive oxygen species generated during the reoxygenation phase of intermittent hypoxia might play a key role in the effects of intermittent hypoxia on carotid body function and gene expression. Global gene profile analysis in cell cultures suggests that certain genes are selectively affected by intermittent hypoxia, some upregulated and some downregulated. It is suggested that, in intact animals, coordinated gene regulation of gene expression might be critical for eliciting phenotypic changes in the cardiorespiratory systems in response to intermittent hypoxia. It is hoped that future studies will unravel new mechanisms that are unique to intermittent hypoxia that may lead to a better understanding of the changes in the cardiorespiratory systems and new therapies for diseases associated with chronic recurrent episodes of hypoxia.
Selected Contribution: Altered vascular reactivity in arterioles of chronic intermittent hypoxic rats
Authors: Tahawi Ziad , Orolinova Natalia , Joshua Irving G. , Bader Michael , Fletcher Eugene C.
Published: December 2017

Recurrent episodic hypoxia (EH) is a feature of sleep apnea that may be responsible for some chronic cardiovascular sequelae such as systemic hypertension. Chronic EH (8 h/day for 35 days) causes elevation of diurnal resting (unstimulated) mean arterial blood pressure (MAP) in the rat. We used in vivo video microscopy to examine arteriolar reactivity in the cremaster muscle of male Sprague-Dawley rats subjected to 35 days of EH. Cremaster muscles of EH ( n= 6) and control ( n = 6) rats were exposed to varying doses of norepinephrine (NE) (10−10 to 10−5M), ACh (10−9 to 10−5 M), and endothelin-1 (10−12 to 10−8 M). In a separate experiment, EH ( n = 5) and control ( n = 6) rats were given one dose of a nitric oxide synthase (NOS) inhibitor N G-nitro-l-arginine methyl ester (l-NAME; 10−5 M). We also examined endothelial NOS mRNA from the kidneys of EH-stimulated and control (unstimulated) rats. Telemetry-monitored EH rats showed a 16-mmHg increase in MAP over 35 days, whereas control rats showed no change. The response to NE and endothelin-1 were similar for EH and control rats. ACh vasodilatation of arterioles in EH rats was significantly attenuated compared with that of controls. The degree of vasoconstriction in response to blockade of the nitric oxide system byl-NAME was significantly less (83% of baseline diameter with l-NAME) for arterioles of EH rats compared with that for controls (61% of baseline diameter), implying lower basal resting nitric oxide release in the EH rats. Whole kidney mRNA endothelial NOS levels were not different between groups. These data support the hypothesis that chronic elevation of blood pressure associated with EH involves increased peripheral resistance from decreased basal release or production of nitric oxide after 35 days of EH.
Novel mechanism of hypertension revealed by cell-specific targeting of human angiotensinogen in transgenic mice
Authors: DAVISSON ROBIN L. , DING YUEMING , STEC DAVID E. , CATTERALL JAMES F. , SIGMUND CURT D.
Published: December 2017

Davisson, Robin L., Yueming Ding, David E. Stec, James F. Catterall, and Curt D. Sigmund. Novel mechanism of hypertension revealed by cell-specific targeting of human angiotensinogen in transgenic mice. Physiol. Genomics 1: 3–9, 1999.—We tested the hypothesis that the tissue-specific intrarenal renin-angiotensin system (RAS) can participate in the regulation of blood pressure independently of its endocrine counterpart, by generating two transgenic models that differ in their tissue-specific expression of human angiotensinogen (AGT). Human AGT expression was driven by its endogenous promoter in the systemic model and by the kidney androgen-regulated protein promoter in the kidney-specific model. Using molecular, biochemical, and physiological measurements, we demonstrate that human AGT mRNA and protein are restricted to the kidney in the kidney-specific model. Plasma ANG II was elevated in the systemic model but not in the kidney-specific model. Nevertheless, blood pressure was markedly elevated in both the systemic and kidney-specific transgenic mice. Acute administration of the selective ANG II AT-1 receptor antagonist losartan lowered blood pressure in the systemic model but not in the kidney-specific model. These results provide evidence for the potential importance of the intrarenal RAS in blood pressure regulation by showing that expression of AGT specifically in the kidney leads to chronic hypertension independently of the endocrine RAS.
Differential response to dietary fat in large (LG/J) and small (SM/J) inbred mouse strains
Authors: CHEVERUD JAMES M. , PLETSCHER L. SUSAN , VAUGHN TY T. , MARSHALL BESS
Published: December 2017

Cheverud, James M., L. Susan Pletscher, Ty T. Vaughn, and Bess Marshall. Differential response to dietary fat in large (LG/J) and small (SM/J) inbred mouse strains. Physiol. Genomics 1: 33–39, 1999.—The “large” (LG/J) and “small” (SM/J) inbred mouse strains differ for a wide variety of traits related to body size and obesity. Ninety-three LG/J and SM/J mice were divided into two treatment categories and fed a moderately high-fat diet (21% kcal fat) or a low-fat diet (12% kcal fat) from weaning to necropsy. Strain differences in obesity-related traits and differential response to dietary fat increases were analyzed using ANOVA. LG/J animals grow faster from 3 to 10 wk, have longer tails, and have heavier body weight, liver weight, and fat pad weight than SM/J animals. SM/J animals grow faster after 10 wk of age and have higher fasting glucose levels than LG/J animals. SM/J mice were more responsive to increased dietary fat than LG/J mice for growth after 10 wk, necropsy weight, liver weight, fat pad weights, and fasting glucose levels (in males). The growth from 3 to 10 wk had a much greater response in the LG/J strain, whereas tail length had no response. This pattern of dietary response is similar to that expected under the “thrifty” phenotype hypothesis. Genes affecting strain differences and the differential response of the strains to dietary fat can be successfully mapped in the intercross of the LG/J and SM/J strains. This intercross provides an excellent multigenic model for the genetic basis of complex traits and diseases related to body size and obesity.
GIST: A web tool for collecting gene information
Authors: HALUSHKA MARC K. , MATHEWS DEBRA J. , BAILEY JEFFREY A. , CHAKRAVARTI ARAVINDA
Published: December 2017

Halushka, Marc K., Debra J. Mathews, Jeffrey A. Bailey, and Aravinda Chakravarti. GIST: A web tool for collecting gene information. Physiol. Genomics 1: 75–81, 1999.—As the human genome is sequenced and annotated, an important step in future genetic studies of complex traits and diseases will be the identification of relevant candidate genes. To enable such compilations, it would be useful to collate all necessary and available genetic information for each candidate gene. To this end, we have created a web tool ( http://genome.cwru.edu/gist/gist.html ) to allow the rapid cataloging of currently available genetic data. This tool, called GIST (or “Gene Information Search Tool”), allows an investigator to search the major genomic databases containing gene and marker information from a single query point. To prove the utility of GIST, a catalog of 150 hypertension candidate genes was created. This resource collates all available nucleotide and amino acid sequence data, expression data, chromosomal map location, and genetic marker interval for each gene, collected from on-line databases. These data can be used to guide genetic studies of hypertension.
Why FRET over genomics?
Authors: DE ANGELIS DINO A.
Published: December 2017

De Angelis, Dino A. Why FRET over genomics? Physiol. Genomics 1: 93–99, 1999.—Genetic information is being uncovered quickly and in vast amounts through the largely automated sequencing of genomes from all kinds of organisms. As this information becomes available, enormous challenges are emerging on three levels: first, functions will have to be assigned to individual gene products; second, factors that influence the expression level of these gene products will have to be identified; and third, allelic variants that act alone or in combination to give rise to complex traits will have to be characterized. Because of the sheer size of genomes, methods that can streamline or automate these processes are highly desirable. Fluorescence is an attractive readout for such high-throughput tasks because of the availability of equipment designed to detect light-emitting compounds with great speed and high capacity. The following is an overview of the achievements and potential of fluorescence resonance energy transfer (FRET) as applied in three areas of genomics: the identification of single-nucleotide polymorphisms, the detection of protein-protein interactions, and the genomewide analysis of regulatory sequences.
Inflammation influences vascular remodeling through AT2receptor expression and signaling
Authors: AKISHITA MASAHIRO , HORIUCHI MASATSUGU , YAMADA HIROYUKI , ZHANG LUNAN , SHIRAKAMI GOTARO , TAMURA KOUICHI , OUCHI YASUYOSHI , DZAU VICTOR J.
Published: December 2017

Akishita, Masahiro, Masatsugu Horiuchi, Hiroyuki Yamada, Lunan Zhang, Gotaro Shirakami, Kouichi Tamura, Yasuyoshi Ouchi, and Victor J. Dzau. Inflammation influences vascular remodeling through AT2receptor expression and signaling. Physiol. Genomics 2: 13–20, 2000.—The AT2receptor, which exerts growth inhibitory effects in cell culture, is present scantily in the adult vasculature but is reexpressed after vascular injury. To examine the in vivo role of this receptor in vascular diseases, we developed a mouse model of vascular remodeling and compared the responses in wild-type ( Agtr2+) and AT2receptor knockout ( Agtr2−) mice. Polyethylene cuff placement on the femoral artery led to the vascular expression of cytokines, the transcriptional factor interferon regulatory factor-1 (IRF-1), and both the AT1and AT2receptors. Although the expressions of IRF-1 and AT1receptor were induced to comparable levels in both the Agtr2+and Agtr2−mice, the neointimal lesion size and the smooth muscle cell proliferation were twice greater in the Agtr2−than in the Agtr2+mouse. Correlated with this difference, AT2receptor expression was induced predominantly in the smooth muscle cells of Agtr2+mouse. These results demonstrate that the AT2receptor plays an important role in nonocclusive inflammatory injury by mediating the effects of inflammation on vascular smooth muscle growth inhibition.
Assessment of cellular profile and lung function with repeated bronchoalveolar lavage in individual mice
Authors: WALTERS DIANNE M. , WILLS-KARP MARSHA , MITZNER WAYNE
Published: December 2017

Walters, Dianne M., Marsha Wills-Karp, and Wayne Mitzner. Assessment of cellular profile and lung function with repeated bronchoalveolar lavage in individual mice. Physiol. Genomics 2: 29–36, 2000.—In this study, we sought to develop procedures that would enable repeated bronchoalveolar lavage (BAL) in individual mice on multiple occasions. To achieve this objective, we first developed the procedures that would allow individual mice to survive a whole lung lavage, and then tested whether, on subsequent days, there was an effect of this initial BAL on the cell profile, lung permeability, and baseline respiratory function. Our results demonstrate that the repeated lavage procedure can be readily carried out in individual mice of different strains on multiple occasions. The lavage procedure itself results in immediate increases in respiratory system resistance and concomitant decreases in compliance, but these parameters return to prelavage values by the 2nd or 3rd day postlavage. Lavage also induces variable increases in inflammatory cells depending on the strain used. However, in all three strains examined here (A/J, BALB/c, and C3H/HeJ), inflammatory cell numbers returned to baseline values within 3 days after an initial lavage procedure. The ability to perform repeated BAL in individual mice should prove to be an extremely useful tool in a variety of functional genomic studies in the lung.
Reverse genetics in zebrafish
Authors: LEKVEN ARNE C. , HELDE KATHRYN ANN , THORPE CHRISTOPHER J. , ROOKE REBECCA , MOON RANDALL T.
Published: December 2017

Lekven, Arne C., Kathryn Ann Helde, Christopher J. Thorpe, Rebecca Rooke, and Randall T. Moon. Reverse genetics in zebrafish. Physiol Genomics 2: 37–48, 2000.—The zebrafish has become a popular model system for the study of vertebrate developmental biology because of its numerous strengths as a molecular genetic and embryological system. To determine the requirement for specific genes during embryogenesis, it is necessary to generate organisms carrying loss-of-function mutations. This can be accomplished in zebrafish through a reverse genetic approach. This review discusses the current techniques for generating mutations in known genes in zebrafish. These techniques include the generation of chromosomal deletions and the subsequent identification of complementation groups within deletions through noncomplementation assays. In addition, this review will discuss methods currently being evaluated that may improve the methods for finding mutations in a known sequence, including screening for randomly induced small deletions within genes and screening for randomly induced point mutations within specific genes.
Targeting of human eNOS promoter to the Hprt locus of mice leads to tissue-restricted transgene expression
Authors: GUILLOT PASCALE V. , LIU LIXIN , KUIVENHOVEN JAN ALBERT , GUAN JASON , ROSENBERG ROBERT D. , AIRD WILLIAM C.
Published: December 2017

Guillot, Pascale V., Lixin Liu, Jan Albert Kuivenhoven, Jason Guan, Robert D. Rosenberg, and William C. Aird. Targeting of human eNOS promoter to the Hprt locus of mice leads to tissue-restricted transgene expression. Physiol Genomics 2: 77–83, 2000.—Phenotypic heterogeneity of the endothelium arises from cell type-specific differences in gene expression. An understanding of the mechanisms that underlie differential gene expression would provide important insight into the molecular basis of vascular diversity. In standard transgenic assays, multiple copies of heterologous DNA cassettes are randomly integrated into the mouse genome, resulting in significant line-to-line variation in expression. To overcome these limitations, we have targeted a single copy of a transgene that contains 1,600 bp of the human endothelial nitric oxide synthase (eNOS) promoter coupled to the LacZ reporter gene to the X-linked hypoxanthine phosphoribosyltransferase ( Hprt) locus of mice by homologous recombination. The transgene was inserted in either of the orientations relative to that of the Hprt gene. In mice derived from multiple embryonic stem (ES) cell clones, the expression pattern was limited to a subset of endothelial cells, cardiomyocytes, and vascular smooth muscle cells. These findings suggest that Hprt locus targeting is a feasible tool for studying endothelial cell-restricted gene regulation.