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The European Respiratory Journal Apr 1995In addition to its emerging immunodulatory properties, theophylline is a bronchodilator and also decreases mean pulmonary arterial pressure in vivo. The mechanism of... (Review)
Review
In addition to its emerging immunodulatory properties, theophylline is a bronchodilator and also decreases mean pulmonary arterial pressure in vivo. The mechanism of action of this drug remains controversial; adenosine antagonism, phosphodiesterase (PDE) inhibition and other actions have been advanced to explain its effectiveness in asthma. Cyclic adenosine monophosphate (AMP) and cyclic guanosine monophosphate (GMP) are involved in the regulation of smooth muscle tone, and the breakdown of these nucleotides is catalysed by multiple PDE isoenzymes. The PDE isoenzymes present in human bronchus and pulmonary artery have been identified, and the pharmacological actions of inhibitors of these enzymes have been investigated. Human bronchus and pulmonary arteries are relaxed by theophylline and by selective inhibitors of PDE III, while PDE IV inhibitors also relax precontracted bronchus and PDE V/I inhibitors relax pulmonary artery. There appears to be some synergy between inhibitors of PDE III and PDE IV in relaxing bronchus, and a pronounced synergy between PDE III and PDE V inhibitors in relaxing pulmonary artery. In neither tissue does 8-phenyltheophylline, a xanthine exhibiting adenosine antagonism but not PDE inhibition, cause any significant relaxation, implying that theophylline does not exert its actions through adenosine antagonism. The close correspondence of theophylline concentrations inhibiting bronchus or pulmonary artery PDE and those causing relaxation points towards PDE inhibition as the major mechanism of action of theophylline in smooth muscle relaxation.
Topics: Animals; Bronchi; Bronchodilator Agents; Cyclic AMP; Cyclic GMP; Humans; Muscle, Smooth; Muscle, Smooth, Vascular; Parasympatholytics; Phosphodiesterase Inhibitors; Pulmonary Artery; Theophylline
PubMed: 7664866
DOI: No ID Found -
The Journal of Physiology Mar 2018Oxygen pressure gradients across the microvascular walls are essential for oxygen diffusion from blood to tissue cells. At any given flux, the magnitude of these...
KEY POINTS
Oxygen pressure gradients across the microvascular walls are essential for oxygen diffusion from blood to tissue cells. At any given flux, the magnitude of these transmural gradients is proportional to the local resistance. The greatest resistance to oxygen transport into skeletal muscle is considered to reside in the short distance between red blood cells and myocytes. Although crucial to oxygen transport, little is known about transmural pressure gradients within skeletal muscle during contractions. We evaluated oxygen pressures within both the skeletal muscle microvascular and interstitial spaces to determine transmural gradients during the rest-contraction transient in anaesthetized rats. The significant transmural gradient observed at rest was sustained during submaximal muscle contractions. Our findings support that the blood-myocyte interface provides substantial resistance to oxygen diffusion at rest and during contractions and suggest that modulations in microvascular haemodynamics and red blood cell distribution constitute primary mechanisms driving increased transmural oxygen flux with contractions.
ABSTRACT
Oxygen pressure (PO2) gradients across the blood-myocyte interface are required for diffusive O transport, thereby supporting oxidative metabolism. The greatest resistance to O flux into skeletal muscle is considered to reside between the erythrocyte surface and adjacent sarcolemma, although this has not been measured during contractions. We tested the hypothesis that O gradients between skeletal muscle microvascular (PO2 mv ) and interstitial (PO2 is ) spaces would be present at rest and maintained or increased during contractions. PO2 mv and PO2 is were determined via phosphorescence quenching (Oxyphor probes G2 and G4, respectively) in the exposed rat spinotrapezius during the rest-contraction transient (1 Hz, 6 V; n = 8). PO2 mv was higher than PO2 is in all instances from rest (34.9 ± 6.0 versus 15.7 ± 6.4) to contractions (28.4 ± 5.3 versus 10.6 ± 5.2 mmHg, respectively) such that the mean PO2 gradient throughout the transient was 16.9 ± 6.6 mmHg (P < 0.05 for all). No differences in the amplitude of PO2 fall with contractions were observed between the microvasculature and interstitium (10.9 ± 2.3 versus 9.0 ± 3.5 mmHg, respectively; P > 0.05). However, the speed of the PO2 is fall during contractions was slower than that of PO2 mv (time constant: 12.8 ± 4.7 versus 9.0 ± 5.1 s, respectively; P < 0.05). Consistent with our hypothesis, a significant transmural gradient was sustained (but not increased) from rest to contractions. This supports that the blood-myocyte interface is the site of a substantial PO2 gradient driving O diffusion during metabolic transients. Based on Fick's law, elevated O flux with contractions must thus rely primarily on modulations in effective diffusing capacity (mainly erythrocyte haemodynamics and distribution) as the PO2 gradient is not increased.
Topics: Animals; Male; Microvessels; Muscle Cells; Muscle Contraction; Muscle, Skeletal; Oxygen; Oxygen Consumption; Rats; Rats, Sprague-Dawley; Rest
PubMed: 29288568
DOI: 10.1113/JP275170 -
Folia Medica Cracoviensia Apr 2023Temporomandibular disorder (TMD) is a disease of multifactorial etiology and a complex of symptoms, related to disorders of the masticatory muscles, temporomandibular... (Review)
Review
Temporomandibular disorder (TMD) is a disease of multifactorial etiology and a complex of symptoms, related to disorders of the masticatory muscles, temporomandibular joints and the surrounding orofacial structures. One of the main problems in the course of TMD disorders is the systematic increase in the tension of the masticatory muscles (masseter muscles, temporalis and medial and lateral pterygoid muscles), what is the cause of many damages and the development of pathological conditions in the stomatognathic system. The article discusses the differences in the structure of the masticatory and skeletal muscles, as well as the different nature and isoforms of myosin, which determines the much faster generation of contraction in the masticatory muscles and consequently easier generation of excessive, harmful tensions in the masticatory muscles. The article describes the causes of increased tension in the masticatory muscles and methods of their relaxation used in the basic and supportive treatment of temporomandibular disorders. The use of occlusal splints, physiotherapeutic procedures and TMD treatment with botulinum toxin type A were characterized. A role of psychological support and the methods used for patients with TMD were emphasized.
Topics: Humans; Temporomandibular Joint Disorders; Masticatory Muscles; Masseter Muscle; Temporomandibular Joint; Occlusal Splints
PubMed: 37406276
DOI: 10.24425/fmc.2023.145429 -
Magnetic Resonance Imaging Nov 2023T2 relaxation times (T2 times) are different between resting and exercised muscles and between muscles of healthy subjects and subjects with muscle pathology. However,...
T2 relaxation times (T2 times) are different between resting and exercised muscles and between muscles of healthy subjects and subjects with muscle pathology. However, studies specifically focusing on neck muscles are lacking. Furthermore, normative neck muscle T2 times are not well defined and methodology used to analyse T2 times in neck muscles is not robust. We analysed T2 times in key neck muscles and explored factors affecting variability between muscles. 20 healthy subjects were recruited. Two circular regions of interest (ROIs) were drawn in two mutually exclusive regions within neck muscles on T2 weighted images and values averaged. ROI measurements were performed by a co-investigator, supervised by a neuro-radiologist. For the first ten subjects, measurements were done from C1-T1. For the remaining subjects, ROIs were drawn at two pre-determined levels. Two MRIs were repeated at 31 degrees acquisition to evaluate the effect of muscle fibre orientation. ROI values were translated into T2 times. Results showed semispinalis capitis had the longest T2 times (range 46.88-51.42 ms), followed by splenius capitis (range 47.37-48.33 ms), trapezius (range 45.27-47.46 ms), levator scapulae (range 43.17-45.63 ms) and sternocleidomastoid (range 38.45-42.91 ms). T2 times did not vary along length of muscles and were unaffected by muscle fibre orientation (P > 0.05). T2 times of splenius capitis correlated significantly with age at C2/C3 and C5/C6 levels and trapezius at C7/T1 level. Gender did not influence relaxation times (P > 0.05). In conclusion, results of normative neck muscle T2 time values and factors influencing the T2 times could serve as a reference for future MR analysis of neck muscles. The methodology used may also be useful for related studies of neck muscles.
Topics: Humans; Neck Muscles; Magnetic Resonance Imaging; Rest; Healthy Volunteers
PubMed: 37517766
DOI: 10.1016/j.mri.2023.07.013 -
Journal of Applied Physiology... Mar 2017
Topics: Cardiovascular System; Cumulative Trauma Disorders; Exercise; Fatigue; Hormones; Humans; Muscle, Skeletal; Rest
PubMed: 28153939
DOI: 10.1152/japplphysiol.00086.2017 -
The Journal of Physiology Nov 2018Insulin sensitivity (as determined by a hyperinsulinaemic-euglyceamic clamp) decreased 15% after reduced activity. Despite not fully returning to baseline physical... (Clinical Trial)
Clinical Trial
KEY POINTS
Insulin sensitivity (as determined by a hyperinsulinaemic-euglyceamic clamp) decreased 15% after reduced activity. Despite not fully returning to baseline physical activity levels, insulin sensitivity unexpectedly, rebounded above that recorded before 2 weeks of reduced physical activity by 14% after the recovery period. Changes in insulin sensitivity in response to reduced activity were primarily driven by men but, not women. There were modest changes in ceramides (nuclear/myofibrillar fraction and serum) following reduced activity and recovery but, in the absence of major changes to body composition (i.e. fat mass), ceramides were not related to changes in inactivity-induced insulin sensitivity in healthy older adults.
ABSTRACT
Older adults are at risk of physical inactivity as they encounter debilitating life events. It is not known how insulin sensitivity is affected by modest short-term physical inactivity and recovery in healthy older adults, nor how insulin sensitivity is related to changes in serum and muscle ceramide content. Healthy older adults (aged 64-82 years, five females, seven males) were assessed before (PRE), after 2 weeks of reduced physical activity (RA) and following 2 weeks of recovery (REC). Insulin sensitivity (hyperinsulinaemic-euglyceamic clamp), lean mass, muscle function, skeletal muscle subfraction, fibre-specific, and serum ceramide content and indices of skeletal muscle inflammation were assessed. Insulin sensitivity decreased by 15 ± 6% at RA (driven by men) but rebounded above PRE by 14 ± 5% at REC. Mid-plantar flexor muscle area and leg strength decreased with RA, although only muscle size returned to baseline levels following REC. Body fat did not change and only minimal changes in muscle inflammation were noted across the intervention. Serum and intramuscular ceramides (nuclear/myofibrillar fraction) were modestly increased at RA and REC. However, ceramides were not related to changes in inactivity-induced insulin sensitivity in healthy older adults. Short-term inactivity induced insulin resistance in older adults in the absence of significant changes in body composition (i.e. fat mass) are not related to changes in ceramides.
Topics: Aged; Aged, 80 and over; Aging; Ceramides; Exercise; Female; Humans; Insulin Resistance; Male; Middle Aged; Muscle, Skeletal; Recovery of Function; Rest
PubMed: 30194727
DOI: 10.1113/JP276798 -
Journal of Alzheimer's Disease : JAD 2010We review the electrophysiological studies concerning the effects of caffeine on muscle, lower and upper motor neuron excitability and cognition. Several different... (Review)
Review
We review the electrophysiological studies concerning the effects of caffeine on muscle, lower and upper motor neuron excitability and cognition. Several different methods have been used, such as electromyography, recruitment analysis, H-reflex, transcranial magnetic stimulation (TMS), electroencephalography and event-related potentials. The positive effect of caffeine on vigilance, attention, speed of reaction, information processing and arousal is supported by a number of electrophysiological studies. The evidence in favor of an increased muscle fiber resistance is not definitive, but higher or lower motor neuron excitability can occur as a consequence of a greater excitation of the descending input from the brainstem and upper motor neurons. TMS can address the influence of caffeine on the upper motor neuron. Previous studies showed that cortico-motor threshold and intracortical excitatory and inhibitory pathways are not influenced by caffeine. Nonetheless, our results indicate that cortical silent period (CSP) is reduced in resting muscles after caffeine consumption, when stimulating the motor cortex with intensities slightly above threshold. We present new data demonstrating that this effect is also observed in fatigued muscle. We conclude that CSP can be considered a surrogate marker of the effect of caffeine in the brain, in particular of its central ergogenic effect.
Topics: Adult; Analysis of Variance; Caffeine; Central Nervous System Stimulants; Electrophysiology; Evoked Potentials; Fatigue; Humans; Male; Motor Neurons; Muscles; Rest; Transcranial Magnetic Stimulation; Young Adult
PubMed: 20164574
DOI: 10.3233/JAD-2010-1377 -
The Journal of Biological Chemistry Mar 2022Muscle myosin heads, in the absence of actin, have been shown to exist in two states, the relaxed (turnover ∼0.05 s) and super-relaxed states (SRX, 0.005 s) using a...
Muscle myosin heads, in the absence of actin, have been shown to exist in two states, the relaxed (turnover ∼0.05 s) and super-relaxed states (SRX, 0.005 s) using a simple fluorescent ATP chase assay (Hooijman, P. et al (2011) Biophys. J.100, 1969-1976). Studies have normally used purified proteins, myosin filaments, or muscle fibers. Here we use muscle myofibrils, which retain most of the ancillary proteins and 3-D architecture of muscle and can be used with rapid mixing methods. Recording timescales from 0.1 to 1000 s provides a precise measure of the two populations of myosin heads present in relaxed myofibrils. We demonstrate that the population of SRX states is formed from rigor cross bridges within 0.2 s of relaxing with fluorescently labeled ATP, and the population of SRX states is relatively constant over the temperature range of 5 °C-30 °C. The SRX population is enhanced in the presence of mavacamten and reduced in the presence of deoxy-ATP. Compared with myofibrils from fast-twitch muscle, slow-twitch muscle, and cardiac muscles, myofibrils require a tenfold lower concentration of mavacamten to be effective, and mavacamten induced a larger increase in the population of the SRX state. Mavacamten is less effective, however, at stabilizing the SRX state at physiological temperatures than at 5 °C. These assays require small quantities of myofibrils, making them suitable for studies of model organism muscles, human biopsies, or human-derived iPSCs.
Topics: Adenosine Triphosphate; Humans; Muscle Fibers, Fast-Twitch; Muscle Fibers, Slow-Twitch; Muscle, Skeletal; Myocardium; Myofibrils; Myosins
PubMed: 35090895
DOI: 10.1016/j.jbc.2022.101640 -
Cell Reports Jun 2020To better understand the health benefits of lifelong exercise in humans, we conduct global skeletal muscle transcriptomic analyses of long-term endurance- (9 men, 9... (Comparative Study)
Comparative Study
To better understand the health benefits of lifelong exercise in humans, we conduct global skeletal muscle transcriptomic analyses of long-term endurance- (9 men, 9 women) and strength-trained (7 men) humans compared with age-matched untrained controls (7 men, 8 women). Transcriptomic analysis, Gene Ontology, and genome-scale metabolic modeling demonstrate changes in pathways related to the prevention of metabolic diseases, particularly with endurance training. Our data also show prominent sex differences between controls and that these differences are reduced with endurance training. Additionally, we compare our data with studies examining muscle gene expression before and after a months-long training period in individuals with metabolic diseases. This analysis reveals that training shifts gene expression in individuals with impaired metabolism to become more similar to our endurance-trained group. Overall, our data provide an extensive examination of the accumulated transcriptional changes that occur with decades-long training and identify important "exercise-responsive" genes that could attenuate metabolic disease.
Topics: Adult; Aerobiosis; Athletes; Biopsy; Female; Gene Ontology; Genome, Human; Humans; Male; Middle Aged; Muscle, Skeletal; Physical Endurance; Resistance Training; Rest; Sedentary Behavior; Sequence Analysis, RNA; Sex Characteristics; Transcriptome
PubMed: 32579934
DOI: 10.1016/j.celrep.2020.107808 -
Journal of Anatomy Aug 2008The symmetry of, and physical characteristics influencing, the thickness of the lateral abdominal muscles at rest and during abdominal exercises were examined in 57...
The symmetry of, and physical characteristics influencing, the thickness of the lateral abdominal muscles at rest and during abdominal exercises were examined in 57 healthy subjects (20 men, 37 women; aged 22-62 years). M-mode ultrasound images were recorded from the abdominal muscles at rest and during abdominal hollowing exercises in hook-lying. The fascial lines bordering the transvs. abdominis, obliquus internus and obliquus externus were digitized and the absolute thickness, relative thickness (% of total lateral thickness) and contraction ratio (thickness during hollowing/thickness at rest), as well as the asymmetry (difference between sides expressed as a percent of the smallest value for the two sides) for each of these parameters were determined for each muscle. Both at rest and during hollowing, obliquus internus was the thickest and transvs. abdominis the thinnest muscle. There were no significant differences between left and right sides for group mean thicknesses of any muscle; however, individual asymmetries were evident, with mean values for the different muscles ranging from 11% to 26%; asymmetry was much less for the contraction ratios (mean % side differences, 5-14% depending on muscle). Body mass was the most significant positive predictor of absolute muscle thickness, for all muscles at rest and during hollowing, accounting for 30-44% variance. Body mass index explained 20-30% variance in transvs. abdominis contraction ratio (negative relationship). The influence of these confounders must be considered in comparative studies of healthy controls and back pain patients, unless groups are very carefully matched. Asymmetries observed in patients should be interpreted with caution, as they are also common in healthy subjects.
Topics: Abdominal Muscles; Adult; Anthropometry; Body Mass Index; Body Weight; Exercise; Female; Humans; Male; Middle Aged; Muscle Contraction; Rest; Sex Characteristics; Supine Position; Ultrasonography; Young Adult
PubMed: 19172732
DOI: 10.1111/j.1469-7580.2008.00946.x