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The Journal of Physiology

Cover image for Vol. 588 Issue 23

December 2010

Volume 588, Issue 23

Pages 1–4847

  1. Issue Information

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. JOURNAL CLUB
    5. TOPICAL REVIEWS
    6. SPECIAL SECTION REVIEWS: VOLTAGE AND ION SENSING CHANNELS: THREE VIEWS OF THE SAME TALE
    7. MOLECULAR AND CELLULAR
    8. NEUROSCIENCE
    9. CARDIOVASCULAR
    10. RESPIRATORY
    11. SKELETAL MUSCLE AND EXERCISE
    12. INTEGRATIVE
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      Issue Information (pages 1–6)

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.58823

  2. PERSPECTIVES

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. JOURNAL CLUB
    5. TOPICAL REVIEWS
    6. SPECIAL SECTION REVIEWS: VOLTAGE AND ION SENSING CHANNELS: THREE VIEWS OF THE SAME TALE
    7. MOLECULAR AND CELLULAR
    8. NEUROSCIENCE
    9. CARDIOVASCULAR
    10. RESPIRATORY
    11. SKELETAL MUSCLE AND EXERCISE
    12. INTEGRATIVE
    1. You have free access to this content
      Going to altitude? Bring your vitamins! (pages 4603–4604)

      Carsten Lundby

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.200899

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      Muscle capillary supply takes the load (pages 4607–4608)

      Stuart Egginton

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.200378

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      Synchronicity, cycles and synaptic signalling in the colon (page 4611)

      James J. Galligan

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.200766

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      Fasting during exercise for fitness during feasting? (pages 4613–4614)

      Leonie K. Heilbronn

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.200790

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      Angiogenesis – may the force be with you! (pages 4615–4616)

      Stuart Egginton

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.201012

  3. JOURNAL CLUB

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. JOURNAL CLUB
    5. TOPICAL REVIEWS
    6. SPECIAL SECTION REVIEWS: VOLTAGE AND ION SENSING CHANNELS: THREE VIEWS OF THE SAME TALE
    7. MOLECULAR AND CELLULAR
    8. NEUROSCIENCE
    9. CARDIOVASCULAR
    10. RESPIRATORY
    11. SKELETAL MUSCLE AND EXERCISE
    12. INTEGRATIVE
    1. You have full text access to this OnlineOpen article
      Life of mice – development of cardiac energetics (pages 4617–4619)

      Ardo Illaste, Mari Kalda, David W. Schryer and Mervi Sepp

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.199901

  4. TOPICAL REVIEWS

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. JOURNAL CLUB
    5. TOPICAL REVIEWS
    6. SPECIAL SECTION REVIEWS: VOLTAGE AND ION SENSING CHANNELS: THREE VIEWS OF THE SAME TALE
    7. MOLECULAR AND CELLULAR
    8. NEUROSCIENCE
    9. CARDIOVASCULAR
    10. RESPIRATORY
    11. SKELETAL MUSCLE AND EXERCISE
    12. INTEGRATIVE
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      Neuroeffector apparatus in gastrointestinal smooth muscle organs (pages 4621–4639)

      Kenton M. Sanders, Sung Jin Hwang and Sean M. Ward

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.196030

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      Structure to function: muscle failure in critically ill patients (pages 4641–4648)

      Zudin Puthucheary, Hugh Montgomery, John Moxham, Stephen Harridge and Nicholas Hart

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.197632

  5. SPECIAL SECTION REVIEWS: VOLTAGE AND ION SENSING CHANNELS: THREE VIEWS OF THE SAME TALE

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. JOURNAL CLUB
    5. TOPICAL REVIEWS
    6. SPECIAL SECTION REVIEWS: VOLTAGE AND ION SENSING CHANNELS: THREE VIEWS OF THE SAME TALE
    7. MOLECULAR AND CELLULAR
    8. NEUROSCIENCE
    9. CARDIOVASCULAR
    10. RESPIRATORY
    11. SKELETAL MUSCLE AND EXERCISE
    12. INTEGRATIVE
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      A global synergy of ions and voltage? (page 4649)

      Yasushi Okamura

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.201202

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      Physiological roles of voltage-gated proton channels in leukocytes (pages 4659–4665)

      Nicolas Demaurex and Antoun El Chemaly

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.194225

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      The role of Hv1 and CatSper channels in sperm activation (pages 4667–4672)

      Polina V. Lishko and Yuriy Kirichok

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.194142

  6. MOLECULAR AND CELLULAR

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. JOURNAL CLUB
    5. TOPICAL REVIEWS
    6. SPECIAL SECTION REVIEWS: VOLTAGE AND ION SENSING CHANNELS: THREE VIEWS OF THE SAME TALE
    7. MOLECULAR AND CELLULAR
    8. NEUROSCIENCE
    9. CARDIOVASCULAR
    10. RESPIRATORY
    11. SKELETAL MUSCLE AND EXERCISE
    12. INTEGRATIVE
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      Voltage-dependent block by internal spermine of the murine inwardly rectifying K+ channel, Kir2.1, with asymmetrical K+ concentrations (pages 4673–4681)

      Hiroko Matsuda, Mikio Hayashi and Masayoshi Okada

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.194480

      Inward rectification, whereby K+ conductance increases under hyperpolarization and decreases under depolarization, is ascribed mainly to a voltage-dependent block of the channel pore by intracellular polyamines and Mg2+. The blocking effect of intracellular Mg2+ in cardiac inwardly rectifying K+ channels depends on driving force when EK is altered by changing external K+ and on voltage when EK is altered by changing internal K+. We studied effects of internal spermine on outward single-channel currents through a strongly inwardly rectifying K+ channel (Kir2.1) at asymmetrical K+ concentrations (30 mm external and 150 mm internal K+) and compared them with those obtained previously at symmetrical K+ concentrations (150 mm external and internal K+). The blocking kinetics depends on driving force to produce driving force-dependent inward rectification when EK is altered by changing external K+.

  7. NEUROSCIENCE

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. JOURNAL CLUB
    5. TOPICAL REVIEWS
    6. SPECIAL SECTION REVIEWS: VOLTAGE AND ION SENSING CHANNELS: THREE VIEWS OF THE SAME TALE
    7. MOLECULAR AND CELLULAR
    8. NEUROSCIENCE
    9. CARDIOVASCULAR
    10. RESPIRATORY
    11. SKELETAL MUSCLE AND EXERCISE
    12. INTEGRATIVE
    1. RAPID REPORT

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      Acute hyperbilirubinaemia induces presynaptic neurodegeneration at a central glutamatergic synapse (pages 4683–4693)

      Martin D. Haustein, David J. Read, Joern R. Steinert, Nadia Pilati, David Dinsdale and Ian D. Forsythe

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.199778

      During jaundice bilirubin, a yellowish pigment produced during the degradation of haemoglobin from red blood cells, reaches sufficient concentrations in the blood for it to enter the brain. In severe cases this leads to deafness and neurological complications, particularly in newborn infants. It is not clear how bilirubin disrupts hearing. Previous reports have shown that the sensory hair cells of the inner ear are spared, so we investigated the damage caused by bilirubin further along the auditory pathway in the brain. We found that synaptic transmission was severely impaired after 18 hours of exposure to bilirubin. This failure in signal transmission was due to structural damage of the nerve endings rather than the nerve itself. The findings of this study show that bilirubin toxicity is a neurodegenerative disease and suggest that the mechanism involves nitric oxide.

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      Metaplasticity of horizontal connections in the vicinity of focal laser lesions in rat visual cortex (pages 4695–4703)

      B. Imbrosci, U. T. Eysel and T. Mittmann

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.198192

      Focal traumatic brain injuries lead to cell damage and functional loss, which can be compensated, at least in part, by a functional reorganization of the neighbouring undamaged neurons. Here, we show that a focal laser lesion in the visual cortex of rats leads to a facilitated long-term potentiation (LTP) of synapses located at intracortical horizontal connections in the vicinity of the injury. This lesion-induced facilitation of cellular learning processes at horizontal cortical connections can be a helpful mechanism to compensate the brain injury-mediated functional loss.

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      Expression of early growth response protein 1 in vasopressin neurones of the rat anterior olfactory nucleus following social odour exposure (pages 4705–4717)

      Douglas W. Wacker, Vicky A. Tobin, Julia Noack, Valerie R. Bishop, Adrian J. Duszkiewicz, Mario Engelmann, Simone L. Meddle and Mike Ludwig

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.196139

      In addition to its well-known peripheral functions, the neurohormone vasopressin modulates social behaviours in mammals, including humans. The anterior olfactory nucleus (AON) is a brain region involved in processing odours. We have discovered a new population of vasopressin neurones in the AON. These vasopressin cells also express other neurochemicals, such as GABA. Here we demonstrate that vasopressin cells in particular subregions of the AON are activated in response to the same species smells. Predator odours, like fox and cat, do not activate vasopressin cells in the AON indicating a role of this brain region in the coding of same species odour information.

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      The C-terminal domain of βIV-spectrin is crucial for KCNQ2 aggregation and excitability at nodes of Ranvier (pages 4719–4730)

      Jérôme J. Devaux

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.196022

      Nodes of Ranvier are highly specialized axonal domains that regenerate the neuronal activity and allow the rapid propagation of information along the nerves. This study shows that βIV-spectrin, an intracellular protein, is critical for the organization of the nodes of Ranvier, notably for the distribution of KCNQ2 potassium channels along axons. This study provides knowledge of the role of KCNQ2 in nerves and indicates that KCNQ2 channels dampen aberrant neuronal activities that may otherwise generate involuntary muscle movements.

  8. CARDIOVASCULAR

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. JOURNAL CLUB
    5. TOPICAL REVIEWS
    6. SPECIAL SECTION REVIEWS: VOLTAGE AND ION SENSING CHANNELS: THREE VIEWS OF THE SAME TALE
    7. MOLECULAR AND CELLULAR
    8. NEUROSCIENCE
    9. CARDIOVASCULAR
    10. RESPIRATORY
    11. SKELETAL MUSCLE AND EXERCISE
    12. INTEGRATIVE
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      Differential sensitivity of Ca2+ wave and Ca2+ spark events to ruthenium red in isolated permeabilised rabbit cardiomyocytes (pages 4731–4742)

      N. MacQuaide, H. R. Ramay, E. A. Sobie and G. L. Smith

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.193375

      Heart cells contract due to a rapid electrical event on the surface membrane that triggers a homogeneous release of Ca2+ from the sarcoplasmic reticulum (SR) into the cytoplasm. The SR can release Ca2+ without the electrical trigger in two ways: (i) a spatially limited Ca2+‘spark’ or (ii) a Ca2+‘wave’ that propagates throughout the cell. The latter event is thought to cause arrhythmias in the whole heart. This study provides experimental evidence to suggest that Ca2+ waves are not simply due to sequential activation of Ca2+ sparks. Instead SR Ca2+ release other than a spark appears to be essential for propagation of the Ca2+ wave. Pharmacological blocking of the ‘non-spark’ form of the release may be an effective strategy to prevent arrhythmias without compromising normal heart function.

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      Ca2+ spark-dependent and -independent sarcoplasmic reticulum Ca2+ leak in normal and failing rabbit ventricular myocytes (pages 4743–4757)

      Aleksey V. Zima, Elisa Bovo, Donald M. Bers and Lothar A. Blatter

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.197913

      Contraction of the heart relies on calcium stored in the sarcoplasmic reticulum (SR) that is released and subsequently taken up again with every heart beat. Calcium content of the SR is determined by the balance between calcium pump activity and passive calcium leak. SR calcium leak plays an important role in the normal and diseased heart. We found that the ryanodine receptor, a calcium release channel in the SR, is the main source of calcium leak of ventricular myocytes. In the SR ryanodine receptors are organized in individual clusters. Depending on the amount of calcium stored, calcium leak can occur as openings of a single ryanodine receptor, as simultaneous activation of multiple channels in a cluster or through pathways that do not involve the ryanodine receptor. We also found that calcium leak through ryanodine receptors is significantly increased in myocytes from failing hearts leading to impaired cardiac function.

  9. RESPIRATORY

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. JOURNAL CLUB
    5. TOPICAL REVIEWS
    6. SPECIAL SECTION REVIEWS: VOLTAGE AND ION SENSING CHANNELS: THREE VIEWS OF THE SAME TALE
    7. MOLECULAR AND CELLULAR
    8. NEUROSCIENCE
    9. CARDIOVASCULAR
    10. RESPIRATORY
    11. SKELETAL MUSCLE AND EXERCISE
    12. INTEGRATIVE
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      Lung volume does not alter the distribution of pulmonary perfusion in dependent lung in supine humans (pages 4759–4768)

      Susan R. Hopkins, Tatsuya J. Arai, A. Cortney Henderson, David L. Levin, Richard B. Buxton and G. Kim Prisk

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.196063

      The lung is subject to multiple influences that affect its function. In particular the effect of gravity has attracted considerable interest, especially as it relates to the distribution of blood flow. In the most gravitationally dependent part of the lung, blood flow is reduced, and this region is known as Zone 4. Zone 4 has been suggested to result from increased resistance in some of the blood vessels, and this effect is thought to be the smallest when the lung is at a high volume as the elastic structures of the lung hold the vessels open minimizing resistance. Using novel magnetic resonance imaging techniques to measure blood flow, this study shows that the distribution of blood flow in the dependent lung is unchanged when the lung volume is changed and suggests that the intrinsic structure of the vessels is a more likely explanation for this behaviour.

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      Phenotypic distinctions between neural crest and placodal derived vagal C-fibres in mouse lungs (pages 4769–4783)

      Christina Nassenstein, Thomas E. Taylor-Clark, Allen C. Myers, Fei Ru, Rajender Nandigama, Weston Bettner and Bradley J. Undem

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.195339

      Two major types of nociceptors have been described in dorsal root ganglia. In comparison, little is known about the vagal nociceptor subtypes. The vagus nerves provide much of the capsaicin-sensitive nociceptive innervation to visceral tissues, e.g. the lung, and are likely to contribute to the overall pathophysiology of visceral inflammatory diseases. Our data support the hypothesis that vagal nociceptors innervating the lung comprise at least two major subtypes. We observed differences in their function, gene expression profile and embryonic origin. Due to these distinctions, each type will respond to noxious or inflammatory conditions in their own unique manner.

  10. SKELETAL MUSCLE AND EXERCISE

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. JOURNAL CLUB
    5. TOPICAL REVIEWS
    6. SPECIAL SECTION REVIEWS: VOLTAGE AND ION SENSING CHANNELS: THREE VIEWS OF THE SAME TALE
    7. MOLECULAR AND CELLULAR
    8. NEUROSCIENCE
    9. CARDIOVASCULAR
    10. RESPIRATORY
    11. SKELETAL MUSCLE AND EXERCISE
    12. INTEGRATIVE
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      Lactate per se improves the excitability of depolarized rat skeletal muscle by reducing the Cl conductance (pages 4785–4794)

      Frank Vincenzo de Paoli, Niels Ørtenblad, Thomas Holm Pedersen, Rasmus Jørgensen and Ole Bækgaard Nielsen

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.196568

      Contrary to the general belief that the accumulation of lactate in muscles is an important cause of exercise-induced fatigue, several recent studies have demonstrated effects of lactate that indicate that its presence during work is beneficial for exercise performance. In line with this, we show in this study that, by inhibiting chloride channels in the muscle fibres, lactate can improve the tolerance of muscles to elevated extracellular potassium – an effect that may be important for the maintenance of muscle function during exercise.

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      Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle (pages 4795–4810)

      Christopher G. R. Perry, James Lally, Graham P. Holloway, George J. F. Heigenhauser, Arend Bonen and Lawrence L. Spriet

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.199448

      It is believed that exercise training stimulates mitochondrial biogenesis by repeatedly increasing mRNA contents for mitochondrial proteins via activation of specific nuclear transcription proteins. These transcription proteins may also increase early during training. The timing of these responses may be important and occur in unique patterns but this has not been determined in human muscle. We show that mitochondrial biogenesis occurs very rapidly (3 exercise sessions) with steady increases thereafter. Furthermore, only one session increased the content of two important transcription factors (PGC-1α and PPARα) with others increasing after 3–5 sessions. Numerous mitochondrial and transcription protein increases appeared to result from repeated short bursts in their mRNA contents which occurred in very distinct patterns. These results show that mitochondrial biogenesis occurs rapidly and suggests the contribution of specific transcription proteins to this process may be time-dependent. This information may help our understanding of how exercise improves muscle metabolic capacities.

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      Cellular mechanisms underlying temporal changes in skeletal muscle protein synthesis and breakdown during chronic β-adrenoceptor stimulation in mice (pages 4811–4823)

      René Koopman, Stefan M. Gehrig, Bertrand Léger, Jennifer Trieu, Stéphane Walrand, Kate T. Murphy and Gordon S. Lynch

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.196725

      Chronic stimulation of β-adrenoceptors with β-agonists can induce skeletal muscle growth and could represent an effective treatment for the muscle wasting in ageing, sepsis, cancer cachexia, and muscle diseases. To better understand the mechanisms of β-agonist-mediated muscle growth we examined the muscle anabolic response in mice after acute or chronic treatment with the β-agonist formoterol. We found that muscle protein synthesis was increased only after chronic treatment, which was associated with reduced indicators for muscle breakdown and enhanced anabolic signalling. This knowledge enhances our understanding of the pathways that maintain skeletal muscle homeostasis with implications for treating muscle wasting conditions.

  11. INTEGRATIVE

    1. Top of page
    2. Issue Information
    3. PERSPECTIVES
    4. JOURNAL CLUB
    5. TOPICAL REVIEWS
    6. SPECIAL SECTION REVIEWS: VOLTAGE AND ION SENSING CHANNELS: THREE VIEWS OF THE SAME TALE
    7. MOLECULAR AND CELLULAR
    8. NEUROSCIENCE
    9. CARDIOVASCULAR
    10. RESPIRATORY
    11. SKELETAL MUSCLE AND EXERCISE
    12. INTEGRATIVE
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      Sympathetic neural activation: an ordered affair (pages 4825–4836)

      Craig D. Steinback, Aryan Salmanpour, Toni Breskovic, Zeljko Dujic and J. Kevin Shoemaker

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.195941

      The sympathetic nervous system is an important controller of blood pressure and blood flow to critical tissues and organs. In other neural systems (e.g. the skeletal motor system) there is a well understood pattern of neural recruitment during activation. Alternatively, our understanding of how sympathetic neurones are coordinated during stress is limited. We demonstrate that during stress otherwise silent sympathetic neurones are activated in an order based on neuronal size (from smallest to largest). This recruitment pattern is similar to what is known in other neural systems. This information has important implications for how blood pressure and blood flow are controlled, and the malleability of sympathetic activation in health and disease.

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      High-altitude pulmonary hypertension is associated with a free radical-mediated reduction in pulmonary nitric oxide bioavailability (pages 4837–4847)

      Damian M. Bailey, Christoph Dehnert, Andrew M. Luks, Elmar Menold, Christian Castell, Guido Schendler, Vitalie Faoro, Mariusz Gutowski, Kevin A. Evans, Sarah Taudorf, Philip E. James, J. McEneny, Ian S. Young, Erik R. Swenson, Heimo Mairbäurl, Peter Bärtsch and Marc M. Berger

      Version of Record online: 30 NOV 2010 | DOI: 10.1113/jphysiol.2010.194704

      What causes pulmonary hypertension at high altitude remains unknown. By measuring the transpulmonary exchange kinetics of redox-reactive biomarkers, this study suggests that hypertension may be related to a free radical-mediated reduction in pulmonary vascular nitric oxide bioavailability due in part to inadequate antioxidant defence. These findings have broader implications for other clinical models of human disease characterised by global hypoxaemia and identify the hypoxic human lungs as a contributory source of oxidative–nitrosative–inflammatory stress.

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