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Simon Green - One of the best experts on this subject based on the ideXlab platform.
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effect of hypoxia on the dynamic response of Hyperaemia in the contracting human calf muscle
Experimental Physiology, 2013Co-Authors: Joseph Donnelly, Simon GreenAbstract:New Findings • What is the central question of this study?The effect of hypoxia on the dynamic response of muscle Hyperaemia during exercise is not known. • What is the main finding and its importance?Demonstrates that the effect of hypoxia on muscle Hyperaemia is very rapid, occurring within the first 2–3 contractions of exercise and before the conventional oxygen-dependent processes would exert their effects. Although systemic hypoxia increases the muscle hyperaemic response during ‘steady-state’ exercise, its effect on the dynamic characteristics of this response is not clear. In the present study, we first established that hypoxia increases the steady-state hyperaemic response at low workloads during calf exercise. To study dynamic aspects of this response, eight subjects performed eight exercise trials while breathing a normoxic (fractional inspired O2= 0.2094) or hypoxic gas mixture (fractional inspired O2= 0.105). Subjects performed intermittent contractions (1 s) of the calf muscle at 20% maximal voluntary contraction, and the leg blood flow (LBF), leg vascular conductance (LVC) and EMG activities of the triceps surae muscles were measured during each contraction–relaxation period (3 s). The LBF and LVC responses were averaged for each subject and fitted using a four-phase, exponential growth and decay function. Hypoxia evoked significant increases in the change in LBF (15%) and LVC (23%) from the start to the end of exercise, as well as the amplitude of the rapid growth phase of LBF and LVC (21%). Similar, but non-significant, effects on the amplitude of the slow growth phase of LBF (P= 0.08) and LVC (P= 0.10) were observed. By contrast, hypoxia had no effect on temporal parameters of these growth phases, parameters defining the decay phases or EMG activities. These results suggest that the effect of hypoxia on exercise Hyperaemia is targeted at the rapid and perhaps the slow growth phase of the response, and is not mediated by a change in the level of muscle activation.
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dynamic response characteristics of Hyperaemia in the human calf muscle effect of exercise intensity and relation to electromyographic activity
European Journal of Applied Physiology, 2012Co-Authors: Elizabeth J Reeder, Simon GreenAbstract:To clarify the structure of the muscle hyperaemic response during submaximal exercise in the supine position, we tested the hypotheses that this response measured in human calf muscle is biphasic or triphasic (growth-only) at low-moderate or high forces, respectively. Ten subjects performed four series of 5-min bout of intermittent contractions from a resting baseline to 30, 60 and 90% of peak force, as well as from an exercise baseline to higher forces. For each exercise transition, leg blood flow (LBF: plethysmography) and leg vascular conductance (LVC) were measured between contractions and averaged across four trials. Six ‘growth-only’ and ‘growth and decay’ models were fitted to these averaged responses and significant differences between their goodness-of-fit were tested statistically. For rest–exercise transitions, triphasic or quadphasic ‘growth and decay’ models provided the best fit to the majority of LBF and LVC responses. The intensity-dependent growth in Hyperaemia was due mainly to a significant increase in amplitude of the rapid growth phase. A fast decay in LBF and LVC occurred at all intensities (mean τ = 4–5 s, mean TD = 9–14 s). A slower decay appeared at the lowest intensity (mean τ = 18–28 s, TD ≅ 90 s) that coincided with a monoexponential decline in EMG activity (mean τ = 23, TD = 87 s). Thus, although biphasic growth is an essential feature of muscle Hyperaemia, rapid and slow decay phases also exist that highlight additional mechanisms which contribute to this dynamic response during exercise.
Janice M Marshall - One of the best experts on this subject based on the ideXlab platform.
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Contribution of prostaglandins to exercise Hyperaemia: workload, ethnicity and sex matter!
The Journal of Physiology, 2019Co-Authors: Abimbola O. Aiku, Janice M MarshallAbstract:The contribution of prostaglandins (PGs) to exercise Hyperaemia is controversial. In this review, we argue this is partly explained by differences in exercise intensity between studies. The effects of cyclooxygenase (COX) inhibition and PG assays indicate that PGs contribute more at moderate to heavy than at light workloads and are mainly released by low tissue O2 . But, the release and actions of PGs also depend on other O2 -dependent dilators including ATP, adenosine and NO. K+ may inhibit the action of PGs and other mediators by causing hyperpolarization, but contributes to the Hyperaemia. Thus, at lighter loads, the influence of PGs may be blunted by K+ , while COX inhibition leads to compensatory increases in other O2 -dependent dilators. In addition, we show that other sources of variability are sex and ethnicity. Our findings indicate that exercise Hyperaemia following rhythmic contractions at 60% maximum voluntary contraction, is smaller in young black African (BA) men and women than in their white European (WE) counterparts, but larger in men than in women of both ethnicities. We propose the larger absolute force in men causes greater vascular occlusion and accumulation of dilators, while blunted Hyperaemia in BAs may reflect lower oxidative capacity and O2 requirement. Nevertheless, COX inhibition attenuated peak Hyperaemia by ∼30% in WE, BA men and WE women, indicating PGs make a substantial contribution in all three groups. There was no effect in BA women. Lack of PG involvement may provide early evidence of endothelial dysfunction, consistent in BA women with their greater risk of cardiovascular disease.
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Effects of modest hyperoxia and oral vitamin C on exercise Hyperaemia and reactive Hyperaemia in healthy young men.
European Journal of Applied Physiology, 2015Co-Authors: Hannah Caruana, Janice M MarshallAbstract:Purpose We have argued that breathing 40 % O2 attenuates exercise Hyperaemia by decreasing production of O2-dependent vasodilators. However, breathing 100 % O2 attenuated endothelium-dependent vasodilatation evoked by acetylcholine and this effect was prevented by vitamin C, implicating reactive oxygen species (ROS). We have therefore used vitamin C to test the hypothesis that 40 % O2 modulates exercise Hyperaemia and reactive Hyperaemia independently of ROS.
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contribution of non endothelium dependent substances to exercise Hyperaemia are they o2 dependent
The Journal of Physiology, 2012Co-Authors: Janice M Marshall, Clare J RayAbstract:This review considers the contributions to exercise Hyperaemia of substances released into the interstitial fluid, with emphasis on whether they are endothelium dependent or O2 dependent. The early phase of exercise Hyperaemia is attributable to K+ released from contracting muscle fibres and acting extraluminally on arterioles. Hyperpolarization of vascular smooth muscle and endothelial cells induced by K+ may also facilitate the maintained phase, for example by facilitating conduction of dilator signals upstream. ATP is released into the interstitium from muscle fibres, at least in part through cystic fibrosis transmembrane conductance regulator-associated channels, following the fall in intracellular H+. ATP is metabolized by ectonucleotidases to adenosine, which dilates arterioles via A2A receptors, in a nitric oxide-independent manner. Evidence is presented that the rise in arterial achieved by breathing 40% O2 attenuates efflux of H+ and lactate, thereby decreasing the contribution that adenosine makes to exercise Hyperaemia; efflux of inorganic phosphate and its contribution may likewise be attenuated. Prostaglandins (PGs), PGE2 and PGI2, also accumulate in the interstitium during exercise, and breathing 40% O2 abolished the contribution of PGs to exercise Hyperaemia. This suggests that PGE2 released from muscle fibres and PGI2 released from capillaries and venular endothelium by a fall in their local act extraluminally to dilate arterioles. Although modest hyperoxia attenuates exercise Hyperaemia by improving O2 supply, limiting the release of O2-dependent adenosine and PGs, higher O2 concentrations may have adverse effects. Evidence is presented that breathing 100% O2 limits exercise Hyperaemia by generating O2−, which inactivates nitric oxide and decreases PG synthesis.
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Contribution of non‐endothelium‐dependent substances to exercise Hyperaemia: are they O2 dependent?
The Journal of Physiology, 2012Co-Authors: Janice M Marshall, Clare J RayAbstract:This review considers the contributions to exercise Hyperaemia of substances released into the interstitial fluid, with emphasis on whether they are endothelium dependent or O2 dependent. The early phase of exercise Hyperaemia is attributable to K+ released from contracting muscle fibres and acting extraluminally on arterioles. Hyperpolarization of vascular smooth muscle and endothelial cells induced by K+ may also facilitate the maintained phase, for example by facilitating conduction of dilator signals upstream. ATP is released into the interstitium from muscle fibres, at least in part through cystic fibrosis transmembrane conductance regulator-associated channels, following the fall in intracellular H+. ATP is metabolized by ectonucleotidases to adenosine, which dilates arterioles via A2A receptors, in a nitric oxide-independent manner. Evidence is presented that the rise in arterial achieved by breathing 40% O2 attenuates efflux of H+ and lactate, thereby decreasing the contribution that adenosine makes to exercise Hyperaemia; efflux of inorganic phosphate and its contribution may likewise be attenuated. Prostaglandins (PGs), PGE2 and PGI2, also accumulate in the interstitium during exercise, and breathing 40% O2 abolished the contribution of PGs to exercise Hyperaemia. This suggests that PGE2 released from muscle fibres and PGI2 released from capillaries and venular endothelium by a fall in their local act extraluminally to dilate arterioles. Although modest hyperoxia attenuates exercise Hyperaemia by improving O2 supply, limiting the release of O2-dependent adenosine and PGs, higher O2 concentrations may have adverse effects. Evidence is presented that breathing 100% O2 limits exercise Hyperaemia by generating O2−, which inactivates nitric oxide and decreases PG synthesis.
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elucidation in the rat of the role of adenosine and a2a receptors in the Hyperaemia of twitch and tetanic contractions
The Journal of Physiology, 2009Co-Authors: Clare J Ray, Janice M MarshallAbstract:Adenosine is implicated in playing a role in blood flow responses to situations where O2 delivery is reduced (hypoxia) or O2 consumption is increased (exercise). Strong isometric contractions have been shown to limit vasodilatation, potentially leading to a greater mismatch between and than during twitch contractions. Thus, we hypothesized that adenosine makes a greater contribution to the Hyperaemia associated with isometric tetanic than isometric twitch contractions and aimed to elucidate the adenosine-receptor subtypes involved in the response. In four groups of anaesthetized rats, arterial blood pressure (ABP), femoral blood flow (FBF) and tension in the extensor digitorum longus muscle were recorded; isometric twitch and tetanic contractions were evoked by stimulation of the sciatic nerve for 5 min at 4 Hz and 40 Hz, respectively. Groups 1 (twitch) and 3 (tetanic) were time controls for Groups 2 and 4, which received the selective A2A-receptor antagonist ZM241385 before the third and 8-sulphophenyltheophylline (8-SPT; a non-selective adenosine receptor antagonist) before the fourth contraction. Time controls showed consistent tension and hyperaemic responses: twitch and tetanic contractions were associated with a 3-fold and 2.5-fold increase in femoral vascular conductance (FVC, FBF/ABP) from baseline, respectively. ZM241385 reduced these responses by 14% and as much as 25%, respectively; 8-SPT had no further effect. We propose that, while twitch contractions produce a larger Hyperaemia, adenosine acting via A2A-receptors plays a greater role in the Hyperaemia associated with tetanic contraction. These results are considered in relation to the A1-receptor-mediated muscle dilatation evoked by systemic hypoxia.
Clare J Ray - One of the best experts on this subject based on the ideXlab platform.
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contribution of non endothelium dependent substances to exercise Hyperaemia are they o2 dependent
The Journal of Physiology, 2012Co-Authors: Janice M Marshall, Clare J RayAbstract:This review considers the contributions to exercise Hyperaemia of substances released into the interstitial fluid, with emphasis on whether they are endothelium dependent or O2 dependent. The early phase of exercise Hyperaemia is attributable to K+ released from contracting muscle fibres and acting extraluminally on arterioles. Hyperpolarization of vascular smooth muscle and endothelial cells induced by K+ may also facilitate the maintained phase, for example by facilitating conduction of dilator signals upstream. ATP is released into the interstitium from muscle fibres, at least in part through cystic fibrosis transmembrane conductance regulator-associated channels, following the fall in intracellular H+. ATP is metabolized by ectonucleotidases to adenosine, which dilates arterioles via A2A receptors, in a nitric oxide-independent manner. Evidence is presented that the rise in arterial achieved by breathing 40% O2 attenuates efflux of H+ and lactate, thereby decreasing the contribution that adenosine makes to exercise Hyperaemia; efflux of inorganic phosphate and its contribution may likewise be attenuated. Prostaglandins (PGs), PGE2 and PGI2, also accumulate in the interstitium during exercise, and breathing 40% O2 abolished the contribution of PGs to exercise Hyperaemia. This suggests that PGE2 released from muscle fibres and PGI2 released from capillaries and venular endothelium by a fall in their local act extraluminally to dilate arterioles. Although modest hyperoxia attenuates exercise Hyperaemia by improving O2 supply, limiting the release of O2-dependent adenosine and PGs, higher O2 concentrations may have adverse effects. Evidence is presented that breathing 100% O2 limits exercise Hyperaemia by generating O2−, which inactivates nitric oxide and decreases PG synthesis.
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Contribution of non‐endothelium‐dependent substances to exercise Hyperaemia: are they O2 dependent?
The Journal of Physiology, 2012Co-Authors: Janice M Marshall, Clare J RayAbstract:This review considers the contributions to exercise Hyperaemia of substances released into the interstitial fluid, with emphasis on whether they are endothelium dependent or O2 dependent. The early phase of exercise Hyperaemia is attributable to K+ released from contracting muscle fibres and acting extraluminally on arterioles. Hyperpolarization of vascular smooth muscle and endothelial cells induced by K+ may also facilitate the maintained phase, for example by facilitating conduction of dilator signals upstream. ATP is released into the interstitium from muscle fibres, at least in part through cystic fibrosis transmembrane conductance regulator-associated channels, following the fall in intracellular H+. ATP is metabolized by ectonucleotidases to adenosine, which dilates arterioles via A2A receptors, in a nitric oxide-independent manner. Evidence is presented that the rise in arterial achieved by breathing 40% O2 attenuates efflux of H+ and lactate, thereby decreasing the contribution that adenosine makes to exercise Hyperaemia; efflux of inorganic phosphate and its contribution may likewise be attenuated. Prostaglandins (PGs), PGE2 and PGI2, also accumulate in the interstitium during exercise, and breathing 40% O2 abolished the contribution of PGs to exercise Hyperaemia. This suggests that PGE2 released from muscle fibres and PGI2 released from capillaries and venular endothelium by a fall in their local act extraluminally to dilate arterioles. Although modest hyperoxia attenuates exercise Hyperaemia by improving O2 supply, limiting the release of O2-dependent adenosine and PGs, higher O2 concentrations may have adverse effects. Evidence is presented that breathing 100% O2 limits exercise Hyperaemia by generating O2−, which inactivates nitric oxide and decreases PG synthesis.
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elucidation in the rat of the role of adenosine and a2a receptors in the Hyperaemia of twitch and tetanic contractions
The Journal of Physiology, 2009Co-Authors: Clare J Ray, Janice M MarshallAbstract:Adenosine is implicated in playing a role in blood flow responses to situations where O2 delivery is reduced (hypoxia) or O2 consumption is increased (exercise). Strong isometric contractions have been shown to limit vasodilatation, potentially leading to a greater mismatch between and than during twitch contractions. Thus, we hypothesized that adenosine makes a greater contribution to the Hyperaemia associated with isometric tetanic than isometric twitch contractions and aimed to elucidate the adenosine-receptor subtypes involved in the response. In four groups of anaesthetized rats, arterial blood pressure (ABP), femoral blood flow (FBF) and tension in the extensor digitorum longus muscle were recorded; isometric twitch and tetanic contractions were evoked by stimulation of the sciatic nerve for 5 min at 4 Hz and 40 Hz, respectively. Groups 1 (twitch) and 3 (tetanic) were time controls for Groups 2 and 4, which received the selective A2A-receptor antagonist ZM241385 before the third and 8-sulphophenyltheophylline (8-SPT; a non-selective adenosine receptor antagonist) before the fourth contraction. Time controls showed consistent tension and hyperaemic responses: twitch and tetanic contractions were associated with a 3-fold and 2.5-fold increase in femoral vascular conductance (FVC, FBF/ABP) from baseline, respectively. ZM241385 reduced these responses by 14% and as much as 25%, respectively; 8-SPT had no further effect. We propose that, while twitch contractions produce a larger Hyperaemia, adenosine acting via A2A-receptors plays a greater role in the Hyperaemia associated with tetanic contraction. These results are considered in relation to the A1-receptor-mediated muscle dilatation evoked by systemic hypoxia.
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Nitric oxide (NO) does not contribute to the generation or action of adenosine during exercise Hyperaemia in rat hindlimb
The Journal of Physiology, 2009Co-Authors: Clare J Ray, Janice M MarshallAbstract:Exercise Hyperaemia is partly mediated by adenosine A2A-receptors. Adenosine can evoke nitric oxide (NO) release via endothelial A2A-receptors, but the role for NO in exercise Hyperaemia is controversial. We have investigated the contribution of NO to Hyperaemia evoked by isometric twitch contractions in its own right and in interaction with adenosine. In three groups of anaesthetized rats the effect of A2A-receptor inhibition with ZM241385 on femoral vascular conductance (FVC) and hindlimb O2 consumption at rest and during isometric twitch contractions (4 Hz) was tested (i) after NO synthase inhibition with l-NAME, and when FVC had been restored by infusion of (ii) an NO donor (SNAP) or (iii) cell-permeant cGMP. Exercise Hyperaemia was significantly reduced (32%) by l-NAME and further significantly attenuated by ZM241385 (60% from control). After restoring FVC with SNAP or 8-bromo-cGMP, l-NAME did not affect exercise Hyperaemia, but ZM241385 still significantly reduced the Hyperaemia by 25%. There was no evidence that NO limited muscle during contraction. These results indicate that NO is not required for adenosine release during contraction and that adenosine released during contraction does not depend on new synthesis of NO to produce vasodilatation. They also substantiate our general hypothesis that the mechanisms by which adenosine contributes to muscle vasodilatation during systemic hypoxia and exercise are different: we propose that, during muscle contraction, adenosine is released from skeletal muscle fibres independently of NO and acts directly on A2A-receptors on the vascular smooth muscle to cause vasodilatation.
Stefan P Mortensen - One of the best experts on this subject based on the ideXlab platform.
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vasodilator interactions in skeletal muscle blood flow regulation
The Journal of Physiology, 2012Co-Authors: Ylva Hellsten, Michael Nyberg, Lotte Jensen, Stefan P MortensenAbstract:During exercise, oxygen delivery to skeletal muscle is elevated to meet the increased oxygen demand. The increase in blood flow to skeletal muscle is achieved by vasodilators formed locally in the muscle tissue, either on the intraluminal or on the extraluminal side of the blood vessels. A number of vasodilators have been shown to bring about this increase in blood flow and, importantly, interactions between these compounds seem to be essential for the precise regulation of blood flow. Two compounds stand out as central in these vasodilator interactions: nitric oxide (NO) and prostacyclin. These two vasodilators are both stimulated by several compounds, e.g. adenosine, ATP, acetylcholine and bradykinin, and are affected by mechanically induced signals, such as shear stress. NO and prostacyclin have also been shown to interact in a redundant manner where one system can take over when formation of the other is compromised. Although numerous studies have examined the role of single and multiple pharmacological inhibition of different vasodilator systems, and important vasodilators and interactions have been identified, a large part of the exercise hyperaemic response remains unexplained. It is plausible that this remaining Hyperaemia may be explained by cAMP- and cGMP-independent smooth muscle relaxation, such as effects of endothelial derived hyperpolarization factors (EDHFs) or through metabolic modulation of sympathetic effects. The nature and role of EDHF as well as potential novel mechanisms in muscle blood flow regulation remain to be further explored to fully elucidate the regulation of exercise Hyperaemia.
J. E. Tooke - One of the best experts on this subject based on the ideXlab platform.
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reduced microvascular Hyperaemia in subjects at risk of developing type 2 non insulin dependent diabetes mellitus
Diabetologia, 1994Co-Authors: A J Jaap, M S Hammersley, A C Shore, J. E. TookeAbstract:Abnormalities of microvascular function may be important in the pathogenesis of diabetic microangiopathy. As such changes are already present at diagnosis in patients with Type 2 (non-insulin-dependent) diabetes mellitus, subjects at risk of developing the disease, who had elevated fasting plasma glucose concentrations below the diabetic range, were studied. The maximal microvascular hyperaemic response to local heating was determined in the feet of 11 subjects with fasting hyperglycaemia and 11 age- and sex-matched control subjects. There was reduced maximal Hyperaemia in the subjects with fasting hyperglycaemia (1.01 [0.71-1.57]V, median and range), when compared to control subjects (1.41 [1.32-2.13]V, p < 0.001). It is unlikely that this limited vasodilation is a result of the mild degree of hyperglycaemia observed in the subjects included in this study. Further studies are therefore required to address the possible mechanisms of limited microvascular reactivity in subjects at risk of developing Type 2 diabetes.
