scholarly journals Effect of extraluminal ATP application on vascular tone and blood flow in skeletal muscle: implications for exercise hyperemia

2013 ◽  
Vol 305 (3) ◽  
pp. R281-R290 ◽  
Author(s):  
Michael Nyberg ◽  
Baraa K. Al-Khazraji ◽  
Stefan P. Mortensen ◽  
Dwayne N. Jackson ◽  
Christopher G. Ellis ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Muscle Blood Flow ◽  
Gluteus Maximus ◽  
Underlying Mechanism ◽  
Experimental Models ◽  
Muscle Contractions ◽  
Rat Skeletal Muscle ◽  
Vasodilator Effect ◽  
Exercise Hyperemia

During skeletal muscle contractions, the concentration of ATP increases in muscle interstitial fluid as measured by microdialysis probes. This increase is associated with the magnitude of blood flow, suggesting that interstitial ATP may be important for contraction-induced vasodilation. However, interstitial ATP has solely been described to induce vasoconstriction in skeletal muscle. To examine whether interstitial ATP induces vasodilation in skeletal muscle and to what extent this vasoactive effect is mediated by formation of nitric oxide (NO) and prostanoids, three different experimental models were studied. The rat gluteus maximus skeletal muscle model was used to study changes in local skeletal muscle hemodynamics. Superfused ATP at concentrations found during muscle contractions (1–10 μM) increased blood flow by up to 400%. In this model, the underlying mechanism was also examined by inhibition of NO and prostanoid formation. Inhibition of these systems abolished the vasodilator effect of ATP. Cell-culture experiments verified ATP-induced formation of NO and prostacyclin in rat skeletal muscle microvascular endothelial cells, and ATP-induced formation of NO in rat skeletal muscle cells. To confirm these findings in humans, ATP was infused into skeletal muscle interstitium of healthy subjects via microdialysis probes and found to increase muscle interstitial concentrations of NO and prostacyclin by ∼60% and ∼40%, respectively. Collectively, these data suggest that a physiologically relevant elevation in interstitial ATP concentrations increases muscle blood flow, indicating that the contraction-induced increase in skeletal muscle interstitial [ATP] is important for exercise hyperemia. The vasodilator effect of ATP application is mediated by NO and prostanoid formation.

Effects of chronic heart failure on skeletal muscle capillary hemodynamics at rest and during contractions

2003 ◽  
Vol 95 (3) ◽  
pp. 1055-1062 ◽  
Author(s):  
Troy E. Richardson ◽  
Casey A. Kindig ◽  
Timothy I. Musch ◽  
David C. Poole
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Chronic Heart Failure ◽  
Muscle Function ◽  
Muscle Blood Flow ◽  
Rat Skeletal Muscle ◽  
Exercise Onset ◽  
Final Response ◽  
Microscopy Techniques

Chronic heart failure (CHF) reduces muscle blood flow at rest and during exercise and impairs muscle function. Using intravital microscopy techniques, we tested the hypothesis that the speed and amplitude of the capillary red blood cell (RBC) velocity ( VRBC) and flux (FRBC) response to contractions would be reduced in CHF compared with control (C) spinotrapezius muscle. The proportion of capillaries supporting continuous RBC flow was less ( P < 0.05) in CHF (0.66 ± 0.04) compared with C (0.84 ± 0.01) muscle at rest and was not significantly altered with contractions. At rest, VRBC (C, 270 ± 62; CHF, 179 ± 14 μm/s) and FRBC (C, 22.4 ± 5.5 vs. CHF, 15.2 ± 1.2 RBCs/s) were reduced (both P < 0.05) in CHF vs. C muscle. Contractions significantly (both P < 0.05) elevated VRBC (C, 428 ± 47 vs. CHF, 222 ± 15 μm/s) and FRBC (C, 44.3 ± 5.5 vs. CHF, 24.0 ± 1.2 RBCs/s) in C and CHF muscle; however, both remained significantly lower in CHF than C. The time to 50% of the final response was slowed (both P < 0.05) in CHF compared with C for both VRBC (C, 8 ± 4; CHF, 56 ± 11 s) and FRBC (C, 11 ± 3; CHF, 65 ± 11 s). Capillary hematocrit increased with contractions in C and CHF muscle but was not different ( P > 0.05) between CHF and C. Thus CHF impairs diffusive and conductive O2 delivery across the rest-to-contractions transition in rat skeletal muscle, which may help explain the slowed O2 uptake on-kinetics manifested in CHF patients at exercise onset.

Vasodilatory mechanisms in contracting skeletal muscle

2004 ◽  
Vol 97 (1) ◽  
pp. 393-403 ◽  
Author(s):  
Philip S. Clifford ◽  
Ylva Hellsten
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Time Course ◽  
Muscle Blood Flow ◽  
Metabolic Demand ◽  
Vasoactive Substances ◽  
Exercise Hyperemia ◽  
Simultaneous Inhibition ◽  
Integrated Response ◽  
Flow Mediated Vasodilation

Skeletal muscle blood flow is closely coupled to metabolic demand, and its regulation is believed to be mainly the result of the interplay of neural vasoconstrictor activity and locally derived vasoactive substances. Muscle blood flow is increased within the first second after a single contraction and stabilizes within ∼30 s during dynamic exercise under normal conditions. Vasodilator substances may be released from contracting skeletal muscle, vascular endothelium, or red blood cells. The importance of specific vasodilators is likely to vary over the time course of flow, from the initial rapid rise to the sustained elevation during steady-state exercise. Exercise hyperemia is therefore thought to be the result of an integrated response of more than one vasodilator mechanism. To date, the identity of vasoactive substances involved in the regulation of exercise hyperemia remains uncertain. Numerous vasodilators such as adenosine, ATP, potassium, hypoxia, hydrogen ion, nitric oxide, prostanoids, and endothelium-derived hyperpolarizing factor have been proposed to be of importance; however, there is little support for any single vasodilator being essential for exercise hyperemia. Because elevated blood flow cannot be explained by the failure of any single vasodilator, a consensus is beginning to emerge for redundancy among vasodilators, where one vasoactive compound may take over when the formation of another is compromised. Conducted vasodilation or flow-mediated vasodilation may explain dilation in vessels (i.e., feed arteries) not directly exposed to vasodilator substances in the interstitium. Future investigations should focus on identifying novel vasodilators and the interaction between vasodilators by simultaneous inhibition of multiple vasodilator pathways.

scholarly journals Mechanical effects of muscle contraction increase intravascular ATP draining quiescent and active skeletal muscle in humans

2013 ◽  
Vol 114 (8) ◽  
pp. 1085-1093 ◽  
Author(s):  
Anne R. Crecelius ◽  
Brett S. Kirby ◽  
Jennifer C. Richards ◽  
Frank A. Dinenno
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Muscle Contraction ◽  
Cuff Pressure ◽  
Muscle Blood Flow ◽  
Muscle Contractions ◽  
Luciferase Assay ◽  
Metabolic Demand ◽  
Mechanical Effects

Intravascular adenosine triphosphate (ATP) evokes vasodilation and is implicated in the regulation of skeletal muscle blood flow during exercise. Mechanical stresses to erythrocytes and endothelial cells stimulate ATP release in vitro. How mechanical effects of muscle contractions contribute to increased plasma ATP during exercise is largely unexplored. We tested the hypothesis that simulated mechanical effects of muscle contractions increase [ATP]venous and ATP effluent in vivo, independent of changes in tissue metabolic demand, and further increase plasma ATP when superimposed with mild-intensity exercise. In young healthy adults, we measured forearm blood flow (FBF) (Doppler ultrasound) and plasma [ATP]v (luciferin-luciferase assay), then calculated forearm ATP effluent (FBF×[ATP]v) during rhythmic forearm compressions (RFC) via a blood pressure cuff at three graded pressures (50, 100, and 200 mmHg; Protocol 1; n = 10) and during RFC at 100 mmHg, 5% maximal voluntary contraction rhythmic handgrip exercise (RHG), and combined RFC + RHG ( Protocol 2; n = 10). [ATP]v increased from rest with each cuff pressure (range 144–161 vs. 64 ± 13 nmol/l), and ATP effluent was graded with pressure. In Protocol 2, [ATP]v increased in each condition compared with rest (RFC: 123 ± 33; RHG: 51 ± 9; RFC + RHG: 96 ± 23 vs. Mean Rest: 42 ± 4 nmol/l; P < 0.05), and ATP effluent was greatest with RFC + RHG (RFC: 5.3 ± 1.4; RHG: 5.3 ± 1.1; RFC + RHG: 11.6 ± 2.7 vs. Mean Rest: 1.2 ± 0.1 nmol/min; P < 0.05). We conclude that the mechanical effects of muscle contraction can 1) independently elevate intravascular ATP draining quiescent skeletal muscle without changes in local metabolism and 2) further augment intravascular ATP during mild exercise associated with increases in metabolism and local deoxygenation; therefore, it is likely one stimulus for increasing intravascular ATP during exercise in humans.

DECREASED PHYSICAL ACTIVITY BLUNTS ACETYLCHOLINE-INDUCED INCREASES IN RAT SKELETAL MUSCLE BLOOD FLOW

1998 ◽  
Vol 30 (Supplement) ◽  
pp. 105
Author(s):  
W. G. Schrage ◽  
C. A. Ray ◽  
S. A. Friskey ◽  
E. M. Hasser ◽  
M. H. Laughlin
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Muscle Blood Flow ◽  
Rat Skeletal Muscle ◽  
Skeletal Muscle Blood Flow

Two weeks of muscle immobilization impairs functional sympatholysis but increases exercise hyperemia and the vasodilatory responsiveness to infused ATP

2012 ◽  
Vol 302 (10) ◽  
pp. H2074-H2082 ◽  
Author(s):  
S. P. Mortensen ◽  
J. Mørkeberg ◽  
P. Thaning ◽  
Y. Hellsten ◽  
B. Saltin
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Blood Pressure Response ◽  
Muscle Blood Flow ◽  
Knee Extensor ◽  
Training Status ◽  
Exercise Hyperemia ◽  
Functional Sympatholysis ◽  
Before And After ◽  
Response To Exercise

During exercise, contracting muscles can override sympathetic vasoconstrictor activity (functional sympatholysis). ATP and adenosine have been proposed to play a role in skeletal muscle blood flow regulation. However, little is known about the role of muscle training status on functional sympatholysis and ATP- and adenosine-induced vasodilation. Eight male subjects (22 ± 2 yr, V̇o2max: 49 ± 2 ml O2·min−1·kg−1) were studied before and after 5 wk of one-legged knee-extensor training (3–4 times/wk) and 2 wk of immobilization of the other leg. Leg hemodynamics were measured at rest, during exercise (24 ± 4 watts), and during arterial ATP (0.94 ± 0.03 μmol/min) and adenosine (5.61 ± 0.03 μmol/min) infusion with and without coinfusion of tyramine (11.11 μmol/min). During exercise, leg blood flow (LBF) was lower in the trained leg (2.5 ± 0.1 l/min) compared with the control leg (2.6 ± 0.2 l/min; P < 0.05), and it was higher in the immobilized leg (2.9 ± 0.2 l/min; P < 0.05). Tyramine infusion lowers LBF similarly at rest, but, when tyramine was infused during exercise, LBF was blunted in the immobilized leg (2.5 ± 0.2 l/min; P < 0.05), whereas it was unchanged in the control and trained leg. Mean arterial pressure was lower during exercise with the trained leg compared with the immobilized leg ( P < 0.05), and leg vascular conductance was similar. During ATP infusion, the LBF response was higher after immobilization (3.9 ± 0.3 and 4.5 ± 0.6 l/min in the control and immobilized leg, respectively; P < 0.05), whereas it did not change after training. When tyramine was coinfused with ATP, LBF was reduced in the immobilized leg ( P < 0.05) but remained similar in the control and trained leg. Training increased skeletal muscle P2Y2 receptor content ( P < 0.05), whereas it did not change with immobilization. These results suggest that muscle inactivity impairs functional sympatholysis and that the magnitude of hyperemia and blood pressure response to exercise is dependent on the training status of the muscle. Immobilization also increases the vasodilatory response to infused ATP.

Role of adenosine in regulating the heterogeneity of skeletal muscle blood flow during exercise in humans

2007 ◽  
Vol 103 (6) ◽  
pp. 2042-2048 ◽  
Author(s):  
Ilkka Heinonen ◽  
Sergey V. Nesterov ◽  
Jukka Kemppainen ◽  
Pirjo Nuutila ◽  
Juhani Knuuti ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Adenosine Receptor ◽  
Muscle Blood Flow ◽  
Isometric Exercise ◽  
Knee Extension ◽  
Receptor Blockade ◽  
Mean Values ◽  
Positron Emission ◽  
Exercise Hyperemia

Evidence from both animal and human studies suggests that adenosine plays a role in the regulation of exercise hyperemia in skeletal muscle. We tested whether adenosine also plays a role in the regulation of blood flow (BF) distribution and heterogeneity among and within quadriceps femoris (QF) muscles during exercise, measured using positron emission tomography. In six healthy young women, BF was measured at rest and then during three incremental low and moderate intermittent isometric one-legged knee-extension exercise intensities without and with theophylline-induced nonselective adenosine receptor blockade. BF heterogeneity within muscles was calculated from 16-mm3 voxels in BF images and heterogeneity among the muscles from the mean values of the four QF compartments. Mean BF in the whole QF and its four parts increased, and heterogeneity decreased with workload both without and with theophylline ( P < 0.001). Adenosine receptor blockade did not have any effect on mean bulk BF or BF heterogeneity among the QF muscles, yet blockade increased within-muscle BF heterogeneity in all four QF muscles ( P = 0.03). Taken together, these results show that BF becomes less heterogeneous with increasing exercise intensity in the QF muscle group. Adenosine seems to play a role in muscle BF heterogeneity even in the absence of changes in bulk BF at low and moderate one-leg intermittent isometric exercise intensities.

scholarly journals Hyperbaric hyperoxia reduces exercising forearm blood flow in humans

2011 ◽  
Vol 300 (5) ◽  
pp. H1892-H1897 ◽  
Author(s):  
Darren P. Casey ◽  
Michael J. Joyner ◽  
Paul L. Claus ◽  
Timothy B. Curry
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Forearm Blood Flow ◽  
Muscle Blood Flow ◽  
Hyperbaric Hyperoxia ◽  
Exercise Hyperemia ◽  
Forearm Vascular Conductance ◽  
Forearm Exercise ◽  
The Impact ◽  
Hyperemic Response

Hypoxia during exercise augments blood flow in active muscles to maintain the delivery of O2 at normoxic levels. However, the impact of hyperoxia on skeletal muscle blood flow during exercise is not completely understood. Therefore, we tested the hypothesis that the hyperemic response to forearm exercise during hyperbaric hyperoxia would be blunted compared with exercise during normoxia. Seven subjects (6 men/1 woman; 25 ± 1 yr) performed forearm exercise (20% of maximum) under normoxic and hyperoxic conditions. Forearm blood flow (FBF; in ml/min) was measured using Doppler ultrasound. Forearm vascular conductance (FVC; in ml·min−1·100 mmHg−1) was calculated from FBF and blood pressure (in mmHg; brachial arterial catheter). Studies were performed in a hyperbaric chamber with the subjects supine at 1 atmospheres absolute (ATA) (sea level) while breathing normoxic gas [21% O2, 1 ATA; inspired Po2 (PiO2) ≈ 150 mmHg] and at 2.82 ATA while breathing hyperbaric normoxic (7.4% O2, 2.82 ATA, PiO2 ≈ 150 mmHg) and hyperoxic (100% O2, 2.82 ATA, PiO2 ≈ 2,100 mmHg) gas. Resting FBF and FVC were less during hyperbaric hyperoxia compared with hyperbaric normoxia ( P < 0.05). The change in FBF and FVC (Δ from rest) during exercise under normoxia (204 ± 29 ml/min and 229 ± 37 ml·min−1·100 mmHg−1, respectively) and hyperbaric normoxia (203 ± 28 ml/min and 217 ± 35 ml·min−1·100 mmHg−1, respectively) did not differ ( P = 0.66–0.99). However, the ΔFBF (166 ± 21 ml/min) and ΔFVC (163 ± 23 ml·min−1·100 mmHg−1) during hyperbaric hyperoxia were substantially attenuated compared with other conditions ( P < 0.01). Our data suggest that exercise hyperemia in skeletal muscle is highly dependent on oxygen availability during hyperoxia.

scholarly journals Effect of rhythmic tetanic skeletal muscle contractions on peak muscle perfusion

2003 ◽  
Vol 94 (1) ◽  
pp. 11-19 ◽  
Author(s):  
John L. Dobson ◽  
L. Bruce Gladden
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Popliteal Artery ◽  
Muscle Blood Flow ◽  
Venous Pressure ◽  
Mechanical Action ◽  
Muscle Contractions ◽  
Primary Role ◽  
Muscle Perfusion ◽  
In Series

The purpose of this investigation was to examine the effect of rhythmic tetanic skeletal muscle contractions on peak muscle perfusion by using spontaneously perfused canine gastrocnemii in situ. Simultaneous pulsatile blood pressures were measured by means of transducers placed in the popliteal artery and vein, and pulsatile flow was measured with a flow-through-type transit-time ultrasound probe placed in the venous return line. Two series of experiments were performed. In series 1, maximal vasodilation of the muscles' vascular beds was elicited by infusing a normal saline solution containing adenosine (29.3 mg/min) and sodium nitroprusside (180 μg/min) for 15 s and then simultaneously occluding both the popliteal artery and vein for 5 min. The release of occlusion initiated a maximal hyperemic response, during which time four tetanic contractions were induced with supramaximal voltage (6–8 V, 0.2-ms stimuli for 200-ms duration at 50 Hz, 1/s). In series 2, the muscles were stimulated for 3 min before the muscle contractions were stopped for a period of 3 s; stimulation was then resumed. The results of series 1 indicate that, although contractions lowered venous pressure, muscle blood flow was significantly reduced from 2,056 ± 246 to 1,738 ± 225 ml · kg−1 · min−1when contractions were initiated and then increased significantly to 1,925 ± 225 ml · kg−1 · min−1during the first 5 s after contractions were stopped. In series 2, blood flow after 3 min of contractions averaged 1,454 ± 149 ml · kg−1 · min−1. Stopping the contractions for 3 s caused blood flow to increase significantly to 1,874 ± 172 ml · kg−1 · min−1; blood flow declined significantly to 1,458 ± 139 ml · kg−1 · min−1when contractions were resumed. We conclude that the mechanical action of rhythmic, synchronous, maximal isometric tetanic skeletal muscle contractions inhibits peak muscle perfusion during maximal and near-maximal vasodilation of the muscle's vascular bed. This argues against a primary role for the muscle pump in achieving peak skeletal muscle blood flow.

Neural control of glucose uptake by skeletal muscle after central administration of NMDA

1995 ◽  
Vol 268 (2) ◽  
pp. R492-R497 ◽  
Author(s):  
C. H. Lang ◽  
M. Ajmal ◽  
A. G. Baillie
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Neural Control ◽  
Plasma Insulin ◽  
Regional Blood Flow ◽  
Muscle Blood Flow ◽  
Whole Body ◽  
Glucose Disposal ◽  
Central Administration

Intracerebroventricular injection of N-methyl-D-aspartate (NMDA) produces hyperglycemia and increases whole body glucose uptake. The purpose of the present study was to determine in rats which tissues are responsible for the elevated rate of glucose disposal. NMDA was injected intracerebroventricularly, and the glucose metabolic rate (Rg) was determined for individual tissues 20-60 min later using 2-deoxy-D-[U-14C]glucose. NMDA decreased Rg in skin, ileum, lung, and liver (30-35%) compared with time-matched control animals. In contrast, Rg in skeletal muscle and heart was increased 150-160%. This increased Rg was not due to an elevation in plasma insulin concentrations. In subsequent studies, the sciatic nerve in one leg was cut 4 h before injection of NMDA. NMDA increased Rg in the gastrocnemius (149%) and soleus (220%) in the innervated leg. However, Rg was not increased after NMDA in contralateral muscles from the denervated limb. Data from a third series of experiments indicated that the NMDA-induced increase in Rg by innervated muscle and its abolition in the denervated muscle were not due to changes in muscle blood flow. The results of the present study indicate that 1) central administration of NMDA increases whole body glucose uptake by preferentially stimulating glucose uptake by skeletal muscle, and 2) the enhanced glucose uptake by muscle is neurally mediated and independent of changes in either the plasma insulin concentration or regional blood flow.

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