Role of nitric oxide in skeletal muscle blood flow at rest and during dynamic exercise in humans

1997 ◽  
Vol 273 (1) ◽  
pp. H405-H410 ◽  
Author(s):  
R. C. Hickner ◽  
J. S. Fisher ◽  
A. A. Ehsani ◽  
W. M. Kohrt
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Vastus Lateralis ◽  
Muscle Blood Flow ◽  
Dynamic Exercise ◽  
Skeletal Muscle Blood Flow ◽  
Blood Flows ◽  
And Control

The role of nitric oxide at rest and in the active hyperemic response within skeletal muscle was investigated in eight physically active men. Three microdialysis probes were inserted into the vastus lateralis of the quadriceps femoris muscle group in each subject. Microdialysis probes were perfused with a Ringer solution containing 5.0 mM ethanol, 2.5 mM glucose, and either 10 mg/ml of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) monoacetate salt, 30 mg/ml of the nitric oxide precursor L-arginine, or no additional substance (control probe). Subjects performed one-legged cycling exercise at work rates ranging from 25 to 100 W. Dialysate and perfusate ethanol concentrations were presented as the ratio of [ethanol]dialysate to [ethanol]perfusate (ethanol outflow-to-inflow ratio), an indicator that is inversely related to blood flow. The ethanol outflow-to-inflow ratios at rest were 0.614 +/- 0.032, 0.523 +/- 0.023, and 0.578 +/- 0.039 in the L-NMMA, L-arginine, and control probes, respectively. Calculated resting blood flows were therefore 8.7 +/- 4.1, 20.5 +/- 4.6, and 14.0 +/- 4.7 ml.min-1.100 g-1 around the L-NMMA, L-arginine, and control probes, respectively. The ethanol outflow-to-inflow ratios were significantly higher at all exercise intensities in the L-NMMA probe than in the control and L-arginine probes, resulting in calculated blood flows of 195 +/- 55, 407 +/- 47, and 352 +/- 60 ml.min-1.100 g-1 at 25 W and 268 +/- 65, 602 +/- 129, and 519 +/- 113 ml.min-1.100 g-1 at 100 W around the L-NMMA, L-arginine, and control probes, respectively. Skeletal muscle blood flow was therefore reduced both at rest and during continuous, dynamic exercise by the action of L-NMMA, whereas blood flow was increased only at rest by L-arginine.

Nitric oxide and prostaglandins influence local skeletal muscle blood flow during exercise in humans: coupling between local substrate uptake and blood flow

2006 ◽  
Vol 291 (3) ◽  
pp. R803-R809 ◽  
Author(s):  
Kari K. Kalliokoski ◽  
Henning Langberg ◽  
Ann Kathrine Ryberg ◽  
Celena Scheede-Bergdahl ◽  
Simon Doessing ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Vastus Lateralis ◽  
Muscle Blood Flow ◽  
Vastus Lateralis Muscle ◽  
Substrate Uptake ◽  
Skeletal Muscle Blood Flow ◽  
Lateralis Muscle

Synergic action of nitric oxide (NO) and prostaglandins (PG) in the regulation of muscle blood flow during exercise has been demonstrated. In the present study, we investigated whether these vasodilators also regulate local blood flow, flow heterogeneity, and glucose uptake within the exercising skeletal muscle. Skeletal muscle blood flow was measured in seven healthy young men using near-infrared spectroscopy and indocyanine green and muscle glucose uptake using positron emission tomography and 2-fluoro-2-deoxy-d-[18F]glucose without and with local blockade of NO and PG at rest and during one-legged dynamic knee-extension exercise. Local blockade was produced by infusing nitro-l-arginine methyl ester and indomethacin directly in the muscle via a microdialysis catheter. Blood flow and glucose uptake were measured in the region of blockade and in two additional regions of vastus lateralis muscle 1 and 4 cm away from the infusion of blockers. Local blockade during exercise at 25 and 40 watts significantly decreased blood flow in the infusion region and in the region 1 cm away from the site of infusion but not in the region 4 cm away. During exercise, muscle glucose uptake did not show any regional differences in response to blockade. These results show that NO and PG synergistically contribute to the local regulation of blood flow in skeletal muscle independently of muscle glucose uptake in healthy young men. Thus these vasodilators can play a role in regulating microvascular blood flow in localized regions of vastus lateralis muscle but do not influence regional glucose uptake. The findings suggest that local substrate uptake in skeletal muscle can be regulated independently of regional changes in blood flow.

Skeletal muscle blood flow and flow heterogeneity during dynamic and isometric exercise in humans

2003 ◽  
Vol 284 (3) ◽  
pp. H979-H986 ◽  
Author(s):  
Marko S. Laaksonen ◽  
Kari K. Kalliokoski ◽  
Heikki Kyröläinen ◽  
Jukka Kemppainen ◽  
Mika Teräs ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Vastus Lateralis ◽  
Muscle Blood Flow ◽  
Isometric Exercise ◽  
Dynamic Exercise ◽  
Emg Activity ◽  
Vastus Lateralis Muscle ◽  
Skeletal Muscle Blood Flow ◽  
Flow Heterogeneity

The effects of dynamic and intermittent isometric knee extension exercises on skeletal muscle blood flow and flow heterogeneity were studied in seven healthy endurance-trained men. Regional muscle blood flow was measured using positron emission tomography (PET) and an [15O]H2O tracer, and electromyographic (EMG) activity was recorded in the quadriceps femoris (QF) muscle during submaximal intermittent isometric and dynamic exercises. QF blood flow was 61% ( P = 0.002) higher during dynamic exercise. Interestingly, flow heterogeneity was 13% ( P = 0.024) lower during dynamic compared with intermittent isometric exercise. EMG activity was significantly higher ( P < 0.001) during dynamic exercise, and the change in EMG activity from isometric to dynamic exercise was tightly related to the change in blood flow in the vastus lateralis muscle ( r = 0.98, P < 0.001) but not in the rectus femoris muscle ( r = −0.09, P = 0.942). In conclusion, dynamic exercise causes higher and less heterogeneous blood flow than intermittent isometric exercise at the same exercise intensity. These responses are, at least partly, related to the increased EMG activity.

Biphasic effect of hydrogen peroxide on skeletal muscle arteriolar tone via activation of endothelial and smooth muscle signaling pathways

2004 ◽  
Vol 97 (3) ◽  
pp. 1130-1137 ◽  
Author(s):  
Csongor Csekő ◽  
Zsolt Bagi ◽  
Akos Koller
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Hydrogen Peroxide ◽  
Blood Flow ◽  
Smooth Muscle ◽  
Muscle Blood Flow ◽  
Skeletal Muscle Blood Flow ◽  
Local Regulation ◽  
Prostaglandin H ◽  
Arteriolar Tone

We hypothesized that hydrogen peroxide (H2O2) has a role in the local regulation of skeletal muscle blood flow, thus significantly affecting the myogenic tone of arterioles. In our study, we investigated the effects of exogenous H2O2 on the diameter of isolated, pressurized (at 80 mmHg) rat gracilis skeletal muscle arterioles (diameter of ∼150 μm). Lower concentrations of H2O2 (10−6–3 × 10−5 M) elicited constrictions, whereas higher concentrations of H2O2 (6 × 10−5–3 × 10−4 M), after initial constrictions, caused dilations of arterioles (at 10−4 M H2O2, −19 ± 1% constriction and 66 ± 4% dilation). Endothelium removal reduced both constrictions (to −10 ± 1%) and dilations (to 33 ± 3%) due to H2O2. Constrictions due to H2O2 were completely abolished by indomethacin and the prostaglandin H2/thromboxane A2 (PGH2/TxA2) receptor antagonist SQ-29548. Dilations due to H2O2 were significantly reduced by inhibition of nitric oxide synthase (to 38 ± 7%) but were unaffected by clotrimazole or sulfaphenazole (inhibitors of cytochrome P-450 enzymes), indomethacin, or SQ-29548. In endothelium-denuded arterioles, clotrimazole had no effect, whereas H2O2-induced dilations were significantly reduced by charybdotoxin plus apamin, inhibitors of Ca2+-activated K+ channels (to 24 ± 3%), the selective blocker of ATP-sensitive K+ channels glybenclamide (to 14 ± 2%), and the nonselective K+-channel inhibitor tetrabutylammonium (to −1 ± 1%). Thus exogenous administration of H2O2 elicits 1) release of PGH2/TxA2 from both endothelium and smooth muscle, 2) release of nitric oxide from the endothelium, and 3) activation of K+ channels, such as Ca2+-activated and ATP-sensitive K+ channels in the smooth muscle resulting in biphasic changes of arteriolar diameter. Because H2O2 at low micromolar concentrations activates several intrinsic mechanisms, we suggest that H2O2 contributes to the local regulation of skeletal muscle blood flow in various physiological and pathophysiological conditions.

Muscle blood flow during exercise in sedentary and trained hypothyroid rats

1995 ◽  
Vol 269 (6) ◽  
pp. H1949-H1954 ◽  
Author(s):  
R. M. McAllister ◽  
M. D. Delp ◽  
K. A. Thayer ◽  
M. H. Laughlin
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Muscle Blood Flow ◽  
Treadmill Running ◽  
Exercise Intolerance ◽  
Vastus Lateralis Muscle ◽  
Blood Flows ◽  
Vastus Intermedius

Hypothyroidism is characterized by exercise intolerance. We hypothesized that active muscle blood flow during in vivo exercise is inadequate in the hypothyroid state. Additionally, we hypothesized that endurance exercise training would restore normal blood flow during acute exercise. To test these hypotheses, rats were made hypothyroid (Hypo) over 3-4 mo with propylthiouracil. A subset of Hypo rats was trained (THypo) on a treadmill at 30 m/min (15% grade) for 60 min/day 5 days/wk over 10-15 wk. Hypothyroidism was evidenced by approximately 80% reductions in plasma triiodothyronine levels in Hypo and THypo and by 40-50% reductions in citrate synthase activities in high oxidative muscles in Hypo compared with euthyroid (Eut) rats. Training efficacy was indicated by increased (25-100%) citrate synthase activities in muscles of THypo vs. Hypo. Regional blood flows were determined by the radiolabeled microsphere method before exercise and at 1-2 min of treadmill running at 15 m/min (0% grade). Preexercise muscle blood flows were generally similar among groups. During exercise, however, flows were lower in Hypo than in Eut for high oxidative muscles such as the red section of vastus lateralis [277 +/- 24 and 153 +/- 13 (SE) ml.min-1.100 g-1 for Eut and Hypo, respectively; P < 0.01] and vastus intermedius (317 +/- 32 and 187 +/- 20 ml.min-1.100 g-1 for Eut and Hypo, respectively; P < 0.01) muscles. Training (THypo) did not normalize these flows (168 +/- 24 and 181 +/- 24 ml.min-1.100 g-1 for red section of vastus lateralis and vastus intermedius muscles, respectively). Blood flows to low oxidative muscle, such as the white section of vastus lateralis muscle, were similar among groups (21 +/- 5, 25 +/- 4, and 34 +/- 7 ml.min-1.100 g-1 for Eut, Hypo, and THypo, respectively; P = NS). These findings indicate that hypothyroidism is associated with reduced blood flow to skeletal muscle during exercise, suggesting that impaired delivery of nutrients to and/or removal of metabolites from skeletal muscle contributes to the poor exercise tolerance characteristic of hypothyroidism.

ATP-induced vasodilation and purinergic receptors in the human leg: roles of nitric oxide, prostaglandins, and adenosine

2009 ◽  
Vol 296 (4) ◽  
pp. R1140-R1148 ◽  
Author(s):  
Stefan P. Mortensen ◽  
José González-Alonso ◽  
Laurids T. Bune ◽  
Bengt Saltin ◽  
Henriette Pilegaard ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Human Skeletal Muscle ◽  
Purinergic Receptors ◽  
Vastus Lateralis ◽  
Muscle Blood Flow ◽  
Pcr Analysis ◽  
Receptor Subtypes ◽  
Vastus Lateralis Muscle

Plasma ATP is thought to contribute to the local regulation of skeletal muscle blood flow. Intravascular ATP infusion can induce profound limb muscle vasodilatation, but the purinergic receptors and downstream signals involved in this response remain unclear. This study investigated: 1) the role of nitric oxide (NO), prostaglandins, and adenosine as mediators of ATP-induced limb vasodilation and 2) the expression and distribution of purinergic P2 receptors in human skeletal muscle. Systemic and leg hemodynamics were measured before and during 5–7 min of femoral intra-arterial infusion of ATP [0.45–2.45 μmol/min] in 19 healthy male subjects with and without coinfusion of NG-monomethyl-l-arginine (l-NMMA; NO formation inhibitor; 12.3 ± 0.3 (SE) mg/min), indomethacin (INDO; prostaglandin formation blocker; 613 ± 12 μg/min), and/or theophylline (adenosine receptor blocker; 400 ± 26 mg). During control conditions, ATP infusion increased leg blood flow (LBF) from baseline conditions by 1.82 ± 0.14 l/min. When ATP was coinfused with either l-NMMA, INDO, or l-NMMA + INDO combined, the increase in LBF was reduced by 14 ± 6, 15 ± 9, and 39 ± 8%, respectively (all P < 0.05), and was associated with a parallel lowering in leg vascular conductance and cardiac output and a compensatory increase in leg O2 extraction. Infusion of theophylline did not alter the ATP-induced leg hyperemia or systemic variables. Real-time PCR analysis of the mRNA content from the vastus lateralis muscle of eight subjects showed the highest expression of P2Y2 receptors of the 10 investigated P2 receptor subtypes. Immunohistochemistry showed that P2Y2 receptors were located in the endothelium of microvessels and smooth muscle cells, whereas P2X1 receptors were located in the endothelium and the sacrolemma. Collectively, these results indicate that NO and prostaglandins, but not adenosine, play a role in ATP-induced vasodilation in human skeletal muscle. The expression and localization of the nucleotide selective P2Y2 and P2X1 receptors suggest that these receptors may mediate ATP-induced vasodilation in skeletal muscle.

Regional blood flows in salt loading hypertension in the dog

1981 ◽  
Vol 240 (3) ◽  
pp. H361-H367 ◽  
Author(s):  
J. F. Liard
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Cardiac Output ◽  
Arterial Pressure ◽  
Muscle Blood Flow ◽  
Peripheral Resistance ◽  
Salt Loading ◽  
Skeletal Muscle Blood Flow ◽  
Blood Flows ◽  
Regional Blood Flows

An intravenous infusion of isotonic sodium chloride, 196 ml/kg per day, was administered for several days to eight dogs with their renal mass reduced. Mean arterial pressure, cardiac output (electromagnetic flowmeter), and regional blood flows (radioactive microspheres) were measured sequentially and the results compared with those obtained in six control dogs. The salt-loaded animals exhibited on the 1st day of the infusion a 25% increase of arterial pressure and cardiac output. Blood flows to the kidney, the splanchnic area, the skin, and the bone were not significantly changed, whereas skeletal muscle blood flow almost doubled. After several days, cardiac output returned toward control values but pressure remained elevated. Skeletal muscle blood flow, as most other regional flows, did not differ significantly from control values at that time. In four dogs studied 6 h after starting a faster saline infusion, most of the increase in cardiac output was also distributed to the skeletal muscle. Total peripheral resistance changes did not reflect the resistance of individual beds, because vasoconstriction appeared early in some areas but was masked by prominent, although transient, vasodilation in skeletal muscle.

Sign in / Sign up

Export Citation Format

Share Document