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.

scholarly journals Combined inhibition of nitric oxide and prostaglandins reduces human skeletal muscle blood flow during exercise

2002 ◽  
Vol 543 (2) ◽  
pp. 691-698 ◽  
Author(s):  
Robert Boushel ◽  
Henning Langberg ◽  
Carsten Gemmer ◽  
Jens Olesen ◽  
Regina Crameri ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Human Skeletal Muscle ◽  
Muscle Blood Flow ◽  
Skeletal Muscle Blood Flow

scholarly journals Sex differences with aging in nutritive skeletal muscle blood flow: impact of exercise training, nitric oxide, and α-adrenergic-mediated mechanisms

2014 ◽  
Vol 307 (4) ◽  
pp. H524-H532 ◽  
Author(s):  
Justin D. La Favor ◽  
Raymond M. Kraus ◽  
Jonathan A. Carrithers ◽  
Steven L. Roseno ◽  
Timothy P. Gavin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Exercise Training ◽  
Healthy Aging ◽  
Muscle Blood Flow ◽  
Young Men ◽  
Men And Women ◽  
Skeletal Muscle Blood Flow ◽  
Age Related

The incidence of cardiovascular disease increases progressively with age, but aging may affect men and women differently. Age-associated changes in vascular structure and function may manifest in impaired nutritive blood flow, although the regulation of nutritive blood flow in healthy aging is not well understood. The purpose of this study was to determine if nitric oxide (NO)-mediated or α-adrenergic-mediated regulation of nutritive skeletal muscle blood flow is impaired with advanced age, and if exercise training improves age-related deficiencies. Nutritive blood flow was monitored in the vastus lateralis of healthy young and aged men and women via the microdialysis-ethanol technique prior to and following seven consecutive days of exercise training. NO-mediated and α-adrenergic-mediated regulation of nutritive blood flow was assessed by microdialysis perfusion of acetylcholine, sodium nitroprusside, NG-monomethyl-l-arginine, norepinephrine, or phentolamine. Pretraining nutritive blood flow was attenuated in aged compared with young women (7.39 ± 1.5 vs. 15.5 ± 1.9 ml·100 g−1·min−1, P = 0.018), but not aged men (aged 13.5 ± 3.7 vs. young 9.4 ± 1.3 ml·100 g−1·min−1, P = 0.747). There were no age-associated differences in NO-mediated or α-adrenergic-mediated nutritive blood flow. Exercise training increased resting nutritive blood flow only in young men (9.4 ± 1.3 vs. 19.7 ml·100 g−1·min−1, P = 0.005). The vasodilatory effect of phentolamine was significantly reduced following exercise training only in young men (12.3 ± 6.14 vs. −3.68 ± 3.26 ml·100 g−1·min−1, P = 0.048). In conclusion, the age-associated attenuation of resting nutritive skeletal muscle blood flow was specific to women, while the exercise-induced alleviation of α-adrenergic mediated vasoconstriction that was specific to young men suggests an age-associated modulation of the sympathetic response to exercise training.

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.

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.

Systemic Nitric Oxide Synthase Inhibition Increases Insulin Sensitivity in Man

1998 ◽  
Vol 94 (2) ◽  
pp. 175-180 ◽  
Author(s):  
R. Butler ◽  
A.D. Morris ◽  
A. D. Struthers
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Insulin Sensitivity ◽  
Nitric Oxide Synthase ◽  
Glucose Uptake ◽  
Muscle Blood Flow ◽  
Whole Body ◽  
Skeletal Muscle Blood Flow ◽  
Oxide Synthase

1. Recent evidence shows that skeletal muscle blood flow is an important determinant of insulin sensitivity and that insulin-mediated vasodilatation is nitric oxide dependent. These results have given rise to the hypothesis that endothelial nitric oxide inhibition may decrease insulin sensitivity in humans. 2. We examined this hypothesis directly by evaluating the effects of systemic nitric oxide synthase inhibition with NG-monomethyl l-arginine (3 mg h−1 kg−1) on whole-body glucose uptake (euglycaemic hyperinsulinaemic clamp) and calf blood flow (bilateral calf venous occlusion plethysmography) in 16 healthy male subjects in a randomized, double-blind, placebo-controlled, crossover study. 3. NG-Monomethyl l-arginine infusion was associated with a pressor effect (119/61 ± 2/2 compared with 114/58 ± 2/2 mmHg for placebo; P < 0.001), and a negative chronotropic response (57 ± 2 compared with 62 ± 2 beats/min for placebo; P < 0.001). The glucose infusion rate was significantly increased after infusion of NG-monomethyl l-arginine (8.9 ± 0.9 compared with 7.9 ± 0.8 mg min−1 kg−1 for placebo; P = 0.002). Whole-body glucose uptake increased during the clamp, with values of 9.4 ± 0.7 and 10.9 ± 0.8 mg min−1 kg−1 for placebo and NG-monomethyl l-arginine respectively (P = 0.036; 95% confidence interval 0.2,2.8). NG-Monomethyl l-arginine was associated with increased calf blood flow by comparison with placebo (P < 0.05, area under curve). 4. These data show for the first time that systemic inhibition of nitric oxide synthesis increases rather than decreases whole-body glucose uptake. We suggest that the higher skeletal muscle blood flow seen after NG-monomethyl l-arginine may explain the observed increase in whole-body glucose uptake.

Skeletal muscle blood flow and oxygen uptake at rest and during exercise in humans: a pet study with nitric oxide and cyclooxygenase inhibition

2011 ◽  
Vol 300 (4) ◽  
pp. H1510-H1517 ◽  
Author(s):  
Heinonen Ilkka ◽  
Saltin Bengt ◽  
Kemppainen Jukka ◽  
Hannu T. Sipilä ◽  
Oikonen Vesa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Oxygen Uptake ◽  
Muscle Blood Flow ◽  
Arterial Infusion ◽  
Skeletal Muscle Blood Flow ◽  
Muscle Oxygen ◽  
Resting Muscle ◽  
Muscle Oxygen Uptake

The aim of the present study was to determine the effect of nitric oxide and prostanoids on microcirculation and oxygen uptake, specifically in the active skeletal muscle by use of positron emission tomography (PET). Healthy males performed three 5-min bouts of light knee-extensor exercise. Skeletal muscle blood flow and oxygen uptake were measured at rest and during the exercise using PET with H2O15 and 15O2 during: 1) control conditions; 2) nitric oxide synthase (NOS) inhibition by arterial infusion of NG-monomethyl-l-arginine (l-NMMA), and 3) combined NOS and cyclooxygenase (COX) inhibition by arterial infusion of l-NMMA and indomethacin. At rest, inhibition of NOS alone and in combination with indomethacin reduced ( P < 0.05) muscle blood flow. NOS inhibition increased ( P < 0.05) limb oxygen extraction fraction (OEF) more than the reduction in muscle blood flow, resulting in an ∼20% increase ( P < 0.05) in resting muscle oxygen consumption. During exercise, muscle blood flow and oxygen uptake were not altered with NOS inhibition, whereas muscle OEF was increased ( P < 0.05). NOS and COX inhibition reduced ( P < 0.05) blood flow in working quadriceps femoris muscle by 13%, whereas muscle OEF and oxygen uptake were enhanced by 51 and 30%, respectively. In conclusion, by specifically measuring blood flow and oxygen uptake by the use of PET instead of whole limb measurements, the present study shows for the first time in humans that inhibition of NO formation enhances resting muscle oxygen uptake and that combined inhibition of NOS and COX during exercise increases muscle oxygen uptake.

scholarly journals Is Sympathetic Restraint of Skeletal Muscle Blood Flow Present During Exercise?

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Zachary Barrett‐O'Keefe ◽  
Stephen J. Ives ◽  
Joel D. Trinity ◽  
Melissa A.H. Witman ◽  
Matthew J. Rossman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Muscle Blood Flow ◽  
Skeletal Muscle Blood Flow
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