doppler-ultrasound-based-leg-blood-flow-assessment-during-single-leg

Doppler Ultrasound-Based Leg Blood Flow Assessment During Single-Leg Knee-Extensor Exercise in an Uncontrolled Setting

Doppler ultrasound has revolutionized the assessment of organ blood flow and is widely used in research and clinical settings. While Doppler ...

Integrated Physiology Group

In animal studies, the polyphenol resveratrol has been shown to influence several pathways of importance for angiogenesis in skeletal muscle. The aim of the present study was to examine the angiogenic effect of resveratrol supplementation with parallel exercise training in aged men. Forty-three healthy physically inactive aged men (65 ± 1 yr) were divided into 1) a training group that conducted 8 wk of intense exercise training where half of the subjects received a daily intake of either 250 mg trans-resveratrol (n = 14) and the other half received placebo (n = 13) and 2) a nontraining group that received either 250 mg trans-resveratrol (n = 9) or placebo (n = 7). The group that trained with placebo showed a ~20% increase in the capillary-to-fiber ratio, an increase in muscle protein expression of VEGF, VEGF receptor-2, and tissue inhibitor of matrix metalloproteinase (TIMP-1) but unaltered thrombospodin-1 levels. Muscle interstitial VEGF and thrombospodin-1 protein levels were unchanged after the training period. The group that trained with resveratrol supplementation did not show an increase in the capillary-to-fiber ratio or an increase in muscle VEGF protein. Muscle TIMP-1 protein levels were lower in the training and resveratrol group than in the training and placebo group. Both training groups showed an increase in forkhead box O1 protein. In nontraining groups, TIMP-1 protein was lower in the resveratrol-treated group than the placebo-treated group after 8 wk. In conclusion, these data show that exercise training has a strong angiogenic effect, whereas resveratrol supplementation may limit basal and training-induced angiogenesis.

Resveratrol modulates the angiogenic response to exercise training in skeletal muscles of aged men.

Training for skeletal muscle capillarization: a Janus-faced role of exercise intensity?

What are the chances that resveratrol will be the drug of tomorrow?

Aging impairs vascular function in women, with the largest detrimental effects occurring during the menopausal transition. Deficiency in the nitric oxide system has been suggested to be responsible for impairment in vascular function with aging, but recent observations suggest that the prostacyclin system, acting in redundancy with the nitric oxide system, may be of importance too. Improvement in vascular function is a hallmark of exercise training and we hypothesize that leg vascular function is improved by exercise training in late postmenopausal women, and that the underlying mechanism is increased endothelial formation of prostacyclin and responsiveness to prostacyclin by the vascular smooth muscle cells.

Increased prostacyclin formation after high-intensity interval training in late postmenopausal women.

The influence of glucose and palmitic acid (PA) on mitochondrial respiration and emission of hydrogen peroxide (H O ) was determined in skeletal muscle-derived microvascular endothelial cells. Measurements were assessed in intact and permeabilized (cells treated with 0.025% saponin) low passage endothelial cells with acute-or prolonged (3 days) incubation with regular (1.7 mM) or elevated (2.2 mM) PA concentrations and regular (5 mM) or elevated (11 mM) glucose concentrations. In intact cells, acute incubation with 1.7 mM PA alone or with 1.7 mM PA + 5 mM glucose (p < .001) led to a lower mitochondrial respiration (p < 0.01) and markedly higher H O /O emission (p < 0.05) than with 5 mM glucose alone. Prolonged incubation of intact cells with 1.7 mM PA +5 mM glucose led to 34% (p < 0.05) lower respiration and 2.5-fold higher H O /O emission (p < 0.01) than incubation with 5 mM glucose alone. Prolonged incubation of intact cells with elevated glucose led to 60% lower (p < 0.05) mitochondrial respiration and 4.6-fold higher H O /O production than incubation with 5 mM glucose in intact cells (p < 0.001). All effects observed in intact cells were present also in permeabilized cells (State 2). In conclusion, our results show that acute and prolonged lipid availability, as well as prolonged hyperglycemia, induces mitochondrial dysfunction as evidenced by lower mitochondrial respiration and enhanced H O O emission. Elevated plasma substrate availability may lead to microvascular dysfunction in skeletal muscle by impairing endothelial mitochondrial function.

High metabolic substrate load induces mitochondrial dysfunction in rat skeletal muscle microvascular endothelial cells.

Aerobic training can improve vascular endothelial function in-vivo. The aim of this study was to elucidate the mechanisms underlying this improvement in isolated human microvascular endothelial cells. Sedentary males, aged 57 ± 6 years completed 8 weeks of intense aerobic training. Resting muscle biopsies were obtained from the thigh muscle and used for isolation of endothelial cells (pre n = 23, post n = 16). The cells were analyzed for mitochondrial respiration, HO emission, glycolysis, protein levels of antioxidants, NADPH oxidase, endothelial nitric oxide (NO) synthase and prostacyclin synthase (PGIS). In-vivo microvascular function, assessed by acetylcholine infusion and arterial blood pressure were also determined. Endothelial mitochondrial respiration and HO formation were similar before and after training whereas the expression of superoxide dismutase and the expression of glutathione peroxidase were 2.4-fold (p = 0.012) and 2.3-fold (p = 0.006) higher, respectively, after training. In-vivo microvascular function was increased by 1.4-fold (p = 0.036) in parallel with a 2.1-fold increase in endothelial PGIS expression (p = 0.041). Endothelial cell glycolysis was reduced after training, as indicated by a 65% lower basal production of lactate (p = 0.003) and a 30% lower expression of phosphofructokinase (p = 0.011). Subdivision of the participants according to blood pressure at base-line (n = 23), revealed a 2-fold higher (p = 0.049) rate of HO production in endothelial cells from hypertensive participants. Our data show that exercise training increases skeletal muscle microvascular endothelial cell metabolism, antioxidant capacity and the capacity to form prostacyclin. Moreover, elevated blood pressure is associated with increased endothelial mitochondrial ROS formation.

Article	Year
Resveratrol modulates the angiogenic response to exercise training in skeletal muscles of aged men. American journal of physiology. Heart and circulatory physiology\| PubMed ID: 25128170	2014
Training for skeletal muscle capillarization: a Janus-faced role of exercise intensity? European journal of applied physiology\| PubMed ID: 27342704	2016
What are the chances that resveratrol will be the drug of tomorrow? Pharmacological research\| PubMed ID: 29425727	2018
Increased prostacyclin formation after high-intensity interval training in late postmenopausal women. European journal of applied physiology\| PubMed ID: 32474682	2020
High metabolic substrate load induces mitochondrial dysfunction in rat skeletal muscle microvascular endothelial cells. Physiological reports\| PubMed ID: 34288561	2021
Redox balance in human skeletal muscle-derived endothelial cells - Effect of exercise training. Free radical biology & medicine\| PubMed ID: 34954023	2022

Lasse Gliemann

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