Insulin-mediated changes in leg blood flow are coupled to capillary density in skeletal muscle in healthy 70-year-old men

Metabolism ◽  
2001 ◽  
Vol 50 (9) ◽  
pp. 1078-1082 ◽  
Author(s):  
Anu Hedman ◽  
Per-Erik Andersson ◽  
Richard Reneland ◽  
Hans O. Lithell
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Capillary Density ◽  
Leg Blood Flow ◽  
Old Men

scholarly journals Mechanisms underlying absent training-induced improvement in insulin action in lean, hyperandrogenic women with polycystic ovary syndrome (PCOS)

2020 ◽  
Author(s):  
Ada Admin ◽  
Solvejg L. Hansen ◽  
Kirstine N. Bojsen-Møller ◽  
Anne-Marie Lundsgaard ◽  
Frederikke L. Hendrich ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Exercise Training ◽  
Polycystic Ovary Syndrome ◽  
Glucose Uptake ◽  
Insulin Action ◽  
Polycystic Ovary ◽  
Whole Body ◽  
Ovary Syndrome ◽  
Leg Blood Flow

Women with polycystic ovary syndrome (PCOS) have been shown to be less insulin sensitive compared with control women, independent of BMI. Training is associated with molecular adaptations in skeletal muscle improving glucose uptake and metabolism in both healthy and type 2 diabetic individuals. In the present study, lean, hyperandrogenic women with PCOS (n=9) and healthy controls (CON, n=9) completed 14 weeks of controlled and supervised exercise training. In CON, the training intervention increased whole body insulin action by 26% and insulin-stimulated leg glucose uptake by 53%, together with increased insulin-stimulated leg blood flow and a more oxidative muscle fiber type distribution. In PCOS, no such changes were found, despite similar training intensity and improvements in maximal oxygen uptake. In skeletal muscle of CON, but not PCOS, training increased GLUT4 and HKII mRNA and protein expressions. These data suggest that the impaired increase in whole body insulin action in women with PCOS with training is caused by an impaired ability to upregulate key glucose handling proteins for insulin-stimulated glucose uptake in skeletal muscle, and insulin-stimulated leg blood flow. Still, other important benefits of exercise training appeared in women with PCOS, including an improvement of the hyperandrogenic state.

Norepinephrine spillover from skeletal muscle during exercise in humans: role of muscle mass

1989 ◽  
Vol 257 (6) ◽  
pp. H1812-H1818 ◽  
Author(s):  
G. K. Savard ◽  
E. A. Richter ◽  
S. Strange ◽  
B. Kiens ◽  
N. J. Christensen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Muscle Mass ◽  
Nervous Activity ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Knee Extensors ◽  
Sympathetic Nervous Activity ◽  
Leg Blood Flow ◽  
Sympathetic Nervous

The purpose of this study was to determine the effect of increasing muscle mass involvement in dynamic exercise on both sympathetic nervous activation and local hemodynamic variables of individual active and inactive skeletal muscle groups. Six male subjects performed 15-min bouts of one-legged knee extension either alone or in combination with the knee extensors of the other leg and/or with the arms. The range of work intensities varied between 24 and 71% (mean) of subjects' maximal aerobic capacity (% VO2max). Leg blood flow, measured in the femoral vein by thermodilution, was determined in both legs. Arterial and venous plasma concentrations of norepinephrine (NE) and epinephrine were analyzed, and the calculated NE spillover was used as an index of sympathetic nervous activity to the limb. NE spillover increased gradually both in the resting, and to a larger extent in the exercising legs, with a steeper rise occurring approximately 70% VO2max. These increases were not associated with any significant changes in leg blood flow or leg vascular conductance at the exercise intensities examined. These results suggest that, as the total active muscle mass increases, the rise in sympathetic nervous activity to skeletal muscle, either resting or working at a constant load, is not associated with any significant neurogenic vasoconstriction and reduction in flow or conductance through the muscle vascular bed, during whole body exercise demanding up to 71% VO2max.

Is postexercise hypotension related to excess postexercise oxygen consumption through changes in leg blood flow?

2005 ◽  
Vol 98 (4) ◽  
pp. 1463-1468 ◽  
Author(s):  
Jay T. Williams ◽  
Mollie P. Pricher ◽  
John R. Halliwill
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Muscle Blood Flow ◽  
Causal Link ◽  
Skeletal Muscle Blood Flow ◽  
Leg Blood Flow ◽  
Postexercise Hypotension

After a single bout of aerobic exercise, oxygen consumption remains elevated above preexercise levels [excess postexercise oxygen consumption (EPOC)]. Similarly, skeletal muscle blood flow remains elevated for an extended period of time. This results in a postexercise hypotension. The purpose of this study was to explore the possibility of a causal link between EPOC, postexercise hypotension, and postexercise elevations in skeletal muscle blood flow by comparing the magnitude and duration of these postexercise phenomena. Sixteen healthy, normotensive, moderately active subjects (7 men and 9 woman, age 20–31 yr) were studied before and through 135 min after a 60-min bout of upright cycling at 60% of peak oxygen consumption. Resting and recovery V̇o2 were measured with a custom-built dilution hood and mass spectrometer-based metabolic system. Mean arterial pressure was measured via an automated blood pressure cuff, and femoral blood flow was measured using ultrasound. During the first hour postexercise, V̇o2 was increased by 11 ± 2%, leg blood flow was increased by 51 ± 18%, leg vascular conductance was increased by 56 ± 19%, and mean arterial pressure was decreased by 2.2 ± 1.0 mmHg (all P < 0.05 vs. preexercise). At the end of the protocol, V̇o2 remained elevated by 4 ± 2% ( P < 0.05), whereas leg blood flow, leg vascular conductance, and mean arterial pressure returned to preexercise levels (all P > 0.7 vs. preexercise). Taken together, these data demonstrate that EPOC and the elevations in skeletal muscle blood flow underlying postexercise hypotension do not share a common time course. This suggests that there is no causal link between these two postexercise phenomena.

scholarly journals Effects of gender on resting leg blood flow: implications for measurement of regional substrate oxidation

1998 ◽  
Vol 84 (1) ◽  
pp. 141-145 ◽  
Author(s):  
Michael D. Jensen ◽  
Tu T. Nguyen ◽  
A. Hernández Mijares ◽  
C. Michael Johnson ◽  
Michael J. Murray
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Respiratory Quotient ◽  
Substrate Oxidation ◽  
Fat Free Mass ◽  
Data Set ◽  
Men And Women ◽  
Leg Blood Flow ◽  
Meal Ingestion

Jensen, Michael D., Tu T. Nguyen, A. Hernández Mijares, C. Michael Johnson, and Michael J. Murray. Effects of gender on resting leg blood flow: implications for measurement of regional substrate oxidation. J. Appl. Physiol. 84(1): 141–145, 1998.—These studies were designed to examine whether the respiratory quotient (RQ) of leg tissue (primarily skeletal muscle) would increase to a greater degree in women than in men during meal ingestion. We found that mean leg and systemic RQ values were similar in men under both basal and fed conditions, whereas the agreement was poor in women. In women, leg RQ values tended to be greater than the systemic RQ, whereas splanchnic RQ values tended to be lower than the systemic RQ. The possibility that measurement imprecision accounted for the different findings in women could not be excluded because the arteriovenous blood O2 differences were almost twice as great in men as in women (53.7 ± 5.4 vs. 28.6 ± 2.9 ml of O2/l, respectively; P < 0.01), as were venoarterial blood CO2 differences. The smaller arteriovenous differences in women appeared to limit our ability to accurately measure their leg RQ values. O2 uptake relative to leg fat-free mass (FFM) was not different between men and women, whereas leg blood flow relative to leg FFM was greater in women than in men (55 ± 3 vs. 39 ± 2 ml ⋅ kg FFM−1 ⋅ min−1, respectively; P < 0.001). These findings were confirmed by examining data from other studies conducted in our laboratory to create a larger data set. We conclude that resting leg blood flow in women is greater (relative to FFM) than in men, making it more difficult to accurately measure leg RQ in women.

scholarly journals Therapeutic Angiogenesis by a “Dynamic Duo”: Simultaneous Expression of HGF and VEGF165 by Novel Bicistronic Plasmid Restores Blood Flow in Ischemic Skeletal Muscle

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1231
Author(s):  
Ekaterina Slobodkina ◽  
Maria Boldyreva ◽  
Maxim Karagyaur ◽  
Roman Eremichev ◽  
Natalia Alexandrushkina ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Growth Factor ◽  
Umbilical Vein ◽  
Limb Ischemia ◽  
Bidirectional Promoter ◽  
Capillary Density ◽  
Therapeutic Angiogenesis ◽  
Angiogenic Growth Factors ◽  
Umbilical Vein Endothelial Cells

Therapeutic angiogenesis is a promising strategy for relief of ischemic conditions, and gene delivery was used to stimulate blood vessels’ formation and growth. We have previously shown that intramuscular injection of a mixture containing plasmids encoding vascular endothelial growth factor (VEGF)165 and hepatocyte growth factor (HGF) leads to restoration of blood flow in mouse ischemic limb, and efficacy of combined delivery was superior to each plasmid administered alone. In this work, we evaluated different approaches for co-expression of HGF and VEGF165 genes in a panel of candidate plasmid DNAs (pDNAs) with internal ribosome entry sites (IRESs), a bidirectional promoter or two independent promoters for each gene of interest. Studies in HEK293T culture showed that all plasmids provided synthesis of HGF and VEGF165 proteins and stimulated capillary formation by human umbilical vein endothelial cells (HUVEC), indicating the biological potency of expressed factors. Tests in skeletal muscle explants showed a dramatic difference and most plasmids failed to express HGF and VEGF165 in a significant quantity. However, a bicistronic plasmid with two independent promoters (cytomegalovirus (CMV) for HGF and chicken b-actin (CAG) for VEGF165) provided expression of both grow factors in skeletal muscle at an equimolar ratio. Efficacy tests of bicistronic plasmid were performed in a mouse model of hind limb ischemia. Intramuscular administration of plasmid induced significant restoration of perfusion compared to an empty vector and saline. These findings were supported by increased CD31+ capillary density in animals that received pHGF/VEGF. Overall, our study reports a first-in-class candidate gene therapy drug to deliver two pivotal angiogenic growth factors (HGF and VEGF165) with properties that provide basis for future development of treatment for an unmet medical need—peripheral artery disease and associated limb ischemia.

scholarly journals α-Adrenergic receptor regulation of skeletal muscle blood flow during exercise in heart failure patients with reduced ejection fraction

2019 ◽  
Vol 316 (5) ◽  
pp. R512-R524 ◽  
Author(s):  
Zachary Barrett-O’Keefe ◽  
Joshua F. Lee ◽  
Stephen J. Ives ◽  
Joel D. Trinity ◽  
Melissa A. H. Witman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Ejection Fraction ◽  
Adrenergic Receptor ◽  
Muscle Blood Flow ◽  
Skeletal Muscle Blood Flow ◽  
Reduced Ejection Fraction ◽  
Leg Blood Flow ◽  
Related Increase

Patients suffering from heart failure with reduced ejection fraction (HFrEF) experience impaired limb blood flow during exercise, which may be due to a disease-related increase in α-adrenergic receptor vasoconstriction. Thus, in eight patients with HFrEF (63 ± 4 yr) and eight well-matched controls (63 ± 2 yr), we examined changes in leg blood flow (Doppler ultrasound) during intra-arterial infusion of phenylephrine (PE; an α1-adrenergic receptor agonist) and phentolamine (Phen; a nonspecific α-adrenergic receptor antagonist) at rest and during dynamic single-leg knee-extensor exercise (0, 5, and 10 W). At rest, the PE-induced reduction in blood flow was significantly attenuated in patients with HFrEF (−15 ± 7%) compared with controls (−36 ± 5%). During exercise, the controls exhibited a blunted reduction in blood flow induced by PE (−12 ± 4, −10 ± 4, and −9 ± 2% at 0, 5, and 10 W, respectively) compared with rest, while the PE-induced change in blood flow was unchanged compared with rest in the HFrEF group (−8 ± 5, −10 ± 3, and −14 ± 3%, respectively). Phen administration increased leg blood flow to a greater extent in the HFrEF group at rest (+178 ± 34% vs. +114 ± 28%, HFrEF vs. control) and during exercise (36 ± 6, 37 ± 7, and 39 ± 6% vs. 13 ± 3, 14 ± 1, and 8 ± 3% at 0, 5, and 10 W, respectively, in HFrEF vs. control). Together, these findings imply that a HFrEF-related increase in α-adrenergic vasoconstriction restrains exercising skeletal muscle blood flow, potentially contributing to diminished exercise capacity in this population.

Prostaglandin production contributes to exercise-induced vasodilation in heart failure

1997 ◽  
Vol 83 (6) ◽  
pp. 1933-1940 ◽  
Author(s):  
Chim C. Lang ◽  
Don B. Chomsky ◽  
Javed Butler ◽  
Shiv Kapoor ◽  
John R. Wilson
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Peak Exercise ◽  
Prostaglandin Production ◽  
Leg Blood Flow ◽  
Patients With Heart Failure ◽  
Prostaglandin F ◽  
Exercise Induced ◽  
Arteriolar Vasodilation

Lang, Chim C., Don B. Chomsky, Javed Butler, Shiv Kapoor, and John R. Wilson. Prostaglandin production contributes to exercise-induced vasodilation in heart failure. J. Appl. Physiol. 83(6): 1933–1940, 1997.—Endothelial release of prostaglandins may contribute to exercise-induced skeletal muscle arteriolar vasodilation in patients with heart failure. To test this hypothesis, we examined the effect of indomethacin on leg circulation and metabolism in eight chronic heart failure patients, aged 55 ± 4 yr. Central hemodynamics and leg blood flow, determined by thermodilution, and leg metabolic parameters were measured during maximum treadmill exercise before and 2 h after oral administration of indomethacin (75 mg). Leg release of 6-ketoprostaglandin F1α was also measured. During control exercise, leg blood flow increased from 0.34 ± 0.03 to 1.99 ± 0.19 l/min ( P < 0.001), leg O2 consumption from 13.6 ± 1.8 to 164.5 ± 16.2 ml/min ( P < 0.001), and leg prostanoid release from 54.1 ± 8.5 to 267.4 ± 35.8 pg/min ( P < 0.001). Indomethacin suppressed release of prostaglandin F1α( P < 0.001) throughout exercise and decreased leg blood flow during exercise ( P < 0.05). This was associated with a corresponding decrease in leg O2 consumption ( P < 0.05) and a higher level of femoral venous lactate at peak exercise ( P < 0.01). These data suggest that release of vasodilatory prostaglandins contributes to skeletal muscle arteriolar vasodilation in patients with heart failure.

Dynamic regulation of leg vasomotor tone in patients with chronic heart failure

1991 ◽  
Vol 71 (3) ◽  
pp. 1070-1075 ◽  
Author(s):  
M. J. Sullivan ◽  
F. R. Cobb
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Cardiac Output ◽  
Chronic Heart Failure ◽  
Left Ventricular ◽  
Work Rate ◽  
Vasomotor Tone ◽  
Leg Blood Flow ◽  
Leg Exercise

We examined the central hemodynamic (n = 5) and leg blood flow (n = 9) responses to one- and two-leg bicycle exercise in nine ambulatory patients with chronic heart failure due to left ventricular systolic dysfunction (ejection fraction 17 +/- 9%). During peak one- vs. two-leg exercise, leg blood flow (thermodilution) tended to be higher (1.99 +/- 0.91 vs. 1.67 +/- 0.91 l/min, P = 0.07), whereas femoral arteriovenous oxygen difference was lower (13.6 +/- 3.1 vs. 15.0 +/- 2.9 ml/dl, P less than 0.01). Comparison of data from exercise stages matched for single-leg work rate during one- vs. two-leg exercise demonstrated that cardiac output was similar while both oxygen consumption and central arteriovenous oxygen differences were lower, indicating relative improvement in the cardiac output response at a given single-leg work rate during one-leg exercise. This was accompanied by higher leg blood flow (1.56 +/- 0.76 vs. 1.83 +/- 0.72 l/min, P = 0.02) and a tendency for leg vascular resistance to be lower (92 +/- 54 vs. 80 +/- 48 Torr.l-1.min, P = 0.08) without any change in blood lactate. These data indicate that, in patients with chronic heart failure, leg vasomotor tone is dynamically regulated, independent of skeletal muscle metabolism, and is not determined solely by intrinsic abnormalities in skeletal muscle vasodilator capacity. Our results suggest that relative improvements in central cardiac function may lead to a reflex release of skeletal muscle vasoconstrictor tone in this disorder.

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