Vascular Control of Nutrient Delivery by Flow Redistribution Within Muscle: Implications for Exercise and Post-Exercise Muscle Metabolism

Clark, Michael G.; Rattigan, Stephen; Dora, K A; Newman, John; Eldershaw, T. P. D.

doi:10.1055/s-2007-971935

Cited by 19 publications

(21 citation statements)

References 35 publications

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“…Although the effects of L-NMMA on glucose uptake were independent of changes in total LBF, the possibility remains that blood flow redistribution within the muscle contributed to our findings (58). If L-NMMA preferentially reduced flow through metabolically active (nutritive) areas while flow through metabolically inactive (nonnutritive) areas was increased, then glucose uptake might be reduced in the absence of any net change in flow (58).…”

Section: Discussionmentioning

confidence: 78%

“…If L-NMMA preferentially reduced flow through metabolically active (nutritive) areas while flow through metabolically inactive (nonnutritive) areas was increased, then glucose uptake might be reduced in the absence of any net change in flow (58). If operative, then this mechanism suggests greater NO-dependent dilation of nutritive vascular networks in individuals with diabetes compared with control subjects, which seems unlikely given the known impairment in NO-mediated endothelium-dependent dilation in these patients (59).…”

Section: Discussionmentioning

confidence: 99%

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Nitric Oxide Synthase Inhibition Reduces Glucose Uptake During Exercise in Individuals With Type 2 Diabetes More Than in Control Subjects

Kingwell¹,

Formosa²,

Muhlmann³

et al. 2002

Diabetes

131

134

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Nitric oxide (NO) synthase inhibition reduces leg glucose uptake during cycling without reducing leg blood flow (LBF) in young, healthy individuals. This study sought to determine the role of NO in glucose uptake during exercise in individuals with type 2 diabetes. Nine men with type 2 diabetes and nine control subjects matched for age, sex, peak pulmonary oxygen uptake (VO 2 peak), and weight completed two 25-min bouts of cycling exercise at 60 ؎ 2% VO 2 peak, separated by 90 min. N G -monomethyl-L-arginine (L-NMMA) (total dose 6 mg/kg) or placebo was administered into the femoral artery for the final 15 min of exercise in a counterbalanced, blinded, crossover design. LBF was measured by thermodilution in the femoral vein, and leg glucose uptake was calculated as the product of LBF and femoral arteriovenous glucose difference. During exercise with placebo, glucose uptake was not different between control subjects and individuals with diabetes; however, LBF was lower and arterial plasma glucose and insulin levels were higher in individuals with diabetes. L-NMMA had no effect on LBF or arterial plasma glucose and insulin concentrations during exercise in both groups. L-NMMA significantly reduced leg glucose uptake in both groups, with a significantly greater reduction (P ‫؍‬ 0.04) in the diabetic group (75 ؎ 13%, 5 min after L-NMMA) compared with the control group (34 ؎ 14%, 5 min after L-NMMA). These data suggest a greater reliance on NO for glucose uptake during exercise in individuals with type 2 diabetes compared with control subjects.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Nitric Oxide Synthase Inhibition Reduces Glucose Uptake During Exercise in Individuals With Type 2 Diabetes More Than in Control Subjects

Kingwell¹,

Formosa²,

Muhlmann³

et al. 2002

Diabetes

131

134

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“…It should be recognized that the intermittent character of capillary flow and capillary flow distribution is determined not only by the precapillary arteriolar network, but also by the characteristics of the capillary network itself (28,29). This may explain why experimental studies have demonstrated that insulin-mediated glucose uptake in skeletal muscle can be influenced by changes in capillary perfusion, even if total flow to the muscle remains constant (5-7).…”

Section: Discussionmentioning

confidence: 99%

Direct Evidence for Insulin-Induced Capillary Recruitment in Skin of Healthy Subjects During Physiological Hyperinsulinemia

Serné

IJzerman

Gans³

et al. 2002

Diabetes

157

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It has been proposed that insulin-mediated changes in muscle perfusion modulate insulin-mediated glucose uptake. However, the putative effects of insulin on the microcirculation that permit such modulation have not been studied in humans. We examined the effects of systemic hyperinsulinemia on skin microvascular function in eight healthy nondiabetic subjects. In addition, the effects of locally administered insulin on skin blood flow were assessed in 10 healthy subjects. During a hyperinsulinemic clamp, we measured leg blood flow with venous occlusion plethysmography, skin capillary density with capillaroscopy, endothelium-(in)dependent vasodilatation of skin microcirculation with iontophoresis of acetylcholine and sodium nitroprusside combined with laser Doppler fluxmetry, and skin vasomotion by Fourier analysis of microcirculatory blood flow. To exclude nonspecific changes in the hemodynamic variables, a time-volume control study was performed. Insulin iontophoresis was used to study the local effects of insulin on skin blood flow. Compared to the control study, systemic hyperinsulinemia caused an increase in leg blood flow (؊0.54 ؎ 0.93 vs. 1.97 ؎ 1.1 ml ⅐ min ؊1 ⅐ dl ؊1 ; P < 0.01), an increase in the number of perfused capillaries in the resting state (؊3.7 ؎ 3.0 vs. 3.4 ؎ 1.4 per mm 2 ; P < 0.001) and during postocclusive reactive hyperemia (؊0.8 ؎ 2.2 vs. 5.1 ؎ 3.7 per mm 2 ; P < 0.001), an augmentation of the vasodilatation caused by acetylcholine (722 ؎ 206 vs. 989 ؎ 495%; P < 0.05) and sodium nitroprusside (618 ؎ 159 vs. 788 ؎ 276%; P < 0.05), and a change in vasomotion by increasing the relative contribution of the 0.01-to 0.02-Hz and 0.4-to 1.6-Hz spectral components (P < 0.05). Compared to the control substance, locally administered insulin caused a rapid increase (ϳ13.5 min) in skin microcirculatory blood flow (34.4 ؎ 42.5 vs. 82.8 ؎ 85.7%; P < 0.05). In conclusion, systemic hyperinsulinemia in skin 1) induces recruitment of capillaries, 2) augments nitric oxide؊mediated vasodilatation, and 3) influences vasomotion. In addition, locally administered insulin 4) induces a rapid increase in total skin blood flow, independent of systemic effects. Diabetes 51: 1515-1522, 2002

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“…These include: 1. Muscle V̇ O 2 at rest and during submaximal contractions is O 2 delivery limited (Clark et al 1998, 2001). In healthy muscle at rest and during contractions V̇ O 2 is known to be controlled by intramyocyte high-energy phosphate signaling (Meyer and Foley, 1996) and, other than close to maximal V̇ O 2 (Richardson et al 1993; Wagner et al 1997; Poole, 1997), is not limited by O 2 supply.…”

Section: Presumptions Arising From “Capillary Recruitment”mentioning

confidence: 99%

Dynamics of muscle microcirculatory and blood–myocyte O₂ flux during contractions

et al. 2011

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The O2 requirements of contracting skeletal muscle may increase 100-fold above rest. In 1919 August Krogh’s brilliant insights recognized the capillary as the principal site for this increased blood-myocyte O2 flux. Based on the premise that most capillaries did not sustain RBC flux at rest Krogh proposed that capillary recruitment (i.e., initiation of red blood cell (RBC) flux in previously non-flowing capillaries) increased the capillary surface area available for O2 flux and reduced mean capillary-to-mitochondrial diffusion distances. More modern experimental approaches reveal that most muscle capillaries may support RBC flux at rest. Thus, rather than contraction-induced capillary recruitment per se, increased RBC flux and hematocrit within already-flowing capillaries likely elevate perfusive and diffusive O2 conductances and hence blood-myocyte O2 flux. Additional surface area for O2 exchange is recruited but, crucially, this may occur along the length of already-flowing capillaries (i.e. longitudinal recruitment). Today, the capillary is still considered the principal site for O2 and substrate delivery to contracting skeletal muscle. Indeed, the presence of very low intramyocyte O2 partial pressures (PO2’s) and the absence of PO2 gradients, whilst refuting the relevance of diffusion distances, place an even greater importance on capillary hemodynamics. This emergent picture calls for a paradigm-shift in our understanding of the function of capillaries by de-emphasizing de novo ‘capillary recruitment.’ Diseases such as heart failure impair blood-myocyte O2 flux, in part, by decreasing the proportion of RBC-flowing capillaries. Knowledge of capillary function in healthy muscle is requisite for identification of pathology and efficient design of therapeutic treatments.

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Vascular Control of Nutrient Delivery by Flow Redistribution Within Muscle: Implications for Exercise and Post-Exercise Muscle Metabolism

Cited by 19 publications

References 35 publications

Nitric Oxide Synthase Inhibition Reduces Glucose Uptake During Exercise in Individuals With Type 2 Diabetes More Than in Control Subjects

Nitric Oxide Synthase Inhibition Reduces Glucose Uptake During Exercise in Individuals With Type 2 Diabetes More Than in Control Subjects

Direct Evidence for Insulin-Induced Capillary Recruitment in Skin of Healthy Subjects During Physiological Hyperinsulinemia

Dynamics of muscle microcirculatory and blood–myocyte O₂ flux during contractions

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Vascular Control of Nutrient Delivery by Flow Redistribution Within Muscle: Implications for Exercise and Post-Exercise Muscle Metabolism

Cited by 19 publications

References 35 publications

Nitric Oxide Synthase Inhibition Reduces Glucose Uptake During Exercise in Individuals With Type 2 Diabetes More Than in Control Subjects

Nitric Oxide Synthase Inhibition Reduces Glucose Uptake During Exercise in Individuals With Type 2 Diabetes More Than in Control Subjects

Direct Evidence for Insulin-Induced Capillary Recruitment in Skin of Healthy Subjects During Physiological Hyperinsulinemia

Dynamics of muscle microcirculatory and blood–myocyte O2 flux during contractions

Contact Info

Product

Resources

About

Dynamics of muscle microcirculatory and blood–myocyte O₂ flux during contractions