Effect of sodium nitrite on local control of contracting skeletal muscle microvascular oxygen pressure in healthy rats

Colburn, Trenton D.; Ferguson, Scott K.; Holdsworth, Clark; Craig, Jesse C.; Musch, Timothy I.; Poole, David C.

doi:10.1152/japplphysiol.00367.2016

Cited by 13 publications

(7 citation statements)

References 61 publications

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“…Previous studies have demonstrated augmented blood flow and elevated PO 2 mv utilizing exogenous nitric oxide donors such as sodium nitroprusside and nitrate/nitrite supplementation in health and disease (Colburn et al . 2017, Craig et al . 2018, 2019 b , Ferguson et al .…”

Section: Discussionmentioning

confidence: 99%

Transcapillary PO₂ gradients in contracting muscles across the fibre type and oxidative continuum

Colburn

Hirai

Craig

et al. 2020

The Journal of Physiology

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Within skeletal muscle the greatest resistance to oxygen transport is thought to reside across the short distance at the red blood cell-myocyte interface. These structures generate a significant transmural oxygen pressure (PO 2) gradient in mixed fibre-type muscle. r Increasing O 2 flux across the capillary wall during exercise depends on: (i) the transmural O 2 pressure gradient, which is maintained in mixed-fibre muscle, and/or (ii) elevating diffusing properties between microvascular and interstitial compartments resulting, in part, from microvascular haemodynamics and red blood cell distribution. r We evaluated the PO 2 within the microvascular and interstitial spaces of muscles spanning the slow-to fast-twitch fibre and high-to low-oxidative capacity spectrums, at rest and during contractions, to assess the magnitude of transcapillary PO 2 gradients in rats. r Our findings demonstrate that, across the metabolic rest-contraction transition, the transcapillary pressure gradient for O 2 flux is: (i) maintained in all muscle types, and (ii) the lowest in contracting highly oxidative fast-twitch muscle.

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Section: Discussionmentioning

confidence: 99%

Transcapillary PO₂ gradients in contracting muscles across the fibre type and oxidative continuum

Colburn

Hirai

Craig

et al. 2020

The Journal of Physiology

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“…This reduced NO bioavailability to the upstream resistance vasculature is believed to be the primary cause of stopped capillaries and compromised muscle P O 2mv and D O 2 m in HF (Ferreira et al 2006;Hirai et al 2015), but whether increasing NO bioavailability exogenously re-establishes RBC flux in stopped capillaries in HF remains to be conclusively resolved. Notwithstanding the above, targeting the NO pathway via either direct sodium nitroprusside or nitrite superfusion (Ferreira et al 2006;Colburn et al 2017), nitrite infusion (Glean et al 2015;Ferguson et al 2016a) or dietary nitrate supplementation does increaseQ and P O 2mv in contracting healthy and HF rat muscles (Ferguson et al 2013a(Ferguson et al ,b, 2015(Ferguson et al , 2016bJones et al 2016;reviewed by Hirai et al 2015;Poole, 2019). NO raises P O 2mv by not only elevatingQ O 2 , as discussed above, but also decreasingV O 2 (Larsen et al 2007).…”

Section: Alternative Nitric Oxide Pathway Therapeutic Interventions Tmentioning

confidence: 99%

The role of vascular function on exercise capacity in health and disease

Poole

Behnke

Musch

2020

The Journal of Physiology

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Three sentinel parameters of aerobic performance are the maximal oxygen uptake (V̇O2normalmax), critical power (CP) and speed of the V̇normalO2 kinetics following exercise onset. Of these, the latter is, perhaps, the cardinal test of integrated function along the O2 transport pathway from lungs to skeletal muscle mitochondria. Fast V̇normalO2 kinetics demands that the cardiovascular system distributes exercise‐induced blood flow elevations among and within those vascular beds subserving the contracting muscle(s). Ideally, this process must occur at least as rapidly as mitochondrial metabolism elevates V̇normalO2. Chronic disease and ageing create an O2 delivery (i.e. blood flow × arterial [O2], Q̇normalO2) dependency that slows V̇normalO2 kinetics, decreasing CP and V̇O2normalmax, increasing the O2 deficit and sowing the seeds of exercise intolerance. Exercise training, in contrast, does the opposite. Within the context of these three parameters (see Graphical Abstract), this brief review examines the training‐induced plasticity of key elements in the O2 transport pathway. It asks how structural and functional vascular adaptations accelerate and redistribute muscle Q̇normalO2 and thus defend microvascular O2 partial pressures and capillary blood–myocyte O2 diffusion across a ∼100‐fold range of muscle V̇normalO2 values. Recent discoveries, especially in the muscle microcirculation and Q̇normalO2‐to‐V̇normalO2 heterogeneity, are integrated with the O2 transport pathway to appreciate how local and systemic vascular control helps defend V̇normalO2 kinetics and determine CP and V̇O2normalmax in health and how vascular dysfunction in disease predicates exercise intolerance. Finally, the latest evidence that nitrate supplementation improves vascular and therefore aerobic function in health and disease is presented.

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“…40-45 Inorganic nitrate and nitrite improve skeletal muscle microvascular conductance during exercise 46 and increase capillary O 2 tension facilitating O 2 diffusion into muscle cells. 47 Nitrite increases mitochondrial efficiency in skeletal muscle 48 and improves insulin sensitivity and glucose uptake. 49 A recent study in human HFrEF demonstrated improvements in muscle power with acute inorganic nitrate administration.…”

Section: Pathophysiology Of Hfpefmentioning

confidence: 99%

INDIE-HFpEF (Inorganic Nitrite Delivery to Improve Exercise Capacity in Heart Failure With Preserved Ejection Fraction)

Reddy

Lewis

Shah

et al. 2017

Circ: Heart Failure

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Approximately half of patients with heart failure (HF) have preserved ejection fraction (HFpEF). There is no proven treatment that improves outcome. The pathophysiology of HFpEF is complex and includes left ventricular (LV) systolic and diastolic dysfunction, pulmonary vascular disease, endothelial dysfunction, and peripheral abnormalities. Multiple lines of evidence point to impaired nitric oxide-cyclic guanosine monophosphate (NO-cGMP) bioavailability as playing a central role in each of these abnormalities. In contrast to traditional organic nitrate therapies, an alternative strategy to restore NO-cGMP signaling is via inorganic nitrite. Inorganic nitrite, previously considered to be an inert byproduct of NO metabolism, functions as an important in vivo reservoir for NO generation, particularly under hypoxic and acidemic conditions. As such, inorganic nitrite becomes most active at times of greater need for NO signaling, as during exercise when LV filling pressures and pulmonary artery pressures increase. Herein, we present the rationale and design for the Inorganic Nitrite Delivery to Improve Exercise Capacity in Heart Failure with Preserved Ejection Fraction (INDIE-HFpEF) trial, which is a multicenter, randomized, double-blind, placebo controlled crossover study assessing the effect of inhaled inorganic nitrite on peak exercise capacity, conducted in the NHLBI-sponsored Heart Failure Clinical Research Network. Clinical Trial Registration: clinicaltrials.gov; NCT02742129

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Effect of sodium nitrite on local control of contracting skeletal muscle microvascular oxygen pressure in healthy rats

Cited by 13 publications

References 61 publications

Transcapillary PO₂ gradients in contracting muscles across the fibre type and oxidative continuum

Transcapillary PO₂ gradients in contracting muscles across the fibre type and oxidative continuum

The role of vascular function on exercise capacity in health and disease

INDIE-HFpEF (Inorganic Nitrite Delivery to Improve Exercise Capacity in Heart Failure With Preserved Ejection Fraction)

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Effect of sodium nitrite on local control of contracting skeletal muscle microvascular oxygen pressure in healthy rats

Cited by 13 publications

References 61 publications

Transcapillary PO2 gradients in contracting muscles across the fibre type and oxidative continuum

Transcapillary PO2 gradients in contracting muscles across the fibre type and oxidative continuum

The role of vascular function on exercise capacity in health and disease

INDIE-HFpEF (Inorganic Nitrite Delivery to Improve Exercise Capacity in Heart Failure With Preserved Ejection Fraction)

Contact Info

Product

Resources

About

Transcapillary PO₂ gradients in contracting muscles across the fibre type and oxidative continuum

Transcapillary PO₂ gradients in contracting muscles across the fibre type and oxidative continuum