Effects of nitrate supplementation via beetroot juice on contracting rat skeletal muscle microvascular oxygen pressure dynamics

Ferguson, Scott K.; Hirai, Daniel M.; Copp, Steven W.; Holdsworth, Clark; Allen, Jason D.; Jones, Andrew M.; Musch, Timothy I.; Poole, David C.

doi:10.1016/j.resp.2013.04.001

Cited by 59 publications

(62 citation statements)

References 42 publications

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“…However, muscle [O 2 Hb] was increased at baseline and throughout exercise, phase II V O 2 kinetics was 23% faster, and exercise tolerance was extended by 22% in 115-BR compared with 115-PLA. Therefore, taken together with our previous findings (12) and consistent with recent results using murine models (24,25,34), the results of the current study demonstrate a preferential effect of NO 3 Ϫ on physiological responses in type II muscle in humans.…”

Section: Resultssupporting

confidence: 93%

“…There is also evidence to suggest that pulmonary V O 2 kinetics is slower (11, 18) and the V O 2 slow component is increased (11, 52) when cycling at very high compared with very low pedal cadences. Dietary NO 3 Ϫ supplementation has been shown to increase muscle blood flow (24), lower the O 2 (3,4,42,43,58,61) and ATP (3) requirements of muscle contraction, and improve the matching between muscle O 2 supply and muscle O 2 utilization (4,25,26). Therefore, this potential for enhanced contractile efficiency and perfusion distribution with NO 3 Ϫ supplementation might improve muscle oxygenation, V O 2 kinetics, and exercise toler-…”

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confidence: 99%

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Inorganic nitrate supplementation improves muscle oxygenation, O₂uptake kinetics, and exercise tolerance at high but not low pedal rates

Bailey

Varnham

DiMenna

et al. 2015

Journal of Applied Physiology

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103

114

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Bailey SJ, Varnham RL, DiMenna FJ, Breese BC, Wylie LJ, Jones AM. Inorganic nitrate supplementation improves muscle oxygenation, O2 uptake kinetics, and exercise tolerance at high but not low pedal rates. J Appl Physiol 118: 1396 -1405, 2015. First published April 9, 2015 doi:10.1152/japplphysiol.01141.2014.-We tested the hypothesis that inorganic nitrate (NO3 Ϫ ) supplementation would improve muscle oxygenation, pulmonary oxygen uptake (V O2) kinetics, and exercise tolerance (Tlim) to a greater extent when cycling at high compared with low pedal rates. In a randomized, placebo-controlled cross-over study, seven subjects (mean Ϯ SD, age 21 Ϯ 2 yr, body mass 86 Ϯ 10 kg) completed severe-intensity step cycle tests at pedal cadences of 35 rpm and 115 rpm during separate nine-day supplementation periods with NO3 Ϫ -rich beetroot juice (BR) (providing 8.4 mmol NO3 Ϫ /day) and placebo (PLA). Compared with PLA, plasma nitrite concentration increased 178% with BR (P Ͻ 0.01). There were no significant differences in muscle oxyhemoglobin concentration ([O2Hb]), phase II V O2 kinetics, or Tlim between BR and PLA when cycling at 35 rpm (P Ͼ 0.05). However, when cycling at 115 rpm, muscle [O2Hb] was higher at baseline and throughout exercise, phase II V O2 kinetics was faster (47 Ϯ 16 s vs. 61 Ϯ 25 s; P Ͻ 0.05), and Tlim was greater (362 Ϯ 137 s vs. 297 Ϯ 79 s; P Ͻ 0.05) with BR compared with PLA. These results suggest that short-term BR supplementation can increase muscle oxygenation, expedite the adjustment of oxidative metabolism, and enhance exercise tolerance when cycling at a high, but not a low, pedal cadence in healthy recreationally active subjects. These findings support recent observations that NO3 Ϫ supplementation may be particularly effective at improving physiological and functional responses in type II muscle fibers. nitric oxide; vascular function; oxidative metabolism; exercise performance; fatigue NITRIC OXIDE (NO) IS A DIFFUSIBLE GAS that impacts a plethora of physiological responses including skeletal muscle perfusion, metabolism, force production, and fatigue resistance (56). It is well documented that NO is produced by the nitric oxide synthase enzymes, which catalyze the complex five-electron oxidation of the semiessential amino acid, L-arginine (10). More recently, there has been a growing appreciation of the potential for NO synthesis from the simple one-electron reduction of nitrite (NO 2 Ϫ ), in a reaction catalyzed by numerous NO 2 Ϫ reductases (44, 57). Importantly, increasing the intake of dietary inorganic nitrate (NO 3 Ϫ ), which passes into the enterosalivary circulation for subsequent reduction to NO 2 Ϫ by oral anaerobes (19), has been shown to positively impact NO biomarkers, exercise efficiency, and exercise tolerance in recreationally active subjects (3,4,12,42,43,58,61). Therefore, supplementation with NO 3 Ϫ appears to represent an effective dietary intervention to improve NO bioavailability, contractile efficiency, and fatigue resistance.Results from in vitro studies suggest that th...

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Section: Resultssupporting

confidence: 93%

mentioning

confidence: 99%

Inorganic nitrate supplementation improves muscle oxygenation, O₂uptake kinetics, and exercise tolerance at high but not low pedal rates

Bailey

Varnham

DiMenna

et al. 2015

Journal of Applied Physiology

Self Cite

103

114

View full text Add to dashboard Cite

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“…Thus we were unable to quantify either the contraction intensity or the “relative” exercise intensity associated with each work level of our graded forearm exercise protocol. This is an important consideration given the intensity-dependent role of nitric oxide for muscle blood flow responses to exercise (Ferguson et al 2013a; Wray et al 2011) and the ergogenic/metabolic effects of dietary nitrate supplementation (Bailey et al 2009; Bescos et al 2012; Jones et al 2011; Lansley et al 2011; Vanhatalo et al 2011). To address this issue, we closely compared brachial artery blood flow, shear rate, and dilator responses between our subjects and the handgrip exercise study of Wray et al (2011), which examined the nitric oxide dependency of these responses in healthy young adults using a protocol with a similar number of exercise stages (n=6) and work/rest durations (3 min/1 min).…”

Section: Discussionmentioning

confidence: 99%

Acute dietary nitrate supplementation does not augment submaximal forearm exercise hyperemia in healthy young men

Kim

Moore

Maurer

et al. 2015

Appl. Physiol. Nutr. Metab.

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Despite the popularity of dietary nitrate supplementation and the growing evidence base of its potential ergogenic and vascular health benefits, there is no direct information about its effects on exercising limb blood flow in humans. We hypothesized that acute dietary nitrate supplementation from beetroot juice would augment the increases in forearm blood flow, as well as the progressive dilation of the brachial artery, during graded handgrip exercise in healthy young men. In a randomized, double-blind, placebo-controlled crossover study, 12 young (22 ± 2 years) healthy men consumed a beetroot juice (140 mL Beet-It Sport, James White Juice Company) that provided 12.9 mmol (0.8 g) of nitrate or placebo (nitrate-depleted Beet-It Sport) on 2 study visits. At 3 h postconsumption, brachial artery diameter, flow, and blood velocity were measured (Doppler ultrasound) at rest and during 6 exercise intensities. Nitrate supplementation raised plasma nitrate (19.5-fold) and nitrite (1.6-fold) concentrations, and lowered resting arterial pulse wave velocity (PWV) versus placebo (all p < 0.05) indicating absorption, conversion, and a biological effect of this supplement. The supplement-associated lowering of PWV was also negatively correlated with plasma nitrite (r = -0.72, p = 0.0127). Despite these systemic effects, nitrate supplementation had no effect on brachial artery diameter, flow, or shear rates at rest (all p ≥ 0.28) or during any exercise workload (all p ≥ 0.18). These findings suggest that acute dietary nitrate supplementation favorably modifies arterial PWV, but does not augment blood flow or brachial artery vasodilation during non-fatiguing forearm exercise in healthy young men.

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“…Mechanistic investigations have revealed that NO 3 Ϫ supplementation increases exercising skeletal muscle blood flow (BF) (18), skeletal muscle microvascular PO 2 (17,19), and the rate of skeletal muscle force development (24), particularly in muscles composed of predominantly fast twitch fibers. This fiber type preferential effect is likely due to the lower PO 2 /pH environment in contracting fast twitch muscle (IIb ϩ IId/x fibers) (40), an environment exacerbated by CHF.…”

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Effects of nitrite infusion on skeletal muscle vascular control during exercise in rats with chronic heart failure

Glean

Ferguson

Holdsworth

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Ϫ to NO may impact exercise-induced hyperemia, particularly in muscles with pathologically reduced O 2 delivery. We tested the hypothesis that NO 2 Ϫ infusion would increase exercising skeletal muscle blood flow (BF) and vascular conductance (VC) in CHF rats with a preferential effect in muscles composed primarily of type IIb ϩ IId/x fibers. CHF (coronary artery ligation) was induced in adult male Sprague-Dawley rats. After a Ͼ21-day recovery, mean arterial pressure (MAP; carotid artery catheter) and skeletal muscle BF (radiolabeled microspheres) were measured during treadmill exercise (20 m/min, 5% incline) with and without NO 2 Ϫ infusion. The myocardial infarct size (35 Ϯ 3%) indicated moderate CHF. NO 2 Ϫ infusion increased total hindlimb skeletal muscle VC (CHF: 0.85 Ϯ 0.09 ml·min Ϫ1 ·100 g Ϫ1 ·mmHg Ϫ1 and CHF ϩ NO 2 Ϫ : 0.93 Ϯ 0.09 ml·min Ϫ1 ·100 g Ϫ1 ·mmHg Ϫ1 , P Ͻ 0.05) without changing MAP (CHF: 123 Ϯ 4 mmHg and CHF ϩ NO 2 Ϫ : 120 Ϯ 4 mmHg, P ϭ 0.17). Total hindlimb skeletal muscle BF was not significantly different (CHF: 102 Ϯ 7 and CHF ϩ NO 2 Ϫ : 109 Ϯ 7 ml·min Ϫ1 ·100 g Ϫ1 ml·min Ϫ1 ·100 g Ϫ1 , P Ͼ 0.05). BF increased in 6 (ϳ21%) and VC in 8 (ϳ29%) of the 28 individual muscles and muscle parts. Muscles and muscle portions exhibiting greater BF and VC after NO 2 Ϫ infusion comprised Ն63% type IIb ϩ IId/x muscle fibers. These data demonstrate that NO 2 Ϫ infusion can augment skeletal muscle vascular control during exercise in CHF rats. Given the targeted effects shown herein, a NO 2 Ϫ -based therapy may provide an attractive "needs-based" approach for treatment of the vascular dysfunction in CHF. CHRONIC HEART FAILURE (CHF) is characterized by a combination of central and peripheral circulatory dysfunction that ultimately impairs exercise tolerance and quality of life (30,47). About 23 million individuals worldwide suffer from this disease (37), and while central cardiac dysfunction is fundamental to the etiology of CHF, the peripheral vascular impairments induced by CHF are of paramount importance. CHFinduced vascular dysregulation is thought to be due, in part, to reduced nitric oxide (NO)-mediated function (Ref. 20; for a review, see Ref. 47). Although exercise rehabilitation represents an effective therapeutic modality for treating CHF (9), reduced NO bioavailability in CHF is associated with an impaired ability to perform exercise and/or even complete daily physical activities. Consequently, interventions that increase NO bioavailability may ameliorate the skeletal muscle vascular dysfunction evident in this disease (20,25) and thus have great potential to improve exercise tolerance and quality of life in this population.NO is synthesized endogenously via three isoforms of NO synthase (NOS) as well as by the nonenzymatic reduction of NO 3 Ϫ to NO 2 Ϫ and, finally, to NO (for a review, see Ref. 38). The contribution of the NO 3 Ϫ -NO 2 Ϫ -NO pathway can be upregulated when plasma NO 2 Ϫ concentration is increased either by dietary means (e.g., via beetroot juice) or direct venous or arterial NO 2 Ϫ...

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Effects of nitrate supplementation via beetroot juice on contracting rat skeletal muscle microvascular oxygen pressure dynamics

Cited by 59 publications

References 42 publications

Inorganic nitrate supplementation improves muscle oxygenation, O₂uptake kinetics, and exercise tolerance at high but not low pedal rates

Inorganic nitrate supplementation improves muscle oxygenation, O₂uptake kinetics, and exercise tolerance at high but not low pedal rates

Acute dietary nitrate supplementation does not augment submaximal forearm exercise hyperemia in healthy young men

Effects of nitrite infusion on skeletal muscle vascular control during exercise in rats with chronic heart failure

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Effects of nitrate supplementation via beetroot juice on contracting rat skeletal muscle microvascular oxygen pressure dynamics

Cited by 59 publications

References 42 publications

Inorganic nitrate supplementation improves muscle oxygenation, O2uptake kinetics, and exercise tolerance at high but not low pedal rates

Inorganic nitrate supplementation improves muscle oxygenation, O2uptake kinetics, and exercise tolerance at high but not low pedal rates

Acute dietary nitrate supplementation does not augment submaximal forearm exercise hyperemia in healthy young men

Effects of nitrite infusion on skeletal muscle vascular control during exercise in rats with chronic heart failure

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Product

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Inorganic nitrate supplementation improves muscle oxygenation, O₂uptake kinetics, and exercise tolerance at high but not low pedal rates

Inorganic nitrate supplementation improves muscle oxygenation, O₂uptake kinetics, and exercise tolerance at high but not low pedal rates