Reduced blood pressure responsiveness to skeletal muscle metaboreflex activation in older adults following inorganic nitrate supplementation

Aging is associated with increased peripheral chemoreceptor activity, reduced nitric oxide (NO) bioavailability, and attenuation of cardiovagal baroreflex sensitivity (BRS), collectively increasing the risk of cardiovascular disease. Evidence suggests that NO may attenuate peripheral chemoreflex sensitivity and increase BRS. Exogenous inorganic nitrate ([Formula: see text]) increases NO bioavailability via the [Formula: see text]-[Formula: see text]-NO pathway. Our hypothesis was that inorganic [Formula: see text] supplementation would attenuate peripheral chemoreflex sensitivity and enhance spontaneous cardiovagal BRS in older adults. We used a randomized, placebo-controlled crossover design in which 13 older (67 ± 3 yr old) adults ingested beetroot powder containing (BRA) or devoid of (BRP) [Formula: see text] and [Formula: see text] daily over 4 wk. Spontaneous cardiovagal BRS was assessed over 15 min of rest and was quantified using the sequence method. Chemoreflex sensitivity was assessed via ~5 min of hypoxia (10% fraction of inspired O2) and reported as the slope of the relationship between O2 saturation (%[Formula: see text]) and minute ventilation (in l/min) or heart rate (in beats/min). Ventilatory responsiveness to hypoxia was reduced after BRA (from −0.14 ± 0.04 to −0.05 ± 0.02 l·min−1·%[Formula: see text]−1, P = 0.01) versus BRP (from −0.10 ± 0.05 to −0.11 ± 0.05 l·min−1·%[Formula: see text]−1, P = 0.80), with no differences in heart rate responsiveness (BRA: from −0.47 ± 0.06 to −0.33 ± 0.04 beats·min−1·%[Formula: see text]−1, BRP: from −0.48 ± 0.07 to −0.42 ± 0.06 beats·min−1·%[Formula: see text]−1) between conditions (interaction effect, P = 0.41). Spontaneous cardiovagal BRS was unchanged after BRA and BRP (interaction effects, P = 0.69, 0.94, and 0.39 for all, up, and down sequences, respectively), despite a reduction in resting systolic and mean arterial blood pressure in the experimental (BRA) group ( P < 0.01 for both). These findings illustrate that inorganic [Formula: see text] supplementation attenuates peripheral chemoreflex sensitivity without concomitant change in spontaneous cardiovagal BRS in older adults. NEW & NOTEWORTHY Exogenous inorganic nitrate supplementation attenuates ventilatory, but not heart rate, responsiveness to abbreviated hypoxic exposure in older adults. Additionally, inorganic nitrate reduces systolic and mean arterial blood pressure without affecting spontaneous cardiovagal baroreflex sensitivity. These findings suggest that inorganic nitrate may attenuate sympathetically oriented pathologies associated with aging.

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Effects of handgrip exercise or inorganic nitrate supplementation on 24-h ambulatory blood pressure and peripheral arterial function in overweight and obese middle age and older adults: A pilot RCT

Maturitas ◽

10.1016/j.maturitas.2015.07.028 ◽

2015 ◽

Vol 82 (2) ◽

pp. 228-235 ◽

Cited By ~ 16

Author(s):

Jose Lara ◽

Ikponmwonsa Ogbonmwan ◽

Clio Oggioni ◽

Dingchang Zheng ◽

Othman Qadir ◽

...

Keyword(s):

Blood Pressure ◽

Older Adults ◽

Ambulatory Blood Pressure ◽

Middle Age ◽

Handgrip Exercise ◽

Arterial Function ◽

Inorganic Nitrate ◽

Pilot Rct ◽

Nitrate Supplementation ◽

Peripheral Arterial

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Inorganic nitrate supplementation attenuates conduit artery retrograde and oscillatory shear in older adults

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00843.2020 ◽

2021 ◽

Vol 320 (3) ◽

pp. H991-H998

Author(s):

Darren P. Casey ◽

Joshua M. Bock

Keyword(s):

Cardiovascular Disease ◽

Older Adults ◽

Brachial Artery ◽

Oscillatory Shear ◽

Atherosclerotic Cardiovascular Disease ◽

Conduit Artery ◽

Inorganic Nitrate ◽

Nitrate Supplementation ◽

First Time

We report for the first time, to our knowledge, that 4 wk of inorganic nitrate supplementation attenuates retrograde and oscillatory shear in the brachial artery of older adults. However, this was not associated with greater hyperemic or vasodilatory responses to exercise. In sum, these data highlight favorable changes in shear patterns with aging, which may reduce the risk of atherosclerotic cardiovascular disease.

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Inorganic nitrate supplementation and exercise. Is skeletal muscle involved in the heavy lifting?

The Journal of Physiology ◽

10.1113/jp278683 ◽

2019 ◽

Vol 597 (23) ◽

pp. 5521-5522

Author(s):

Joaquin Ortiz de Zevallos ◽

Jason D. Allen

Keyword(s):

Skeletal Muscle ◽

Inorganic Nitrate ◽

Nitrate Supplementation

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Effect of acute dietary nitrate supplementation on sympathetic vasoconstriction at rest and during exercise

Journal of Applied Physiology ◽

10.1152/japplphysiol.01053.2018 ◽

2019 ◽

Vol 127 (1) ◽

pp. 81-88 ◽

Cited By ~ 1

Author(s):

Christopher J. de Vries ◽

Darren S. DeLorey

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Skeletal Muscle ◽

Beetroot Juice ◽

Total Plasma ◽

Dietary Nitrate ◽

Arterial Blood ◽

Sympathetic Vasoconstriction ◽

Nitrate Supplementation ◽

Healthy Males

Dietary nitrate ([Formula: see text]) supplementation has been shown to reduce resting blood pressure. However, the mechanism responsible for the reduction in blood pressure has not been identified. Dietary [Formula: see text] supplementation may increase nitric oxide (NO) bioavailability, and NO has been shown to inhibit sympathetic vasoconstriction in resting and contracting skeletal muscle. Therefore, the purpose of this study was to investigate the hypothesis that acute dietary [Formula: see text] supplementation would attenuate sympathetic vasoconstrictor responsiveness at rest and during exercise. In a double-blind randomized crossover design, 12 men (23 ± 5 yr) performed a cold-pressor test (CPT) at rest and during moderate- and heavy-intensity alternate-leg knee-extension exercise after consumption of [Formula: see text] rich beetroot juice (~12.9 mmol [Formula: see text]) or a [Formula: see text]-depleted placebo (~0.13 mmol [Formula: see text]). Venous blood was sampled before and 2.5 h after the consumption of beetroot juice for the measurement of total plasma nitrite/[Formula: see text] [NOx]. Beat-by-beat blood pressure was measured by Finometer. Leg blood flow was measured at the femoral artery via Doppler ultrasound, and leg vascular conductance (LVC) was calculated. Sympathetic vasoconstrictor responsiveness was calculated as the percentage decrease in LVC in response to the CPT. Total plasma [NOx] was greater ( P < 0.001) in the [Formula: see text] (285 ± 120 µM) compared with the placebo (65 ± 30 µM) condition. However, mean arterial blood pressure and plasma catecholamines were not different ( P > 0.05) between [Formula: see text] and placebo conditions at rest or during moderate- and heavy-intensity exercise. Sympathetic vasoconstrictor responsiveness (Δ% LVC) was not different ( P > 0.05) between [Formula: see text] and placebo conditions at rest ([Formula: see text]: −33 ± 10%; placebo: −35 ± 11%) or during moderate ([Formula: see text]: −18 ± 8%; placebo: −20 ± 10%)- and heavy ([Formula: see text]: −12 ± 8%; placebo: −11 ± 9%)-intensity exercise. These data demonstrate that acute dietary [Formula: see text] supplementation does not alter sympathetic vasoconstrictor responsiveness at rest or during exercise in young healthy males. NEW & NOTEWORTHY Dietary nitrate may increase nitric oxide bioavailability, and nitric oxide has been shown to attenuate sympathetic vasoconstriction in resting and contracting skeletal muscle and enhance functional sympatholysis. However, the effect of dietary nitrate on sympathetic vasoconstrictor responsiveness is unknown. Acute dietary nitrate supplementation did not alter blood pressure or sympathetic vasoconstrictor responsiveness at rest or during exercise in young healthy males.

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Acute inorganic nitrate supplementation and the hypoxic ventilatory response in patients with obstructive sleep apnea

Journal of Applied Physiology ◽

10.1152/japplphysiol.00696.2020 ◽

2020 ◽

Author(s):

Joshua M. Bock ◽

Brady E. Hanson ◽

Thomas F. Asama ◽

Andrew J. Feider ◽

Satoshi Hanada ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Ventilatory Response ◽

High Dose ◽

Inorganic Nitrate ◽

Obstructive Sleep ◽

Chemoreflex Sensitivity ◽

Nitrate Supplementation ◽

High Doses ◽

Peripheral Chemoreflex

Patients with obstructive sleep apnea (OSA) have increased cardiovascular disease risk largely attributable to hypertension. Heightened peripheral chemoreflex sensitivity (i.e., exaggerated responsiveness to hypoxia) facilitates hypertension in these patients. Nitric oxide blunts the peripheral chemoreflex and patients with OSA have reduced nitric oxide bioavailability. We therefore investigated the dose-dependent effects of acute inorganic nitrate supplementation (beetroot juice), an exogenous nitric oxide source, on blood pressure and cardiopulmonary responses to hypoxia in patients with OSA using a randomized, double-blind, placebo-controlled crossover design. Fourteen patients with OSA (53±10years, 29.2±5.8kg/m2, apnea-hypopnea index=17.8±8.1, 43%F) completed three visits. Resting brachial blood pressure, as well as cardiopulmonary responses to inspiratory hypoxia, were measured before, and two hours after, acute inorganic nitrate supplementation (~0.10mmol [placebo], 4.03mmol [low-dose], and 8.06mmol [high-dose]). Placebo did not increase either plasma [nitrate] (30±52 to 52±23μM, P=0.26) or [nitrite] (266±153 to 277±164nM, P=0.21); however, both increased following low-(29±17 to 175±42μM, 220±137 to 514±352nM) and high-doses (26±11 to 292±90μM, 248±155 to 738±427nM, respectively, P<0.01 for all). Following placebo, systolic blood pressure increased (120±9 to128±10mmHg, P<0.05) whereas no changes were observed following low-(121±11 to 123±8mmHg, P=0.19) or high-dose (124±13 to 124±9mmHg, P=0.96). The peak ventilatory response to hypoxia increased following placebo (3.1±1.2 to 4.4±2.6L/min, P<0.01) but not low-(4.4±2.4 to 5.4±3.4L/min, P=0.11) or high-doses (4.3±2.3 to 4.8±2.7L/min, P=0.42). Inorganic nitrate did not change the heart rate responses to hypoxia (beverage-by-time P=0.64). Acute inorganic nitrate supplementation appears to blunt an early-morning rise in systolic blood pressure potentially through suppression of peripheral chemoreflex sensitivity in patients with OSA.

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Effects of Red Beetroot Juice and Inorganic Nitrate Supplementation on Oral Bacteria and Nitric Oxide Metabolites in Middle-Aged/Older Adults with Overweight and Obesity

Current Developments in Nutrition ◽

10.1093/cdn/nzaa045_061 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 428-428

Author(s):

Nicole Litwin ◽

Scott Wrigley ◽

Hannah Van Ark ◽

Shannon Hartley ◽

Kiri Michell ◽

...

Keyword(s):

Older Adults ◽

Oral Bacteria ◽

Overweight And Obesity ◽

Oral Microbiota ◽

Middle Aged ◽

Inorganic Nitrate ◽

Nitrate Supplementation ◽

Plasma Nitrite ◽

Reducing Bacteria ◽

Nitrate Reducing Bacteria

Abstract Objectives Dietary inorganic nitrate from foods such as red beetroot juice (RBJ) can contribute to nitric oxide (NO) bioavailability through the enterosalivary nitrate-nitrite-NO pathway. A critical step in this pathway is the reduction of nitrate to nitrite by oral bacteria. We investigated the effects of inorganic nitrate supplementation, as RBJ or placebo + potassium nitrate (PBO+NIT), on the oral microbiota, and its relationship with saliva and plasma NO metabolites and vascular endothelial function. Methods In a randomized, double-blind, placebo-controlled trial, we measured the abundance of oral nitrate-reducing bacteria in saliva samples from 15 middle-aged/older adults with overweight and obesity using 16 rRNA sequencing. We also assessed the relationship of oral nitrate-reducing bacteria with the physiological responses to acute (4 hours) and chronic (4 weeks) RBJ, PBO+NIT, nitrate-free RBJ, and placebo supplementation via measurement of saliva and plasma nitrate/nitrite (NOx), plasma nitrite levels, and reactive hyperemia index (RHI). Results A significant decrease in the alpha diversity metric, Pileou's Evenness, was detected after chronic consumption of PBO+NIT (0.69 ± 0.05 at week 0 vs. 0.65 ± 0.05 at week 4; P < 0.05), while there was a trend for a decline following RBJ consumption (0.69 ± 0.05 at week 0 vs. 0.65 ± 0.05 at week 4; P = 0.08). No significant differences in abundance of nitrate-reducing bacteria were observed after chronic supplementation, although abundance of the species Neisseria subflava was trending toward an increase in the RBJ group (10.8% at week 0 vs. 12.2% at week 4; P = 0.07). Plasma and saliva NOx increased from baseline and remained elevated for the 4-hour testing period after acute and chronic RBJ and PBO+NIT supplementation (all P < 0.05), while plasma nitrite only peaked at 2 hours in the RBJ group after acute supplementation and was significantly higher than PBO+NIT group (P < 0.01). RHI change from baseline to 4 hours was positively correlated with total abundance of nitrate-reducing species after chronic RBJ supplementation (r = 0.5; P = 0.05). Conclusions Acute and chronic RBJ and PBO+NIT supplementation increases NO metabolites and may alter the oral microbiota to favorably affect vascular endothelial function in middle-aged/older adults with overweight and obesity. Funding Sources NIFA, USDA.

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Sympathetic Activation due to Limb Venous Distension Is Preserved during Muscle Metaboreceptor Stimulation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00305.2020 ◽

2021 ◽

Author(s):

Jian Cui ◽

Cheryl Blaha ◽

Urs A. Leuenberger ◽

Lawrence I. Sinoway

Keyword(s):

Blood Pressure ◽

Skeletal Muscle ◽

Healthy Subjects ◽

Sympathetic Nerve Activity ◽

Muscle Sympathetic Nerve Activity ◽

Muscle Afferents ◽

Sympathetic Activation ◽

Nerve Activity ◽

Post Exercise ◽

Muscle Metaboreflex

Venous saline infusions in an arterially occluded forearm evokes reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in humans (venous distension reflex). It is unclear if the inputs from metabolically sensitive skeletal muscle afferents (i.e. muscle metaboreflex) would modify venous distension reflex. We hypothesized that muscle metaboreceptor stimulation might augment the venous distension reflex. BP (Finapres), heart rate (ECG), and MSNA (microneurography) were assessed in 18 young healthy subjects. In trial A, saline (5% forearm volume) was infused into the veins of an arterially occluded arm (non-handgrip trial). In trial B, subjects performed 2 min static handgrip followed by post exercise circulatory occlusion (PECO) of the arm. During PECO, saline was infused into veins of the arm (handgrip trial). In trial A, the infusion increased MSNA and BP as expected (both P < 0.001). In trial B, handgrip significantly raised MSNA, BP and venous lactic acid concentrations. Venous saline infusion during PECO further raised MSNA and BP (both P < 0.001). The changes in MSNA (D8.6 ± 1.5 to D10.6 ± 1.8 bursts/min, P = 0.258) and mean arterial pressure (P = 0.844) evoked by the infusion during PECO were not significantly different from those in the non-handgrip trial. These observations indicate that venous distension reflex responses are preserved during sympathetic activation mediated by the muscle metaboreflex.

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