Inorganic nitrate supplementation attenuates peripheral chemoreflex sensitivity but does not improve cardiovagal baroreflex sensitivity in older adults

Abstract

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 (BR) or devoid of (BR) [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 O) and reported as the slope of the relationship between O saturation (%[Formula: see text]) and minute ventilation (in l/min) or heart rate (in beats/min). Ventilatory responsiveness to hypoxia was reduced after BR (from -0.14 ± 0.04 to -0.05 ± 0.02 l·min·%[Formula: see text], P = 0.01) versus BR (from -0.10 ± 0.05 to -0.11 ± 0.05 l·min·%[Formula: see text], P = 0.80), with no differences in heart rate responsiveness (BR: from -0.47 ± 0.06 to -0.33 ± 0.04 beats·min·%[Formula: see text], BR: from -0.48 ± 0.07 to -0.42 ± 0.06 beats·min·%[Formula: see text]) between conditions (interaction effect, P = 0.41). Spontaneous cardiovagal BRS was unchanged after BR and BR (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 (BR) 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.

Mechanisms underlying blood pressure reduction by dietary inorganic nitrate

“…Either the blood pressure effect is not significant enough to induce such a response or there might be an inhibitory effect of nitrate on baroreflex. However, a couple of human studies do not support an effect of dietary nitrate on baroreceptor sensitivity . A direct negative inotropic effect of nitrate on the myocardium would contribute to a lower blood pressure.…”

Carotid chemoreceptors: the link between pulmonary and cardiovascular disease?

“…For example, chronic supplementation of inorganic nitrate in the form of beetroot juice increases circulating NO bioavailability via the nitrate‐nitrite‐nitric oxide pathway, and has been show to attenuate carotid chemoreflex sensitivity (Bock et al . ). While this study (Bock et al .…”

“…While this study (Bock et al . ) was not designed to investigate vascular function (e.g. arterial stiffness, vasodilatation), it did provide compelling evidence to support the concept that carotid chemoreflex activity can be reduced in a healthy, older population by boosting NO bioavailability using a nutraceutical intervention.…”

“…While Phillips and colleagues (2018) provide novel insight into this field, nitric oxide (NO), historically known for its robust vasodilatory effects, has also been shown to blunt carotid chemoreceptor activity in preclinical and human models. For example, chronic supplementation of inorganic nitrate in the form of beetroot juice increases circulating NO bioavailability via the nitrate-nitrite-nitric oxide pathway, and has been show to attenuate carotid chemoreflex sensitivity (Bock et al 2018). While this study (Bock et al 2018) was not designed to investigate vascular function (e.g.…”

“…For example, chronic supplementation of inorganic nitrate in the form of beetroot juice increases circulating NO bioavailability via the nitrate-nitrite-nitric oxide pathway, and has been show to attenuate carotid chemoreflex sensitivity (Bock et al 2018). While this study (Bock et al 2018) was not designed to investigate vascular function (e.g. arterial stiffness, vasodilatation), it did provide compelling evidence to support the concept that carotid chemoreflex activity can be reduced in a healthy, older population by boosting NO bioavailability using a nutraceutical intervention.…”