Increased consumption and vasodilatory effect of nitrite during exercise

Yuen Yi Hon, Elaina E. Lin, Xin Tian, Yang Yang, He Sun, Erik R. Swenson, Angelo M. Taveira-Dasilva, Mark T. Gladwin, Roberto Machado

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

This study investigated the effects of aerobic-to-anaerobic exercise on nitrite stores in the human circulation and evaluated the effects of systemic nitrite infusion on aerobic and anaerobic exercise capacity and hemodynamics. Six healthy volunteers were randomized to receive sodium nitrite or saline for 70 min in two separate occasions in an exercise study. Subjects cycled on an upright electronically braked cycle ergometer 30 min into the infusion according to a ramp protocol designed to attain exhaustion in 10 min. They were allowed to recover for 30 min thereafter. The changes of whole blood nitrite concentrations over the 70-min study period were analyzed by pharmacokinetic modeling. Longitudinal measurements of hemodynamic and clinical variables were analyzed by fitting nonparametric regression spline models. During exercise, nitrite consumption/elimination rate was increased by ∼137%. Cardiac output (CO), mean arterial pressure (MAP), and pulmonary artery pressure (PAP) were increased, but smaller elevation of MAP and larger increases of CO and PAP were found during nitrite infusion compared with placebo control. The higher CO and lower MAP during nitrite infusion were likely attributed to vasodilation and a trend toward decrease in systemic vascular resistance. In contrast, there were no significant changes in mean pulmonary artery pressures and pulmonary vascular resistance. These findings, together with the increased consumption of nitrite and production of iron-nitrosyl-hemoglobin during exercise, support the notion of nitrite conversion to release NO resulting in systemic vasodilatation. However, at the dosing used in this protocol achieving micromolar plasma concentrations of nitrite, exercise capacity was not enhanced, as opposed to other reports using lower dosing.

Original languageEnglish (US)
Pages (from-to)L354-L364
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume310
Issue number4
DOIs
StatePublished - Feb 15 2016
Externally publishedYes

Fingerprint

Nitrites
Exercise
Pulmonary Artery
Arterial Pressure
Pressure
Vasodilation
Cardiac Output
Vascular Resistance
Hemodynamics
High Cardiac Output
Sodium Nitrite
Architectural Accessibility
Healthy Volunteers
Pharmacokinetics
Placebos

Keywords

  • Hemodynamics
  • Incremental exercise test
  • Nitrite store
  • Pharmacokinetics
  • Vasodilation

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Increased consumption and vasodilatory effect of nitrite during exercise. / Hon, Yuen Yi; Lin, Elaina E.; Tian, Xin; Yang, Yang; Sun, He; Swenson, Erik R.; Taveira-Dasilva, Angelo M.; Gladwin, Mark T.; Machado, Roberto.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 310, No. 4, 15.02.2016, p. L354-L364.

Research output: Contribution to journalArticle

Hon, YY, Lin, EE, Tian, X, Yang, Y, Sun, H, Swenson, ER, Taveira-Dasilva, AM, Gladwin, MT & Machado, R 2016, 'Increased consumption and vasodilatory effect of nitrite during exercise', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 310, no. 4, pp. L354-L364. https://doi.org/10.1152/ajplung.00081.2015
Hon, Yuen Yi ; Lin, Elaina E. ; Tian, Xin ; Yang, Yang ; Sun, He ; Swenson, Erik R. ; Taveira-Dasilva, Angelo M. ; Gladwin, Mark T. ; Machado, Roberto. / Increased consumption and vasodilatory effect of nitrite during exercise. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2016 ; Vol. 310, No. 4. pp. L354-L364.
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AB - This study investigated the effects of aerobic-to-anaerobic exercise on nitrite stores in the human circulation and evaluated the effects of systemic nitrite infusion on aerobic and anaerobic exercise capacity and hemodynamics. Six healthy volunteers were randomized to receive sodium nitrite or saline for 70 min in two separate occasions in an exercise study. Subjects cycled on an upright electronically braked cycle ergometer 30 min into the infusion according to a ramp protocol designed to attain exhaustion in 10 min. They were allowed to recover for 30 min thereafter. The changes of whole blood nitrite concentrations over the 70-min study period were analyzed by pharmacokinetic modeling. Longitudinal measurements of hemodynamic and clinical variables were analyzed by fitting nonparametric regression spline models. During exercise, nitrite consumption/elimination rate was increased by ∼137%. Cardiac output (CO), mean arterial pressure (MAP), and pulmonary artery pressure (PAP) were increased, but smaller elevation of MAP and larger increases of CO and PAP were found during nitrite infusion compared with placebo control. The higher CO and lower MAP during nitrite infusion were likely attributed to vasodilation and a trend toward decrease in systemic vascular resistance. In contrast, there were no significant changes in mean pulmonary artery pressures and pulmonary vascular resistance. These findings, together with the increased consumption of nitrite and production of iron-nitrosyl-hemoglobin during exercise, support the notion of nitrite conversion to release NO resulting in systemic vasodilatation. However, at the dosing used in this protocol achieving micromolar plasma concentrations of nitrite, exercise capacity was not enhanced, as opposed to other reports using lower dosing.

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