title: Increased consumption and vasodilatory effect of nitrite during exercise.
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.
authors.affiliation: Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, Maryland;
authors.forename: Yuen Yi
authors.initials: YY
authors.lastname: Hon
authors.affiliation: Vascular Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland;
authors.forename: Elaina E
authors.initials: EE
authors.lastname: Lin
authors.affiliation: Office of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland;
authors.forename: Xin
authors.initials: X
authors.lastname: Tian
authors.affiliation: Office of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland;
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, People's Republic of China;
authors.forename: He
authors.initials: H
authors.lastname: Sun
authors.affiliation: Division of Pulmonary and Critical Care Medicine, VA Puget Sound Health Care System, University of Washington, Seattle, Washington; and.
authors.forename: Erik R
authors.initials: ER
authors.lastname: Swenson
authors.affiliation: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
authors.forename: Angelo M
authors.initials: AM
authors.lastname: Taveira-Dasilva
authors.affiliation: Vascular Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland;
authors.forename: Mark T
authors.initials: MT
authors.lastname: Gladwin
authors.affiliation: Vascular Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland; machador@uic.edu.
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Machado
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D009573:Nitrites / Q000378:metabolism*; D012977:Sodium Nitrite / Q000008:administration & dosage / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D009573:Nitrites; D012977:Sodium Nitrite
keywords: hemodynamics; incremental exercise test; nitrite store; pharmacokinetics; vasodilation