A pilot study on the kinetics of metabolites and microvascular cutaneous effects of nitric oxide inhalation in healthy volunteers

Inhaled nitric oxide (NO) exerts a variety of effects through metabolites and these play an important role in regulation of hemodynamics in the body. A detailed investigation into the generation of these metabolites has been overlooked. We investigated the kinetics of nitrite and S-nitrosothiol-hemo...

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Published in:PloS one 2019-08, Vol.14 (8), p.e0221777-e0221777
Main Authors: Tonelli, Adriano R, Aulak, Kulwant S, Ahmed, Mostafa K, Hausladen, Alfred, Abuhalimeh, Batool, Casa, Charlie J, Rogers, Stephen C, Timm, David, Doctor, Allan, Gaston, Benjamin, Dweik, Raed A
Format: Article
Language:English
Subjects:
Acetylcholine
Analysis
Biology and Life Sciences
Biomarkers
Chronic obstructive pulmonary disease
Critical care
FDA approval
Glycosylated hemoglobin
Health aspects
Healthy Volunteers
Hemodynamics
Hemoglobin
Hemoglobins
Humans
Hypoxia
Inflammation
Inhalation
Iontophoresis
Ischemia
Kinetics
Levels
Medicine
Medicine and Health Sciences
Metabolites
Metabolome
Microcirculation
Microvasculature
Microvessels - metabolism
Nitric oxide
Nitric Oxide - analysis
Nitrites
Nitrogen oxides
Pediatrics
Physical Sciences
Pilot Projects
Pulmonary hypertension
Respiration
Skin - blood supply
Traumatic brain injury
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cited_by cdi_FETCH-LOGICAL-c692t-461aef9ce8d110be54483ac43149831f4961132073fa0fe4d706548923d8183f3
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creator Tonelli, Adriano R
Aulak, Kulwant S
Ahmed, Mostafa K
Hausladen, Alfred
Abuhalimeh, Batool
Casa, Charlie J
Rogers, Stephen C
Timm, David
Doctor, Allan
Gaston, Benjamin
Dweik, Raed A
description Inhaled nitric oxide (NO) exerts a variety of effects through metabolites and these play an important role in regulation of hemodynamics in the body. A detailed investigation into the generation of these metabolites has been overlooked. We investigated the kinetics of nitrite and S-nitrosothiol-hemoglobin (SNO-Hb) in plasma derived from inhaled NO subjects and how this modifies the cutaneous microvascular response. We enrolled 15 healthy volunteers. Plasma nitrite levels at baseline and during NO inhalation (15 minutes at 40 ppm) were 102 (86-118) and 114 (87-129) nM, respectively. The nitrite peak occurred at 5 minutes of discontinuing NO (131 (104-170) nM). Plasma nitrate levels were not significantly different during the study. SNO-Hb molar ratio levels at baseline and during NO inhalation were 4.7E-3 (2.5E-3-5.8E-3) and 7.8E-3 (4.1E-3-13.0E-3), respectively. Levels of SNO-Hb continued to climb up to the last study time point (30 min: 10.6E-3 (5.3E-3-15.5E-3)). The response to acetylcholine iontophoresis both before and during NO inhalation was inversely associated with the SNO-Hb level (r: -0.57, p = 0.03, and r: -0.54, p = 0.04, respectively). Both nitrite and SNO-Hb increase during NO inhalation. Nitrite increases first, followed by a more sustained increase in Hb-SNO. Nitrite and Hb-SNO could be a mobile reservoir of NO with potential implications on the systemic microvasculature.
doi_str_mv 10.1371/journal.pone.0221777
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ispartof PloS one, 2019-08, Vol.14 (8), p.e0221777-e0221777
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1932-6203
language eng
recordid cdi_plos_journals_2282979687
source PubMed (Medline); Publicly Available Content Database
subjects Acetylcholine
Analysis
Biology and Life Sciences
Biomarkers
Chronic obstructive pulmonary disease
Critical care
FDA approval
Glycosylated hemoglobin
Health aspects
Healthy Volunteers
Hemodynamics
Hemoglobin
Hemoglobins
Humans
Hypoxia
Inflammation
Inhalation
Iontophoresis
Ischemia
Kinetics
Levels
Medicine
Medicine and Health Sciences
Metabolites
Metabolome
Microcirculation
Microvasculature
Microvessels - metabolism
Nitric oxide
Nitric Oxide - analysis
Nitrites
Nitrogen oxides
Pediatrics
Physical Sciences
Pilot Projects
Pulmonary hypertension
Respiration
Skin - blood supply
Traumatic brain injury
title A pilot study on the kinetics of metabolites and microvascular cutaneous effects of nitric oxide inhalation in healthy volunteers
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