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

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    Author
    Tonelli, A.R.
    Rogers, S.C.
    Doctor, A.
    Date
    2019
    Journal
    PLoS ONE
    Publisher
    Public Library of Science
    Type
    Article
    
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    https://doi.org/10.1371/journal.pone.0221777
    Abstract
    Rationale 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. Objectives 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. Findings 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). Conclusions 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. Copyright 2019 Tonelli et al.
    Keyword
    Nitric Oxide--pharmacokinetics
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85071443887&doi=10.1371%2fjournal.pone.0221777&partnerID=40&md5=5c16e3b2a26087c3d627bf66988346aa; http://hdl.handle.net/10713/10842
    ae974a485f413a2113503eed53cd6c53
    10.1371/journal.pone.0221777
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