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Hemoglobin and cerebral hypoxic vasodilation in humans: Evidence for nitric oxide-dependent and S-nitrosothiol mediated signal transduction

Cerebral hypoxic vasodilation is poorly understood in humans, which undermines the development of therapeutics to optimize cerebral oxygen delivery. Across four investigations (total n = 195) we investigated the role of nitric oxide (NO) and hemoglobin-based S-nitrosothiol (RSNO) and nitrite ( [Form...

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Autores principales: Hoiland, Ryan L, MacLeod, David B, Stacey, Benjamin S, Caldwell, Hannah G, Howe, Connor A, Nowak-Flück, Daniela, Carr, Jay MJR, Tymko, Michael M, Coombs, Geoff B, Patrician, Alexander, Tremblay, Joshua C, Van Mierlo, Michelle, Gasho, Chris, Stembridge, Mike, Sekhon, Mypinder S, Bailey, Damian M, Ainslie, Philip N
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10414015/
https://www.ncbi.nlm.nih.gov/pubmed/37042194
http://dx.doi.org/10.1177/0271678X231169579
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author Hoiland, Ryan L
MacLeod, David B
Stacey, Benjamin S
Caldwell, Hannah G
Howe, Connor A
Nowak-Flück, Daniela
Carr, Jay MJR
Tymko, Michael M
Coombs, Geoff B
Patrician, Alexander
Tremblay, Joshua C
Van Mierlo, Michelle
Gasho, Chris
Stembridge, Mike
Sekhon, Mypinder S
Bailey, Damian M
Ainslie, Philip N
author_facet Hoiland, Ryan L
MacLeod, David B
Stacey, Benjamin S
Caldwell, Hannah G
Howe, Connor A
Nowak-Flück, Daniela
Carr, Jay MJR
Tymko, Michael M
Coombs, Geoff B
Patrician, Alexander
Tremblay, Joshua C
Van Mierlo, Michelle
Gasho, Chris
Stembridge, Mike
Sekhon, Mypinder S
Bailey, Damian M
Ainslie, Philip N
author_sort Hoiland, Ryan L
collection PubMed
description Cerebral hypoxic vasodilation is poorly understood in humans, which undermines the development of therapeutics to optimize cerebral oxygen delivery. Across four investigations (total n = 195) we investigated the role of nitric oxide (NO) and hemoglobin-based S-nitrosothiol (RSNO) and nitrite ( [Formula: see text] ) signaling in the regulation of cerebral hypoxic vasodilation. We conducted hemodilution (n = 10) and NO synthase inhibition experiments (n = 11) as well as hemoglobin oxygen desaturation protocols, wherein we measured cerebral blood flow (CBF), intra-arterial blood pressure, and in subsets of participants trans-cerebral release/uptake of RSNO and [Formula: see text] . Higher CBF during hypoxia was associated with greater trans-cerebral RSNO release but not [Formula: see text] , while NO synthase inhibition reduced cerebral hypoxic vasodilation. Hemodilution increased the magnitude of cerebral hypoxic vasodilation following acute hemodilution, while in 134 participants tested under normal conditions, hypoxic cerebral vasodilation was inversely correlated to arterial hemoglobin concentration. These studies were replicated in a sample of polycythemic high-altitude native Andeans suffering from excessive erythrocytosis (n = 40), where cerebral hypoxic vasodilation was inversely correlated to hemoglobin concentration, and improved with hemodilution (n = 6). Collectively, our data indicate that cerebral hypoxic vasodilation is partially NO-dependent, associated with trans-cerebral RSNO release, and place hemoglobin-based NO signaling as a central mechanism of cerebral hypoxic vasodilation in humans.
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spelling pubmed-104140152023-08-11 Hemoglobin and cerebral hypoxic vasodilation in humans: Evidence for nitric oxide-dependent and S-nitrosothiol mediated signal transduction Hoiland, Ryan L MacLeod, David B Stacey, Benjamin S Caldwell, Hannah G Howe, Connor A Nowak-Flück, Daniela Carr, Jay MJR Tymko, Michael M Coombs, Geoff B Patrician, Alexander Tremblay, Joshua C Van Mierlo, Michelle Gasho, Chris Stembridge, Mike Sekhon, Mypinder S Bailey, Damian M Ainslie, Philip N J Cereb Blood Flow Metab Original Articles Cerebral hypoxic vasodilation is poorly understood in humans, which undermines the development of therapeutics to optimize cerebral oxygen delivery. Across four investigations (total n = 195) we investigated the role of nitric oxide (NO) and hemoglobin-based S-nitrosothiol (RSNO) and nitrite ( [Formula: see text] ) signaling in the regulation of cerebral hypoxic vasodilation. We conducted hemodilution (n = 10) and NO synthase inhibition experiments (n = 11) as well as hemoglobin oxygen desaturation protocols, wherein we measured cerebral blood flow (CBF), intra-arterial blood pressure, and in subsets of participants trans-cerebral release/uptake of RSNO and [Formula: see text] . Higher CBF during hypoxia was associated with greater trans-cerebral RSNO release but not [Formula: see text] , while NO synthase inhibition reduced cerebral hypoxic vasodilation. Hemodilution increased the magnitude of cerebral hypoxic vasodilation following acute hemodilution, while in 134 participants tested under normal conditions, hypoxic cerebral vasodilation was inversely correlated to arterial hemoglobin concentration. These studies were replicated in a sample of polycythemic high-altitude native Andeans suffering from excessive erythrocytosis (n = 40), where cerebral hypoxic vasodilation was inversely correlated to hemoglobin concentration, and improved with hemodilution (n = 6). Collectively, our data indicate that cerebral hypoxic vasodilation is partially NO-dependent, associated with trans-cerebral RSNO release, and place hemoglobin-based NO signaling as a central mechanism of cerebral hypoxic vasodilation in humans. SAGE Publications 2023-04-12 2023-09 /pmc/articles/PMC10414015/ /pubmed/37042194 http://dx.doi.org/10.1177/0271678X231169579 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Articles
Hoiland, Ryan L
MacLeod, David B
Stacey, Benjamin S
Caldwell, Hannah G
Howe, Connor A
Nowak-Flück, Daniela
Carr, Jay MJR
Tymko, Michael M
Coombs, Geoff B
Patrician, Alexander
Tremblay, Joshua C
Van Mierlo, Michelle
Gasho, Chris
Stembridge, Mike
Sekhon, Mypinder S
Bailey, Damian M
Ainslie, Philip N
Hemoglobin and cerebral hypoxic vasodilation in humans: Evidence for nitric oxide-dependent and S-nitrosothiol mediated signal transduction
title Hemoglobin and cerebral hypoxic vasodilation in humans: Evidence for nitric oxide-dependent and S-nitrosothiol mediated signal transduction
title_full Hemoglobin and cerebral hypoxic vasodilation in humans: Evidence for nitric oxide-dependent and S-nitrosothiol mediated signal transduction
title_fullStr Hemoglobin and cerebral hypoxic vasodilation in humans: Evidence for nitric oxide-dependent and S-nitrosothiol mediated signal transduction
title_full_unstemmed Hemoglobin and cerebral hypoxic vasodilation in humans: Evidence for nitric oxide-dependent and S-nitrosothiol mediated signal transduction
title_short Hemoglobin and cerebral hypoxic vasodilation in humans: Evidence for nitric oxide-dependent and S-nitrosothiol mediated signal transduction
title_sort hemoglobin and cerebral hypoxic vasodilation in humans: evidence for nitric oxide-dependent and s-nitrosothiol mediated signal transduction
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10414015/
https://www.ncbi.nlm.nih.gov/pubmed/37042194
http://dx.doi.org/10.1177/0271678X231169579
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