Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1785087253969633280 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10414015 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT hoilandryanl hemoglobinandcerebralhypoxicvasodilationinhumansevidencefornitricoxidedependentandsnitrosothiolmediatedsignaltransduction AT macleoddavidb hemoglobinandcerebralhypoxicvasodilationinhumansevidencefornitricoxidedependentandsnitrosothiolmediatedsignaltransduction AT staceybenjamins hemoglobinandcerebralhypoxicvasodilationinhumansevidencefornitricoxidedependentandsnitrosothiolmediatedsignaltransduction AT caldwellhannahg hemoglobinandcerebralhypoxicvasodilationinhumansevidencefornitricoxidedependentandsnitrosothiolmediatedsignaltransduction AT howeconnora hemoglobinandcerebralhypoxicvasodilationinhumansevidencefornitricoxidedependentandsnitrosothiolmediatedsignaltransduction AT nowakfluckdaniela hemoglobinandcerebralhypoxicvasodilationinhumansevidencefornitricoxidedependentandsnitrosothiolmediatedsignaltransduction AT carrjaymjr hemoglobinandcerebralhypoxicvasodilationinhumansevidencefornitricoxidedependentandsnitrosothiolmediatedsignaltransduction AT tymkomichaelm hemoglobinandcerebralhypoxicvasodilationinhumansevidencefornitricoxidedependentandsnitrosothiolmediatedsignaltransduction AT coombsgeoffb hemoglobinandcerebralhypoxicvasodilationinhumansevidencefornitricoxidedependentandsnitrosothiolmediatedsignaltransduction AT patricianalexander hemoglobinandcerebralhypoxicvasodilationinhumansevidencefornitricoxidedependentandsnitrosothiolmediatedsignaltransduction AT tremblayjoshuac hemoglobinandcerebralhypoxicvasodilationinhumansevidencefornitricoxidedependentandsnitrosothiolmediatedsignaltransduction AT vanmierlomichelle hemoglobinandcerebralhypoxicvasodilationinhumansevidencefornitricoxidedependentandsnitrosothiolmediatedsignaltransduction AT gashochris hemoglobinandcerebralhypoxicvasodilationinhumansevidencefornitricoxidedependentandsnitrosothiolmediatedsignaltransduction AT stembridgemike hemoglobinandcerebralhypoxicvasodilationinhumansevidencefornitricoxidedependentandsnitrosothiolmediatedsignaltransduction AT sekhonmypinders hemoglobinandcerebralhypoxicvasodilationinhumansevidencefornitricoxidedependentandsnitrosothiolmediatedsignaltransduction AT baileydamianm hemoglobinandcerebralhypoxicvasodilationinhumansevidencefornitricoxidedependentandsnitrosothiolmediatedsignaltransduction AT ainsliephilipn hemoglobinandcerebralhypoxicvasodilationinhumansevidencefornitricoxidedependentandsnitrosothiolmediatedsignaltransduction |