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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

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 Grace; Howe, Connor A; Nowak-Flück, Daniela; Carr, Jay M J R; 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.

In: Journal of Cerebral Blood Flow and Metabolism, 12.04.2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Hoiland, RL, MacLeod, DB, Stacey, BS, Caldwell, HG, Howe, CA, Nowak-Flück, D, Carr, JMJR, Tymko, MM, Coombs, GB, Patrician, A, Tremblay, JC, Van Mierlo, M, Gasho, C, Stembridge, M, Sekhon, MS, Bailey, DM & Ainslie, PN 2023, 'Hemoglobin and cerebral hypoxic vasodilation in humans: Evidence for nitric oxide-dependent and S-nitrosothiol mediated signal transduction', Journal of Cerebral Blood Flow and Metabolism. https://doi.org/10.1177/0271678X231169579

APA

Hoiland, R. L., MacLeod, D. B., Stacey, B. S., Caldwell, H. G., Howe, C. A., Nowak-Flück, D., Carr, J. M. J. R., Tymko, M. M., Coombs, G. B., Patrician, A., Tremblay, J. C., Van Mierlo, M., Gasho, C., Stembridge, M., Sekhon, M. S., Bailey, D. M., & Ainslie, P. N. (2023). Hemoglobin and cerebral hypoxic vasodilation in humans: Evidence for nitric oxide-dependent and S-nitrosothiol mediated signal transduction. Journal of Cerebral Blood Flow and Metabolism. https://doi.org/10.1177/0271678X231169579

Vancouver

Hoiland RL, MacLeod DB, Stacey BS, Caldwell HG, Howe CA, Nowak-Flück D et al. Hemoglobin and cerebral hypoxic vasodilation in humans: Evidence for nitric oxide-dependent and S-nitrosothiol mediated signal transduction. Journal of Cerebral Blood Flow and Metabolism. 2023 Apr 12. https://doi.org/10.1177/0271678X231169579

Author

Hoiland, Ryan L ; MacLeod, David B ; Stacey, Benjamin S ; Caldwell, Hannah Grace ; Howe, Connor A ; Nowak-Flück, Daniela ; Carr, Jay M J R ; 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. In: Journal of Cerebral Blood Flow and Metabolism. 2023.

Bibtex

@article{be02e8baa9fc4268ba2124a84b6413de,
title = "Hemoglobin and cerebral hypoxic vasodilation in humans: Evidence for nitric oxide-dependent and S-nitrosothiol mediated signal transduction",
abstract = "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 (NO2-) 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 NO2-. Higher CBF during hypoxia was associated with greater trans-cerebral RSNO release but not NO2-, 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. ",
keywords = "Faculty of Science, Cerebral blood flow, Hemoglobin, Hypoxia, Nitric oxide, Oxygen delivery",
author = "Hoiland, {Ryan L} and MacLeod, {David B} and Stacey, {Benjamin S} and Caldwell, {Hannah Grace} and Howe, {Connor A} and Daniela Nowak-Fl{\"u}ck and Carr, {Jay M J R} and Tymko, {Michael M} and Coombs, {Geoff B} and Alexander Patrician and Tremblay, {Joshua C} and {Van Mierlo}, Michelle and Chris Gasho and Mike Stembridge and Sekhon, {Mypinder S} and Bailey, {Damian M} and Ainslie, {Philip N}",
note = "(Ekstern)",
year = "2023",
month = apr,
day = "12",
doi = "10.1177/0271678X231169579",
language = "English",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "SAGE Publications",

}

RIS

TY - JOUR

T1 - Hemoglobin and cerebral hypoxic vasodilation in humans: Evidence for nitric oxide-dependent and S-nitrosothiol mediated signal transduction

AU - Hoiland, Ryan L

AU - MacLeod, David B

AU - Stacey, Benjamin S

AU - Caldwell, Hannah Grace

AU - Howe, Connor A

AU - Nowak-Flück, Daniela

AU - Carr, Jay M J R

AU - Tymko, Michael M

AU - Coombs, Geoff B

AU - Patrician, Alexander

AU - Tremblay, Joshua C

AU - Van Mierlo, Michelle

AU - Gasho, Chris

AU - Stembridge, Mike

AU - Sekhon, Mypinder S

AU - Bailey, Damian M

AU - Ainslie, Philip N

N1 - (Ekstern)

PY - 2023/4/12

Y1 - 2023/4/12

N2 - 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 (NO2-) 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 NO2-. Higher CBF during hypoxia was associated with greater trans-cerebral RSNO release but not NO2-, 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.

AB - 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 (NO2-) 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 NO2-. Higher CBF during hypoxia was associated with greater trans-cerebral RSNO release but not NO2-, 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.

KW - Faculty of Science

KW - Cerebral blood flow

KW - Hemoglobin

KW - Hypoxia

KW - Nitric oxide

KW - Oxygen delivery

U2 - 10.1177/0271678X231169579

DO - 10.1177/0271678X231169579

M3 - Journal article

C2 - 37042194

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

ER -

ID: 343300443