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