K ATP channels modulate cerebral blood flow and oxygen delivery during isocapnic hypoxia in humans

• Published in: The Journal of physiology 2020-08, Vol.598 (16), p.3343-3356
• Main Authors: Rocha, Marcos P, Campos, Monique O, Mattos, João D, Mansur, Daniel E, Rocha, Helena N M, Secher, Niels H, Nóbrega, Antonio C L, Fernandes, Igor A
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate; Animals; Cerebrovascular Circulation; Hemodynamics; Humans; Hypoxia; Male; Oxygen
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/JP279751

ATP-sensitive K (K ) channels mediate hypoxia-induced cerebral vasodilatation and hyperperfusion in animals. We tested whether K channels blockade affects the increase in human cerebral blood flow (CBF) and the maintenance of oxygen delivery (CDO ) during hypoxia. Hypoxia-induced increases in the anterior circulation and total cerebral perfusion were attenuated under K channels blockade affecting the relative changes of brain oxygen delivery. Therefore, in humans, K channels activation modulates the vascular tone in the anterior circulation of the brain, contributing to CBF and CDO responses to hypoxia. ATP-sensitive K (K ) channels mediate hypoxia-induced cerebral vasodilatation and hyperperfusion in animals. We tested whether K channels blockade affects the increase in cerebral blood flow (CBF) and the maintenance of oxygen delivery (CDO ) during hypoxia in humans. Nine healthy men were exposed to 5-min trials of normoxia and isocapnic hypoxia (IHX, 10% O ) before (BGB) and 3 h after glibenclamide ingestion (AGB). Mean arterial pressure (MAP), arterial saturation ( ), partial pressure of oxygen ( ) and carbon dioxide ( ), internal carotid artery blood flow (ICABF), vertebral artery blood flow (VABF), total (t)CBF (Doppler ultrasound) and CDO were quantified during the trials. IHX provoked similar reductions in and , while MAP was not affected by oxygen desaturation or K blockade. A smaller increase in ICABF (ΔBGB: 36 ± 23 vs. ΔAGB 11 ± 18%, p = 0.019) but not in VABF (∆BGB 26 ± 21 vs. ∆AGB 27 ± 27%, p = 0.893) was observed during the hypoxic trial under K channels blockade. Thus, IHX-induced increases in tCBF (∆BGB 32 ± 19 vs. ∆AGB 14 ± 13%, p = 0.012) and CDO relative changes (∆BGB 7 ± 13 vs. ∆AGB -6 ± 14%, p = 0.048) were attenuated during the AGB hypoxic trial. In a separate protocol, 6 healthy men (5 from protocol 1) underwent a 5-min exposure to normoxia and IHX before and 3 h after placebo (5 mg of cornstarch) ingestion. IHX reduced and , but placebo did not affect the ICABF, VABF, tCBF, or CDO responses. Therefore, in humans, K channels activation modulates vascular tone in the anterior rather than the posterior circulation of the brain, contributing to tCBF and CDO responses to hypoxia.