K<sub>ATP</sub> channels modulate cerebral blood flow and oxygen delivery during isocapnic hypoxia in humans
Marcos P. Rocha, Monique Opuszcka Campos, João D. Mattos, Daniel E. Mansur, Helena Rocha, Niels H. Secher, Antônio Cláudio Lucas da Nóbrega, Igor A. Fernandes
Abstract
Key points ATP‐sensitive K + (K ATP ) channels mediate hypoxia‐induced cerebral vasodilatation and hyperperfusion in animals. We tested whether K ATP channels blockade affects the increase in human cerebral blood flow (CBF) and the maintenance of oxygen delivery (CDO 2 ) during hypoxia. Hypoxia‐induced increases in the anterior circulation and total cerebral perfusion were attenuated under K ATP channels blockade affecting the relative changes of brain oxygen delivery. Therefore, in humans, K ATP channels activation modulates the vascular tone in the anterior circulation of the brain, contributing to CBF and CDO 2 responses to hypoxia. Abstract ATP‐sensitive K + (K ATP ) channels mediate hypoxia‐induced cerebral vasodilatation and hyperperfusion in animals. We tested whether K ATP channels blockade affects the increase in cerebral blood flow (CBF) and the maintenance of oxygen delivery (CDO 2 ) during hypoxia in humans. Nine healthy men were exposed to 5‐min trials of normoxia and isocapnic hypoxia (IHX, 10% O 2 ) 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 2 were quantified during the trials. IHX provoked similar reductions in and , while MAP was not affected by oxygen desaturation or K ATP 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 ATP channels blockade. Thus, IHX‐induced increases in tCBF (∆BGB 32 ± 19 vs . ∆AGB 14 ± 13%, p = 0.012) and CDO 2 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 2 responses. Therefore, in humans, K ATP channels activation modulates vascular tone in the anterior rather than the posterior circulation of the brain, contributing to tCBF and CDO 2 responses to hypoxia.