K(Atp)Channels Modulate Cerebral Blood Flow And Oxygen Delivery During Isocapnic Hypoxia In Humans

Key pointsATP-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 (CDO2) 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. 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 (CDO2) 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 (SaO2), partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2), 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 inSaO2andPaO2, while MAP was not affected by oxygen desaturation or K(ATP)blockade. A smaller increase in ICABF (Delta BGB: 36 +/- 23vs. Delta AGB 11 +/- 18%,p = 0.019) but not in VABF ( increment BGB 26 +/- 21vs. increment AGB 27 +/- 27%,p = 0.893) was observed during the hypoxic trial under K(ATP)channels blockade. Thus, IHX-induced increases in tCBF ( increment BGB 32 +/- 19vs. increment AGB 14 +/- 13%,p = 0.012) and CDO(2)relative changes ( increment BGB 7 +/- 13vs. increment 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 reducedSaO2andPaO2, 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.