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We investigated the influence of arterial P C O 2 ( P aC O 2 ) with and without acutely elevated arterial pH and bicarbonate ([HCO ]) on cerebral blood flow (CBF) regulation in the internal carotid artery and vertebral artery. We assessed stepwise iso-oxic alterations in P aC O 2 (i.e. cerebrovascular CO reactivity) prior to and following i.v. sodium bicarbonate infusion (NaHCO ) to acutely elevate arterial pH and [HCO ]. Total CBF was unchanged irrespective of a higher arterial pH at each matched stage of P aC O 2 , indicating that CBF is