Abstract We examined the impact of progressive hypotension with and without hypocapnia on regional extracranial cerebral blood flow (CBF) and intracranial velocities. Participants underwent progressive lower-body negative pressure (LBNP) until pre-syncope to inflict hypotension. End-tidal carbon dioxide was clamped at baseline levels (isocapnic trial) or uncontrolled (poikilocapnic trial). Middle cerebral artery (MCA) and posterior cerebral artery (PCA) blood velocities (transcranial Doppler; TCD), heart rate, blood pressure and end-tidal carbon dioxide were obtained continuously. Measurements of internal carotid artery (ICA) and vertebral artery (VA) blood flow (ICA BF and VA BF respectively) were also obtained. Overall, blood pressure was reduced by ∼20 % from baseline in both trials (P < 0.001). In the isocapnic trial, end-tidal carbon dioxide was successfully clamped at baseline with hypotension, whereas in the poikilocapnic trial it was reduced by 11.1 mmHg (P < 0.001) with hypotension. The decline in the ICA BF with hypotension was comparable between trials (−139 + − 82 ml; ∼30 %; P < 0.0001); however, the decline in the VA BF was −28 + − 22 ml/min (∼21 %) greater in the poikilocapnic trial compared with the isocapnic trial (P = 0.002). Regardless of trial, the blood flow reductions in ICA (−26 + − 14 %) and VA (−27 + − 14 %) were greater than the decline in MCA (−21 + − 15 %) and PCA (−19 + − 10 %) velocities respectively (P 0.01). Significant reductions in the diameter of both the ICA (∼5 %) and the VA (∼7 %) contributed to the decline in cerebral perfusion with systemic hypotension, independent of hypocapnia. In summary, our findings indicate that blood flow in the VA, unlike the ICA, is sensitive to changes hypotension and hypocapnia. We show for the first time that the decline in global CBF with hypotension is influenced by arterial constriction in the ICA and VA. Additionally, our findings suggest TCD measures of blood flow velocity may modestly underestimate changes in CBF during hypotension with and without hypocapnia, particularly in the posterior circulation
