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Sparse information is available on blood flow in the posterior part of the cerebral circulation (the vertebro-basilar system) during orthostatic stress (Haubrich et al. 2004; Sorond et al. 2005; Deegan et al. 2010). The vertebral artery (VA) and offshoots from the VA, including the anterior spinal and the posterior inferior cerebellar arteries, supply blood to the medulla oblongata, which is the location of important cardiac, vasomotor and respiratory control centres Alectinib clinical trial (Tatu et al. 1996). Many of the manifestations associated with development of presyncopal symptoms are likely to result from hypoperfusion in the vertebro-basilar system (Shin et al. 1999). Therefore, it is hypothesized that hypoperfusion of the medulla oblongata rather than the cerebral cortex during orthostatic stress could impair cardiac, vasomotor and respiratory control, possibly causing many of the haemodynamic changes that take place preceding syncope. Thus, blood flow regulation in the vertebro-basilar system is likely to be particularly important for orthostatic tolerance. Although the relative contribution of the internal carotid artery (ICA) and VA to global CBF at rest is believed to be balanced in resting humans (?75% in ICA and ?25% in VA, respectively), Sato & Sadamoto (2010) and Sato et al. (2011) reported that dynamic exercise evoked different blood flow responses in Osimertinib the internal carotid and vertebro-basilar systems. However, the effect of orthostatic stress on the distribution of blood flow in the ICA and VA remains unclear. There are anatomical and physiological differences between the internal carotid and vertebro-basilar GPX4 systems, including regional heterogeneity in the sympathetic innervation of intracranial arterioles (Edvinsson et al. 1976; Hamel et al. 1988) and cerebral CO2 reactivity (Sorond et al. 2005; Reinhard et al. 2008), which may lead to differences in the cerebrovascular responses to an orthostatic challenge. Studies have compared dynamic cerebral autoregulation (CA) during orthostatic stress between the internal carotid and vertebro-basilar system (Haubrich et al. 2004; Deegan et al. 2010). Haubrich et al. (2004) reported that dynamic CA evaluated using transfer function analysis (TFA) was less effective in the posterior cerebral artery (PCA) than in the MCA at rest and during HUT. In contrast, there appears to be no significant difference in dynamic CA between the MCA and VA during combined HUT and lower body negative pressure to presyncope in healthy subjects (Deegan et al. 2010). However, these previous studies used CBF velocity as an index of CBF using TCD measurement. Thus, the actual and global CBF response to orthostatic stress remains unknown but can be evaluated by determination of blood flow in the ICA and VA.