Early morning impairment in cerebral autoregulation and cerebrovascular CO2 reactivity in healthy humans: Relation to endothelial function

The reduction in cerebrovascular reactivity to CO₂ and/or endothelial function that occurs in the early hours after waking are potential causes for the increased risk for cardiovascular events at this time point. It is unknown whether cerebral autoregulation is reduced in the morning. We tested the hypothesis that early morning reduction in endothelium-dependent vascular reactivity would be linked to changes in cerebrovascular reactivity to CO ₂ and cerebral autoregulation (CA). Overnight changes in a dynamic cerebral autoregulation index (ARI) were determined from continuous recordings of blood flow velocity in the middle cerebral artery (MCAv) and arterial blood pressure (BP) during transiently induced hypotension in 20 individuals. Frontal cortical oxygenation (near infrared spectroscopy) and cerebral haemodynamics were also monitored during hypercapnia and before and during 3 min of active standing. Brachial artery flow-mediated endothelium-dependent vasodilatation (FMD) and endothelium-independent dilatation (NFMD) were also monitored. From evening to morning, there was a significant lowering in ARI (5.3 ± 0.5 versus 4.7 ± 0.6 a.u.; P < 0.05), cerebrovascular reactivity to CO₂ (5.3 ± 0.6 versus 4.6 ± 1.1% mmHg^-1; P < 0.05) and FMD (7.6 ± 0.9 versus 6.0 ± 1.4%; P < 0.05). The lowered FMD was related to the decrease in cerebrovascular reactivity to CO₂ (r = 0.76; P < 0.05). Transient reductions in morning MCAv and cortical oxyhaemoglobin concentrations were observed upon resuming a supine-to-upright position (P < 0.05 versus evening). The early morning reduction in cerebral autoregulation may facilitate the onset of cerebrovascular accidents; this may be of particular relevance to at-risk groups, especially upon resuming the upright position.