Cholinergic control of the cerebral vasculature in humans

Key points • Cerebral autoregulation maintains cerebral perfusion relatively constant in the face of slow changes in arterial pressure, but is less effective against more rapid changes (i.e. functions as a ‘high‐pass’ filter). • While thought to be maintained mainly through myogenic adjustments to changes in transmural pressure, recent work has highlighted a possibility of active autonomic involvement in cerebral autoregulation. • In this study we examined the cerebrovascular effects of cholinergic blockade on nine healthy volunteers during the application of oscillatory lower body pressure at six frequencies from 0.03 to 0.08 Hz. • Cholinergic blockade impaired autoregulation at frequencies above 0.04 Hz, suggesting a role for active cholinergic vasodilatation in the maintenance of cerebral perfusion. Despite growing evidence of autonomic nervous system involvement in the regulation of cerebral blood flow, the specific contribution of cholinergic vasodilatation to cerebral autoregulation remains unknown. We examined cerebral and forearm blood flow responses to augmented arterial pressure oscillations with and without cholinergic blockade. Oscillatory lower body negative pressure was applied at six frequencies from 0.03 to 0.08 Hz in nine healthy subjects with and without cholinergic blockade via glycopyrrolate. Cholinergic blockade increased cross‐spectral coherence between arterial pressure and cerebral flow at all frequencies except 0.03 Hz and increased the transfer function gain at frequencies above 0.05 Hz. In contrast, gain between pressure and forearm flow increased only at frequencies below 0.06 Hz. These data demonstrate that the cholinergic system plays an active and unique role in cerebral autoregulation. The frequency region and magnitude of effect is very similar to what has been seen with sympathetic blockade, indicating a possible balance between the two reflexes to most effectively respond to rising and falling pressure. These findings might have implications for the role of dysfunction in autonomic control of the vasculature in cerebrovascular disease states.