Cerebral autoregulation in humans: role of the cholinergic mechanisms

Abstract

Cholinergic mechanisms in cerebral autoregulation remain poorly characterized. However, there is some evidence for a cholinergic role. For example, cholinesterase inhibitors improve cerebral blood flow and cerebrovascular reactivity in Alzheimer patients who respond to treatment. Therefore we examined cerebral blood flow responses to augmented arterial pressure oscillations with and without cholinergic blockade. Oscillatory lower body negative pressure (OLBNP) was used at six frequencies from 0.03 to 0.08 Hz in 9 healthy subjects with and without cholinergic blockade via glycopyrrolate. Cholinergic blockade resulted in an increase in mean blood pressure and heart rate, but had no effect on cerebral flow. The transfer function relationship to arterial pressure at frequencies greater than 0.05 Hz were significantly increased (Coherence: 0.740±0.061 vs. 0.908±0.052, Gain: 0.668±0.070 vs. 0.962±0.027 at 0.08 Hz), but both the coherence and gain of the relation remained weak at the lowest frequencies in the cerebral circulation. Our data demonstrate a strong, frequency dependent role for cholinergic regulation of blood flow in the cerebrovasculature. However, the frequency dependence is similar to the sympathetic system, and thus the two mechanisms may have complimentary or redundant roles in autoregulation.