Contribution of Flow-Dependent Vasomotor Mechanisms to the Autoregulation of Cerebral Blood Flow

Regulation of cerebral blood flow (CBF) is the result of multilevel mechanisms to maintain the appropriate blood supply to the brain while having to comply with the limited space available in the cranium. The latter requirement is ensured by the autoregulation of CBF, in which the pressure-sensitive myogenic response is known to play a pivotal role. However, in vivo increases in pressure are accompanied by increases in flow; yet the effects of flow on the vasomotor tone of cerebral vessels are less known. Earlier studies showed flow-sensitive dilation and/or constriction or both, but no clear picture emerged. Recently, the important role of flow-sensitive mechanism(s) eliciting the constriction of cerebral vessels has been demonstrated. This review focuses on the effect of hemodynamic forces (especially intraluminal flow) on the vasomotor tone of cerebral vessels and the underlying cellular and molecular mechanisms. A novel concept of autoregulation of CBF is proposed, suggesting that (in certain areas of the cerebrovascular tree) pressure- and flow-induced constrictions together maintain an effective autoregulation, and that alterations in these mechanisms may contribute to the development of cerebrovascular disorders. Future studies are warranted to explore the signals, the details of signaling processes and the in vivo importance of these mechanisms.