Endothelial Piezo1 channel controls cerebral blood flow

Abstract

Cerebral blood flow is controlled to meet the ever-changing demands of active neurons. Brain capillaries are equipped with sensors of neurovascular coupling agents released from neurons/astrocytes onto the outer wall of a capillary. While capillaries can translate external signals into electrical and Ca2+ changes, control mechanisms from the lumen are less clear. The continuous flux of red blood cells and plasma through narrow-diameter capillaries imposes mechanical forces on the luminal (inner) capillary wall. We have recently discovered that the mechanosensitive Piezo1 channels operate as mechanosensors in CNS capillaries. Whether—and if so how—Piezo1-mediated mechanosensation regulates CBF is not known. Using genetically engineered mice in which endothelial Piezo1 is ablated (Piezo1 EC-KO ) or mutated (Piezo1 EC-mut ), we assessed channel activity and CBF. We provide evidence that Piezo1 plays an important role in CBF control and profoundly affects functional hyperemia during somatosensory stimulation. These observations are of profound significance for the control of brain blood flow in health and in disorders where hemodynamic forces are disrupted, such as hypertension. The American Heart Association (20CDA35310097), the National Institute of General Medical Sciences (P20GM135007), the Totman Medical Research Trust, the Larner College of Medicine, University of Vermont, and the Cardiovascular Research Institute of Vermont. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.