Contractile pericytes determine the direction of blood flow at capillary junctions

Significance Capillaries—the most abundant vessels in the circulatory system—deliver O2 and nutrients to all cells of the body. In the brain and retina, capillaries also act as a sensory web that detects neuronal activity. Here, we demonstrate that pericytes localized at capillary junctions in a postarteriole transitional region possess unique properties, notably including contractility, that enable them to dynamically manipulate capillary branch diameters and exert fine control over the distribution of blood within the capillary network. In so doing, these contractile junctional pericytes fine tune the delivery of O2 and nutrients and thus serve to meet the specific needs of neurons. Given these unique properties, pericytes represent a therapeutic target for cardiovascular and neurodegenerative diseases. The essential function of the circulatory system is to continuously and efficiently supply the O2 and nutrients necessary to meet the metabolic demands of every cell in the body, a function in which vast capillary networks play a key role. Capillary networks serve an additional important function in the central nervous system: acting as a sensory network, they detect neuronal activity in the form of elevated extracellular K+ and initiate a retrograde, propagating, hyperpolarizing signal that dilates upstream arterioles to rapidly increase local blood flow. Yet, little is known about how blood entering this network is distributed on a branch-to-branch basis to reach specific neurons in need. Here, we demonstrate that capillary-enwrapping projections of junctional, contractile pericytes within a postarteriole transitional region differentially constrict to structurally and dynamically determine the morphology of capillary junctions and thereby regulate branch-specific blood flow. We further found that these contractile pericytes are capable of receiving propagating K+-induced hyperpolarizing signals propagating through the capillary network and dynamically channeling red blood cells toward the initiating signal. By controlling blood flow at junctions, contractile pericytes within a functionally distinct postarteriole transitional region maintain the efficiency and effectiveness of the capillary network, enabling optimal perfusion of the brain.