Contractile Pericytes Determine the Direction of Blood Flow at Capillary Bifurcations

Pericytes cover most of the surface area of brain capillaries, and yet their role in controlling cerebral blood flow is controversial. Although pericytes have a distinct morphology from vascular smooth muscle, pericytes at the first and second capillary junctions downstream of the terminal arteriole exhibit many of the same excitation‐contraction coupling molecules as smooth muscle, e.g. smooth muscle a‐actin, Ca v 1.2 and TRPM4 (from immunohistochemistry). We tested the hypothesis that junctional pericytes are capable of controlling the direction of flow in the capillary bed, insuring efficient delivery of blood to downstream neurons. Using a novel transgenic mouse expressing a genetically encoded Ca 2+ biosensor in contractile pericytes and smooth muscle (acta2‐GCaMP5‐mCherry), we observed IP 3 R‐ and Ca v 1.2‐, but not ryanodine receptor‐mediated, Ca 2+ events. Using in vivo multiphoton microscopy, we observed a higher frequency of Ca 2+ events in pericyte projections covering the branch with lower red blood cell (RBC) flux at capillary bifurcation. The thromboxane receptor agonist, U46619, deferentially increased Ca 2+ signaling in the pericytes covering the two branches such that less contracted branch increased its Ca 2+ signaling and RBC flux was reduced to the level of other branch, i.e. flux was normalized in two branches. These data support the concept that pericytes play a role in controlling the directional flow of blood within the capillary bed. Support or Funding Information Totman Medical Research Trust, Foundation Leducq, AHA 14POST20480144, NIH T32HL‐007594, P01HL‐095488, R37DK‐053832, R01HL‐121706, and R24HL‐120847