Torsional Force by Helical Pericytes Regulates Blood Flow in Downstream Capillaries

This study investigates the contractile properties of downstream capillaries, which are traditionally regarded as passive conduits, and addresses ongoing debates surrounding blood flow regulation. It is widely accepted that these capillaries passively dilate in response to increased blood flow in upstream microvessels, and that the helical pericytes located on them lack contractile capability, largely due to the absence of detectable -SMA expression. Challenging this prevailing view, we demonstrate that downstream capillary pericytes do express both -SMA and Myosin11, as shown using in situ hybridization on whole-mount intact retinas--unlike prior studies that relied on dissociated cells. Furthermore, Forster resonance energy transfer (FRET) analysis reveals that -SMA and Myosin11 are in sufficiently close proximity to permit actomyosin bridge cycling, a process essential for contraction. We also show that pericyte contraction can be inhibited by disrupting this molecular interaction. Distinct from the nodal constrictions caused by circular pericyte processes in upstream microvessels, we identify torsional contractions in the downstream capillaries in the retina of living mice using two-photon laser scanning microscopy (TPLSM), which regulates blood flow. These contractions provide direct evidence that downstream capillaries actively contribute to blood flow regulation. Notably, such contractions were overlooked in previous TPLSM studies that monitored only luminal diameter, unless the specialized analytical techniques we employed were applied. Our 3D modeling confirms that these torsional contractions correlate with the helical morphology of pericytes in downstream capillaries--a structure previously thought incapable of producing significant constrictive force. In conclusion, our findings provide direct evidence that downstream pericytes play an active role in regulating blood flow. They highlight a previously unrecognized mechanism--torsional contraction--that aligns with the helical structure of these pericytes and contributes to flow regulation in small-caliber capillaries located nearest to regions of high oxygen demand. TEASERDownstream Capillary Pericytes Express -SMA and Regulate Flow via Torsional Contraction