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The study of blood flow regulation is important to understand and resolve pathological conditions. As blood is a complex non‐Newtonian multiphase system, the foundations of blood rheological properties have been obtained mostly in viscometers. However, blood rheological behavior in vivo depends on red blood cells (RBCs) concentration, RBCs mechanical properties and RBC hydrodynamics, including the RBC migration away from the vessel wall in shear flow. This migration promotes the formation of a RBC depleted zone, or cell free layer (CFL), which reduces blood apparent viscosity. We hypothesize that perfusion pressure determines blood apparent viscosity in microvessels, as shear‐rate affects RBCs axial migration via influencing the CFL thickness. This study analyzes the effects of perfusion pressure on blood flow in individual arterioles within the rat cremaster muscle preparation. Perfusion pressures to this microvascular bed were controlled by occlusions of the iliac artery using a pressure cuff. Blood flow measurements were obtained from direct measurements of blood flow velocity field, as well as CFL thickness determination using intra‐vital microscopy. Our results indicate that perfusion pressure determines shear‐rates and the CFL thickness and its variations. In addition, blood flow reduction increased local vascular resistance via augmenting blood apparent viscosity rather than vascular hindrance. In conclusion, blood rheology could act as an intrinsic mechanism to further limit blood flow to tissue with limited myogenic and metabolic responses at low perfusion pressures.
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