EXPRESS: Increases in Intraluminal Viscosity Disrupt Microvascular Flow Dynamics

Autoregulation of blood flow relies on a balance between pressure-induced constriction and shear stress-mediated dilation. While these mechanisms are well characterized in arterioles, far less is known about how blood enters and is distributed within capillary networks, the site of oxygen and nutrient exchange. Because neuronal function requires rapid, on-demand perfusion, local mechanisms must regulate both capillary inflow and flow distribution. Capillary endothelial cells and pericytes, contractile cells that envelop capillaries, are emerging contributors to these processes, yet capillary-level autoregulation remains poorly defined.

Using an ex vivo pressurized retinal preparation that preserves the arteriole-to-capillary continuum, we examined how intraluminal viscosity, and thus shear stress, regulates endothelial and mural cell signaling during pressure-driven flow.

Increased viscosity delayed capillary filling and enhanced endothelial calcium activity in transitional and capillary segments. In contrast, viscosity suppressed pressure-induced calcium signaling in smooth muscle cells and ensheathing pericytes via nitric oxide-dependent inhibition. Chronic elevation of intraluminal viscosity induced arteriolar remodeling and increased tone but impaired endothelial shear sensing and reduced capillary perfusion.

These findings reveal fundamental differences in autoregulatory mechanisms between arterioles and capillaries and identify viscosity-driven endothelial signaling as a key determinant of capillary perfusion and flow distribution.