Retrograde shear stress modulates rat mesentery microvessel permeability and endothelial adhesion structures

Abstract

Vascular endothelial cells (EC) orient their long axis parallel to the fluid flow direction both in vivo and in culture. The EC surface glycocalyx transduces the fluid flow shear stress that mediates nitric oxide production (Florian et al. Circ Res 2003) and EC cytoskeletal rearrangement (Thi et al. PNAS 2004). To test that in vivo shear stress regulates EC adhesion structures and permeability we compared final hydraulic permeability (Lp) measured in rat mesentery venular microvessels perfused orthograde with Lp measured in vessels perfused retrograde, both for about 3 hours. Shear stress ranged from 0.2 to 17 dyne/cm2 in the retrograde group and from 3.2 to 36 in the orthograde group. For retrograde vessels Lp (range 0.4 to 30 x 10−7 (cm/s*cmH2O)) was significantly correlated (p < 0.05) to mean shear stress, with a linear regression slope 1.5 x 10−7 (cm/s*cmH2O)/(dyne/cm2) and Lp intercept ‐0.6 x 10−7 (cm/s*cmH2O). For orthograde vessels the Lp (2.0 ± 0.6 x 10−7 (cm/s*cmH2O)) was not correlated with mean shear stress. We also examined the continuity of the adhesion protein VE cadherin (VE) and that of the tight junction protein occludin (Oc). Significantly more discontinuities were observed for both VE and Oc in the retrograde group than in the orthograde group. In vivo reversal of flow direction stimulates increased Lp correlated with shear stress and induces rearrangement of cytoskeletal structures. HL44485