Acute laminar shear stress reversibly increases human glomerular endothelial cell permeability via activation of endothelial nitric oxide synthase

作者：Bevan Heather S; Slater Sadie C; Clarke Hayley; Cahill Paul A; Mathieson Peter W; Welsh Gavin I; Satchell Simon C^*

来源：American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 2011, 301(4): F733-F742.

DOI：10.1152/ajprenal.00458.2010

• glomerulus
• transendothelial electrical resistance

Bevan HS, Slater SC, Clarke H, Cahill PA, Mathieson PW, Welsh GI, Satchell SC. Acute laminar shear stress reversibly increases human glomerular endothelial cell permeability via activation of endothelial nitric oxide synthase. Am J Physiol Renal Physiol 301: F733-F742, 2011. First published July 20, 2011; doi:10.1152/ajprenal.00458.2010.-Laminar shear stress is a key determinant of systemic vascular behavior, including through activation of endothelial nitric oxide synthase (eNOS), but little is known of its role in the glomerulus. We confirmed eNOS expression by glomerular endothelial cells (GEnC) in tissue sections and examined effects of acute exposure (up to 24 h) to physiologically relevant levels of laminar shear stress (10-20 dyn/cm(2)) in conditionally immortalized human GEnC. Laminar shear stress caused an orientation of GEnC and stress fibers parallel to the direction of flow and induced Akt and eNOS phosphorylation along with NO production. Inhibition of the phophatidylinositol (PI)3-kinase/Akt pathway attenuated laminar shear stress-induced eNOS phosphorylation and NO production. Laminar shear stress of 10 dyn/cm(2) had a dramatic effect on GEnC permeability, reversibly decreasing the electrical resistance across GEnC monolayers. Finally, the laminar shear stress-induced reduction in electrical resistance was attenuated by the NOS inhibitors L-N(G)-monomethyl arginine (L-NMMA) and L-N(G-)nitroarginine methyl ester (L-NAME) and also by inhibition of the PI3-kinase/Akt pathway. Hence we have shown for GEnC in vitro that acute permeability responses to laminar shear stress are dependent on NO, produced via activation of the PI3-kinase/Akt pathway and increased eNOS phosphorylation. These results suggest the importance of laminar shear stress and NO in regulating the contribution of GEnC to the permeability properties of the glomerular capillary wall.

• 出版日期2011-10