Shear Stress Generated by Different Fluid Compositions Induces Differential Endothelial Signaling in Intact Venules

Abstract

Disturbed shear stress promotes atherosclerosis, thrombosis, and inflammation of the vessel wall. Most shear stress studies have been conducted in large arterial segments or cultured endothelial cells (ECs). Shear stress induced EC signaling and its role in the regulation of microvessel function have not been well explored in intact venules. The objective of this study was to investigate the EC [Ca2+]i and nitric oxide (NO) responses at the onset of shear stress generated by different fluids. Shear stress was quantified by measuring the flow velocity and fluid viscosity using a high speed camera and cone‐plate viscometer. The changes of EC [Ca2+]i and NO were measured in Fura‐2 AM and DAF‐2 DA loaded individually perfused rat mesenteric venules. Transient increases in EC [Ca2+]i occurred only with whole blood perfusion. The peak EC [Ca2+]i of 203 ± 17 and 288 ± 18 nM were observed with shear stress at 11 and 32 dyn/cm2(n=5), respectively. Shear stress generated by the perfusion of albumin–Ringer, plasma, and Dextran 70‐albumin‐Ringer solution caused no changes in EC [Ca2+]i. However, both plasma and whole blood perfusion induced shear magnitude‐dependent NO production. These results indicated that in intact venules shear stress‐induced increases in EC [Ca2+]i require the presences of erythrocytes, while shear stress‐induced NO production can be independent of Ca2+ signaling. Supported by HL56237 and HL084338.