Fluid Shear Stress Regulated The Expression Of Endothelial Nitric Oxide Synthase In Pulmonary Arterial Endothelial Cells

BACKGROUND: Nitric oxide is a vasoactive substance secreted by endothelial cells,There are two functions:(1) dilate blood vessels and (2) inhibit the proliferation ofvascular smooth muscle cells. L-arginine synthesize NO catalyzed by the endothelialnitric oxide synthase, ie eNOS, so the expression of eNOS in the level directlydetermines the quantity of NO. Significant increasment of pulmonary blood flow isthe main pathophysiological change of letf-right shunt congenital heart diseaseBecause vascular endothelial cells attached to the inner wall of the vessel lumen, highpulmonary blood flow can lead to high shear force, causing pulmonary arterialendothelial cells (PAECs) morphological and functional changes. Whether NO playan important role in pulmonary vascular remodeling is currently no consistency ofopinions, and the majority of experimental studies or animal experiments imposedchronic injury factors or surgical biopsy of patients with advanced stage or anautopsy case studies most of them limited to chronic or late molecular pathologicalevents. The functional changes of NO and eNOS in the early stage of the diseaserarely has been reported.Objective： To investigate the effect of fluid shear stress on PAECs, the studyprovides an understanding of the early pathophysiology changes of pulmonaryhypertension.Methods： PAECs were exposed to different level fluid shear stress in flow chamber and divid22ed into sationary group (0dyn/cm)，low-flow shear stress group (1dyn/cm)and high-flow shear stress group (3dyn/cm)，RT-PCR was used to estimate the eNOSmRNA expression of PAECs, and Western blot was carried out to examine the eNOSprotein expression of PAECs in different groups.Results： eNOS mRNA and protein expression of PAECs increased varying with thestress load.Conclusion： Fluid shear stress can upregulated eNOS mRNA and protein expressionof PMVECs varying with the stress load, which indicated that increased eNOs mayhas an compensative action on early stage of pulmonary hypertension.