Protective Effect Of Omapatrilat On Human Umbilical Vein Endothelial Cell Injury Induced By Angiotensin Ⅱ In Culture

Objectives: To investigate the protective effect and mechanisms of action of Omapatrilat on human umbilical vein endothelial cells (HUVECs) injury and apoptosis induced by angiotensin II(Ang II) in culture.Methods: HUVECs were divided into 4 groups: control (n=4), AngⅡ (n=4), omapatrilat (n=4), and AngⅡ+omapatrilat (n=4). Flow cytometry (FCM) was used to evaluate cell cycle and apoptosis; Nitric oxide (NO) levels were measured by colorimetry; dysfunction of HUVECs was determined by measuring lactate dehydrogenase (LDH) leakage, endothelin-1 (ET-1) release and expression of intercellular adhesion molecule-1 (ICAM-1) in HUVECs membranes by spectrophotometry, radioimmunoassay, immunohistochemistry and image analysis.Results: (1)Exposure of HUVECs to Ang II (10~-7 mol L~-1) for 24h significantly increased HUVECs LDH leakage and ET-1 release (217.52±61.65 vs. 82.28 ±22.83 ,P < 0.01; 86.15±15.82 vs. 51.63±8.65 control,P < 0.01,respectively).ICAM-l expression (P < 0.01) and apoptosis percentage(P < 0.01) were also significantly increased, while NO production(P < 0.05) and HUVECs proliferation both decreased.(2)Omapatrilat(10~-6 mol L~-1) caused a significant decrease in LDH leakage and ET-1 release (131.75±31.46 vs. 217.52±61.65 P < 0.05; 63.15±7.35 vs. 86.15±15.82 for the Angll group, P < 0.05, respectively), ICAM-1 expression (P < 0.01) and apoptosis percentage (P < 0.01) both decreased, while HUVECs NO production (P<0.05 ) and cell proliferation both increased.Conclusions: Ang II can injury HUVECs and induce their apoptosis as well as inhibit NO synthesis and cell proliferation. Omapatrilat can significantly protect dysfunction in HUVECs exposed to Ang II in vitro, increase HUVECs NO production and promote cell proliferation .