Role of Rho kinase in diabetic vascular endothelial dysfunction |
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Authors: | WU Jian-mei CHEN Xiao-na GUO Zheng-xiang JI Xiao-wei SHI Qiao-ya YIN Hong-ping SHEN Li RU Hai-long LIN Guo-hua LIU Chuan-fei LIU Cui-qing |
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Institution: | Department of Physiology, Department of Basic Medicine, Hangzhou Normal University, Hangzhou 310036, China |
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Abstract: | AIM: To investigate the role of Rho kinase in diabetic vascular endothelial dysfunction. METHODS: SD rats, genetic db/db diabetic model and high-fat diet-induced obese mice were used in this study. The thoracic aorta of the rats or mice were isolated and suspended in organ bath or myograph for measurement of the changes in isometric tensions. The levels of phosphorylated endothelial nitric oxide synthase(eNOS) were determined by Western blotting. Thromboxane B2(TXB2),prostaglandin F2α(PGF2α) and thromboxane receptor (TP receptor) activators in artery were measured by ELISA. RESULTS: Endothelium-dependent vasorelaxation was attenuated by TP receptor activation, which was ameliorated by Rho kinase inhibitors. The improved endothelium-dependent vasorelaxation by inhibition of Rho kinase was abolished by pretreatment with the inhibitor of eNOS. Consistently, the level of phosphorylated eNOS was inhibited by TP receptor activation, which was reversed by inhibition of Rho kinase. The endothelium-dependent vasorelaxation was also improved by Rho kinase inhibitors in diabetic and obese animals. The levels of TXB2 and PGF2α in the arteries were increased in diabetic animals compared with the controls. CONCLUSION: Rho kinase plays a role in diabetic endothelial dysfunction, which may be related to TP receptor activation and eNOS inhibition. |
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Keywords: | Rho kinase Receptors thromboxane Endothelium vascular Diabetes mellitus |
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