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Metformin enhances nitric oxide production and diminishes Rho kinase activity in rats with hyperlipidemia

Yan Liu14, Congwu Huang2, Chuan Ceng2, Haiyong Zhan2, Dongdan Zheng3* and Weixing Han1*

Author Affiliations

1 The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China

2 The Department of Internal Medicine, the Second Affiliated Hospital of Shantou University, Shantou, Guangdong Province, China

3 The Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China

4 The Third people's hospital of Huizhou, Huizhou, Guangdong Province, China

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Lipids in Health and Disease 2014, 13:115  doi:10.1186/1476-511X-13-115

Published: 15 July 2014



Rho kinase over-activation is associated with nitric oxide (NO) reduction and atherosclerosis. Metformin is favorable for endothelial function improvement and cardiovascular outcomes. Whether cardio-protective effect of metformin is associated with Rho kinase activity is unknown.


Hyperlipidemia model of rats were established accordingly. Thereafter, medical interventions in terms of atorvastatin, metformin or combined therapy were administered for 4 weeks. Laboratory parameters were compared among each groups at initial, 6 weeks of high-fat and high-cholesterol diet administration, and 4 weeks of medical intervention. Lineal regression analyses were performed.


No significant difference of laboratory parameters was observed initially. Six weeks of high-fat and high-cholesterol diet administration, serum levels of cholesterol, C-reactive protein (CRP) level, and Rho kinase activity were significantly increased while NO production was concomitantly reduced in comparison to the sham group. After 4 weeks of medical intervention, CRP level and Rho kinase activity were profoundly diminished while NO production was significantly enhanced in the atorvastatin and metformin groups, and these benefits were further enhanced with combined therapy. Lineal regression analyses showed that Rho kinase activity was negatively correlated with NO production but positively correlated with CRP level.


In rats with hyperlipidemia, metformin and atorvastatin therapy is favorable for NO production and CRP reduction, which might be associated with Rho kinase activity decrease.

Hyperlipidemia; Nitric oxide; Rho kinase