title: Metformin enhances nitric oxide production and diminishes Rho kinase activity in rats with hyperlipidemia.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Congwu
authors.initials: C
authors.lastname: Huang
authors.forename: Chuan
authors.initials: C
authors.lastname: Ceng
authors.forename: Haiyong
authors.initials: H
authors.lastname: Zhan
authors.affiliation: The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China. Zhengyunsen@126.com.
authors.forename: Dongdan
authors.initials: D
authors.lastname: Zheng
authors.forename: Weixing
authors.initials: W
authors.lastname: Han
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000069059:Atorvastatin; D002097:C-Reactive Protein / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000097:blood; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D054460:rho-Associated Kinases / Q000097:blood*
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D009569:Nitric Oxide; D002097:C-Reactive Protein; D008687:Metformin; D000069059:Atorvastatin; D054460:rho-Associated Kinases