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

Liu Y, Huang C, Ceng C, Zhan H, Zheng D, Han W - Lipids Health Dis (2014)

Bottom Line: Whether cardio-protective effect of metformin is associated with Rho kinase activity is unknown.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China. Zhengyunsen@126.com.

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.

Conclusion: 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.

Show MeSH

Related in: MedlinePlus

Denote: *P < 0.05 versus other groups at 6 weeks of hyperlipidemia model production, #P < 0.05 versus atorvastatin, metformin and combined groups, &P < 0.05 versus atorvastatin and metformin groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4109376&req=5

Figure 1: Denote: *P < 0.05 versus other groups at 6 weeks of hyperlipidemia model production, #P < 0.05 versus atorvastatin, metformin and combined groups, &P < 0.05 versus atorvastatin and metformin groups.

Mentions: As shown in Figures 1 and2, 6 weeks of high-fat and high-cholesterol diet administration, NO production was profoundly declined in the hyperlipidemia groups in comparison to the sham group (P < 0.05). In contrast, Rho kinase activity was elevated in all hyperlipidemia groups (P < 0.05 versus sham group). With 4 weeks of metformin and atorvastatin therapy, NO production was increased in accompany with Rho kinase activity decrease in the atorvastatin and metformin groups, and these efficacies were further enhanced with combined therapy (P < 0.05 versus atorvastatin and metformin groups). Notably, with 4 weeks of medical intervention, the magnitude of Rho kinase activity decrease appeared to be more significant in the combined groups (132.8 ± 15.5 U/L) than that of the metformin (145.2 ± 16.7 U/L) and atorvastatin group (141.6 ± 13.7 U/L) but without statistical significance.


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

Liu Y, Huang C, Ceng C, Zhan H, Zheng D, Han W - Lipids Health Dis (2014)

Denote: *P < 0.05 versus other groups at 6 weeks of hyperlipidemia model production, #P < 0.05 versus atorvastatin, metformin and combined groups, &P < 0.05 versus atorvastatin and metformin groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4109376&req=5

Figure 1: Denote: *P < 0.05 versus other groups at 6 weeks of hyperlipidemia model production, #P < 0.05 versus atorvastatin, metformin and combined groups, &P < 0.05 versus atorvastatin and metformin groups.
Mentions: As shown in Figures 1 and2, 6 weeks of high-fat and high-cholesterol diet administration, NO production was profoundly declined in the hyperlipidemia groups in comparison to the sham group (P < 0.05). In contrast, Rho kinase activity was elevated in all hyperlipidemia groups (P < 0.05 versus sham group). With 4 weeks of metformin and atorvastatin therapy, NO production was increased in accompany with Rho kinase activity decrease in the atorvastatin and metformin groups, and these efficacies were further enhanced with combined therapy (P < 0.05 versus atorvastatin and metformin groups). Notably, with 4 weeks of medical intervention, the magnitude of Rho kinase activity decrease appeared to be more significant in the combined groups (132.8 ± 15.5 U/L) than that of the metformin (145.2 ± 16.7 U/L) and atorvastatin group (141.6 ± 13.7 U/L) but without statistical significance.

Bottom Line: Whether cardio-protective effect of metformin is associated with Rho kinase activity is unknown.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China. Zhengyunsen@126.com.

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus