scholarly journals Rosiglitazone Restores Endothelial Dysfunction in a Rat Model of Metabolic Syndrome through PPARγ- and PPARδ-Dependent Phosphorylation of Akt and eNOS

PPAR Research ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Zhigang Zhao ◽  
Zhidan Luo ◽  
Peijian Wang ◽  
Jing Sun ◽  
Hao Yu ◽  
...  

Vascular endothelial dysfunction has been demonstrated in metabolic syndrome (MS). Chronic administration of rosiglitazone ameliorates endothelial dysfunction through PPARγ-mediated metabolic improvements. Recently, studies suggested that single dose of rosiglitazone also has direct vascular effects, but the mechanisms remain uncertain. Here we established a diet-induced rat model of MS. The impaired vasorelaxation in MS rats was improved by incubating arteries with rosiglitazone for one hour. Importantly, this effect was blocked by either inhibition of PPARγor PPARδ. In cultured endothelial cells, acute treatment with rosiglitazone increased the phosphorylation of Akt and eNOS and the production of NO. These effects were also abolished by inhibition of PPARγ, PPARδ, or PI3K. In conclusion, rosiglitazone improved endothelial function through both PPARγ- and PPARδ-mediated phosphorylation of Akt and eNOS, which might help to reconsider the complex effects and clinical applications of rosiglitazone.

2001 ◽  
Vol 281 (3) ◽  
pp. H981-H986 ◽  
Author(s):  
Zvonimir S. Katusic

Tetrahydrobiopterin is one of the most potent naturally occurring reducing agents and an essential cofactor required for enzymatic activity of nitric oxide synthase (NOS). The exact role of tetrahydrobiopterin in the control of NOS catalytic activity is not completely understood. Existing evidence suggests that it can act as alosteric and redox cofactors. Suboptimal concentration of tetrahydrobiopterin reduces formation of nitric oxide and favors “uncoupling” of NOS leading to NOS-mediated reduction of oxygen and formation of superoxide anions and hydrogen peroxide. Recent findings suggest that accelerated catabolism of tetrahydrobiopterin in arteries exposed to oxidative stress may contribute to pathogenesis of endothelial dysfunction present in arteries exposed to hypertension, hypercholesterolemia, diabetes, smoking, and ischemia-reperfusion. Beneficial effects of acute and chronic tetrahydrobiopterin supplementation on endothelial function have been reported in experimental animals and humans. Furthermore, it appears that beneficial effects of some antioxidants (e.g., vitamin C) on vascular function could be mediated via increased intracellular concentration of tetrahydrobiopterin. In this review, the potential role of tetrahydrobiopterin in the pathogenesis of vascular endothelial dysfunction and mechanisms underlying beneficial vascular effects of tetrahydrobiopterin will be discussed.


2007 ◽  
Vol 21 (5) ◽  
Author(s):  
Joëlle Magne ◽  
François Mariotti ◽  
Daniel Tome ◽  
Jean‐François Huneau

2013 ◽  
Vol 5 (6) ◽  
pp. 1663-1666 ◽  
Author(s):  
YING WEI ◽  
GELI LIU ◽  
JINGYAN YANG ◽  
RONGXIU ZHENG ◽  
LIHONG JIANG ◽  
...  

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