Details

Autor(en) / Beteiligte

• García-Prieto, C.F
• Pulido-Olmo, H
• Ruiz-Hurtado, G
• Gil-Ortega, M
• Aranguez, I
• Rubio, M.A
• Ruiz-Gayo, M
• Somoza, B
• Fernández-Alfonso, M.S

Titel

Mild caloric restriction reduces blood pressure and activates endothelial AMPK-PI3K-Akt-eNOS pathway in obese Zucker rats

Ist Teil von

• Vascular pharmacology, 2015-02, Vol.65, p.3-12

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• Abstract Genetic obesity models exhibit endothelial dysfunction associated to adenosine monophosphate-activated protein kinase (AMPK) dysregulation. This study aims to assess if mild short-term caloric restriction (CR) restores endothelial AMPK activity leading to an improvement in endothelial function. Twelve-week old Zucker lean and obese ( fa/fa ) male rats had access to standard chow either ad libitum (AL, n = 8) or 80% of AL (CR, n = 8) for two weeks. Systolic blood pressure was significantly higher in fa/fa AL rats versus lean AL animals, but was normalized by CR. Endothelium-dependent relaxation to acetylcholine (ACh, 10 − 9 to 10 − 4 M) was reduced in fa/fa AL compared to control lean AL rats (p < 0.001), and restored by CR. The AMPK activator AICAR (10 − 5 to 8·10 − 3 M) elicited a lower relaxation in fa/fa AL rings that was normalized by CR (p < 0.001). Inhibition of PI3K (wortmannin, 10 − 7 M), Akt (triciribine, 10 − 5 M), or eNOS (L-NAME, 10 − 4 M) markedly reduced AICAR-induced relaxation in lean AL, but not in fa/fa AL rats. These inhibitions were restored by CR in Zucker fa/fa rings. These data show that mild short-term CR improves endothelial function and lowers blood pressure in obesity due to the activation of the AMPK–PI3K–Akt–eNOS pathway.