Nifedipine ameliorates ischemia-induced revascularization in diet-induced obese mice.
BACKGROUND
Obesity is a risk factor for the development of cardiovascular diseases that are associated with impaired angiogenesis. Nifedipine, a calcium-channel blocker, has a number of blood pressure (BP)-independent effects as well, such as improving endothelial function and decreasing oxidative stress. Here, we investigated whether nifedipine could improve the angiogenic responses in a diet-induced obese (DIO) model.


METHODS
DIO was induced by allowing 8-week-old C57BL/6J mice ad libitum access to a high-fat/high-sucrose (HF/HS) diet. Mice were randomly divided into two groups that were fed either the HF/HS or normal chow. At the age of 12 weeks, the animals were treated/not treated with nifedipine admixed with food at a concentration of 0.001%. Then, 1 week later, the mice were subjected to unilateral hind limb surgery.


RESULTS
Angiogenic repair of the ischemic hind limb was impaired in the DIO mice as compared with that in the control mice as evaluated by laser Doppler blood flowmetry (LDBF) and capillary density analysis. Treatment with nifedipine accelerated angiogenic repair in the DIO mice to a level equal to that seen in the control mice. DIO mice showed increased reactive oxygen species (ROS) production after hind limb ischemia. The number of endothelial progenitor cells (EPCs), which contribute to blood vessel formation, was also significantly lower in these mice. Nifedipine treatment ameliorated the oxidative status and increased the number of EPCs in the DIO mice.


CONCLUSIONS
Our observations demonstrated that DIO impaired revascularization in response to tissue ischemia. Nifedipine ameliorated obesity-impaired revascularization through suppressing oxidative stress and enhancing the number of EPCs.
Department of Cardiology, Nagoya University Graduate School of Medicine, Japan.
Tetsutaro
T
Kito
Rei
R
Shibata
Megumi
M
Kondo
Takashi
T
Yamamoto
Hirohiko
H
Suzuki
Masakazu
M
Ishii
Toyoaki
T
Murohara
D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002196:Capillaries / Q000503:physiopathology; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D042783:Endothelial Cells / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009543:Nifedipine / Q000627:therapeutic use*; D009765:Obesity / Q000150:complications*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species; D013234:Stem Cells / Q000187:drug effects
D002121:Calcium Channel Blockers; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D017382:Reactive Oxygen Species; D009543:Nifedipine