Objectives. In this study, we aimed to demonstrate the role of
sildenafil (an antagonist of
phosphodiesterase type 5 (PDE-5)) and
donepezil (a specific and reversible inhibitor of
acetylcholinesterase (Ach)) in increasing
ischemia-induced angiogenesis. Method.
Critical limb ischemia was induced by
ligation of the common femoral artery followed by
ligation of the common iliac artery. The operated animals were divided into 3 groups: receiving
sildenafil, receiving
donepezil, and surgery alone; the contralateral lower limb was used as a negative control. The results were controlled based on clinical score and Doppler ultrasound. Gastrocnemius muscle samples were taken from all animals, both from the ischemic and nonischemic limb and were used for histopathological and immunohistochemical examination for the evaluation of the number of nuclei/field, endothelial cells (CD31), dividing cells (Ki-67), and
vascular endothelial growth factor (VEGFR-3). Results. An increasing tendency of the number of nuclei/field with time was observed both in the case of
sildenafil and
donepezil treatment. The formation of new capillaries (the angiogenesis process) was more strongly influenced by
donepezil treatment compared to
sildenafil or no treatment. This treatment significantly influenced the capillary/fiber ratio, which was increased compared to untreated ligated animals.
Sildenafil treatment led to a gradual increase in the number of dividing cells, which was significantly compared to the negative control group and compared to the
ligation control group. The same effect (increase in the number of Ki-67 positive cells) was more obvious in the case of
donepezil treatment. Conclusion.
Donepezil treatment has a better effect in
ligation-induced
ischemia compared to
sildenafil, promoting angiogenesis in the first place, and also arteriogenesis.