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Current Vascular Pharmacology


ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

Research Article

Beneficial Effects of Sildenafil on Tissue Perfusion and Inflammation in a Murine Model of Limb Ischemia and Atherosclerosis

Author(s): Aggeliki Valatsou, Alexandros Briasoulis, Georgia Vogiatzi, Alsistis Pantopoulou, Evangelos Oikonomou*, Antigoni Miliou, Despina Perrea and Dimitris Tousoulis

Volume 15 , Issue 3 , 2017

Page: [282 - 287] Pages: 6

DOI: 10.2174/1570161115666170126123258

Price: $65


Background: Sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, has endothelium protective and angiogenic effects.

Objectives: To test if sildenafil improves tissue perfusion and neovascularization and downregulates proinflammatory molecules following limb ischemia.

Methods: 30 ApoE-/- male mice, bred with cholesterol rich diet for 4 weeks, were anesthetized and underwent unilateral hind-limb ischemia with ligation of the left femoral artery. Mice were randomized in 2 groups: sildenafil (1 mg/Kg for 7 days intraperitoneally, i.p.) or normal saline (0.4 ml for 7 days, i.p.). Bilateral hind-limb perfusion was estimated by laser Doppler imaging after surgery on days 0, 7 and 28.

Results: Sildenafil significantly reduced at day 28 compared with day 0 levels of soluble intracellular adhesion molecule-1(sICAM-1) [2.24(1.81-2.41) vs. 1.29(0.87-1.45) ng/ml, p=0,01], soluble E-selectin (sE-Selectin) [5.52 (3.67-6.14) vs 1.71 (1.42-2.86) ng/ml, p=0.02] and tissue plasminogen activator inhibitor- 1 (tPAI-1) [0.13(0.07-0.21) vs 0.08 (0.04-0.10) ng/ml, p=0.01] while normal saline had no effect on the levels of sICAM-1, sE-Selectin and tPAI-1. Treatment with sildenafil was associated with increased perfusion in the ischemic limb compared with controls.

Conclusion: Sildenafil exerts significant beneficial effects on tissue perfusion and inflammatory status after limb ischemia, a finding implying neovascularization and potential vascular protective properties of sildenafil.

Keywords: Sildenafil, ischemia, neovascularization, pro-inflammatory molecules, laser doppler.

Graphical Abstract

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