Targeting Phosphodiesterase-5 by Vardenafil Improves Vascular Graft Function

Area of Science:

• Vascular Surgery
• Cardiology
• Pharmacology

Background:

• Ischemia reperfusion (IR) injury is a significant complication during vascular graft harvesting and implantation.
• Elevated intracellular cyclic guanosine monophosphate (cGMP) levels are known to protect endothelial cells.
• The phosphodiesterase-5 inhibitor vardenafil may offer protection against IR injury by modulating the nitric oxide-cGMP pathway.

Purpose of the Study:

• To investigate the protective effects of vardenafil on vascular grafts against IR injury.
• To determine if vardenafil upregulates the nitric oxide-cGMP pathway in the vessel wall of bypass grafts.
• To assess the impact of vardenafil on endothelial function and cellular integrity post-reperfusion.

Main Methods:

• Lewis rats underwent aortic arch transplantation with or without vardenafil pre-treatment.
• Graft function was assessed by measuring endothelium-dependent and -independent vasorelaxations.
• Histological analyses included TUNEL staining, CD-31, ICAM-1, VCAM-1, α-SMA, nitrotyrosine, dihydroethidium, and cGMP immunochemistry.

Main Results:

• Vardenafil significantly improved maximal relaxation in reperfused grafts compared to saline controls.
• Vardenafil pre-treatment reduced DNA fragmentation, nitro-oxidative stress, and reactive oxygen species levels.
• Vardenafil preserved vascular smooth muscle cells, decreased ICAM-1 and VCAM-1 expression, and increased cGMP levels and endothelial integrity (CD-31).

Conclusions:

• Impaired intracellular cGMP signaling contributes to endothelial dysfunction in arterial grafts after bypass surgery.
• Vardenafil effectively prevents this dysfunction, supporting its role in preserving graft integrity.
• Clinical application of vardenafil as a preconditioning agent could represent a novel strategy in vascular and cardiac surgery.