vardenafil-dihydrochloride and 3-nitrotyrosine

Ischaemia reperfusion (IR) injury occurs during vascular graft harvesting and implantation during vascular/cardiac surgery. Elevated intracellular cyclic guanosine monophosphate (cGMP) levels contribute to an effective endothelial protection in different pathophysiological conditions. The hypothesis that the phosphodiesterase-5 inhibitor vardenafil would protect vascular grafts against IR injury by upregulating the nitric oxide-cGMP pathway in the vessel wall of the bypass graft was investigated.. Lewis rats (n = 6-7/group) were divided into Group 1, control; Group 2, donor rats received intravenous saline; Group 3, received intravenous vardenafil (30 μg/kg) 2 h before explantation. Whereas aortic arches of Group 1 were immediately mounted in an organ bath, aortic segments of Groups 2 and 3 were stored for 2 h in saline and transplanted into the abdominal aorta of the recipient. Two hours after transplantation, the implanted grafts were harvested. Endothelium dependent and independent vasorelaxations were investigated. TUNEL, CD-31, ICAM-1, VCAM-1, α-SMA, nitrotyrosine, dihydroethidium and cGMP immunochemistry were also performed.. The results support the view that impairment of intracellular cGMP signalling plays a role in the pathogenesis of the endothelial dysfunction of an arterial graft after bypass surgery, which can effectively be prevented by vardenafil. Its clinical use as preconditioning drug could be a novel approach in vascular/cardiac surgery.

Topics: Actins; Animals; Aorta, Thoracic; Cold Ischemia; Cyclic GMP; Cytoprotection; DNA Damage; Intercellular Adhesion Molecule-1; Male; Nitrosative Stress; Phosphodiesterase 5 Inhibitors; Platelet Endothelial Cell Adhesion Molecule-1; Rats, Inbred Lew; Reperfusion Injury; Signal Transduction; Tissue and Organ Harvesting; Tyrosine; Vardenafil Dihydrochloride; Vascular Cell Adhesion Molecule-1; Vascular System Injuries; Vasodilator Agents; Warm Ischemia