Abstract
IntroductionPDE5 inhibitors (PDE5inhs) have proven to be of great impact in the treatment of numerous human extra-sexual diseases and their chronic use may induce endothelial rehabilitation. This study aimed to assess the effects of PDE5inhs at chronic administration to explore the possible endothelial cyto-protective and thrombo-resistance effects.Material and methodsOne hundred New Zealand white male rabbits were divided into four groups. The first group (control, C) received 1 ml saline/kg, the second group (S) received 10 mg/kg sildenafil, the third group (V) received 2 mg/kg vardenafil, and the fourth group (T) received 2 mg/kg tadalafil in saline I.P. three times weekly for 4 weeks. Blood samples were collected and plasma was isolated for determination of 2,3-dinor-6-keto-prostaglandin F-1α (PGF1α), 11-dehydro-TXB2 (TXB2), fibrinogen, calcium levels, prothrombin (PT), and thrombin times (TT).ResultsPDE5inhs significantly increase PGF1α, calcium levels, PT and TT (p < 0.001) when compared with baseline data or with the saline group at the end of treatment. In contrast, PDE5inhs significantly decrease TXB2 and fibrinogen levels (p < 0.001) when compared either with their baseline data or with the saline group at the end of treatment. The tadalafil group showed a lower increase in PGF1α (p < 0.001), lower decrease in TXB2 (p < 0.001), and higher increase in calcium levels (p < 0.01, p < 0.05), lower increase in PT and TT levels (p < 0.001) when compared with sildenafil or vardenafil.ConclusionsThe prolonged use of PDE5inhs has time-dependent mild to moderate endothelial cyto-protective, thrombo-resistance anti-inflammatory and anti-nociception effects via activation of endothelial NOS (eNOS), increase of PGI2 synthesis and decrease of fibrinogen with significant increase in PT and TT.
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