Mechanism of endothelial cyto-protective and thrombo-resistance effects of sildenafil, vardenafil and tadalafil in male rabbit

西地那非、伐地那非和他达拉非对雄兔内皮细胞保护及抗血栓作用的机制

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作者:Mohamed-I Kotb El-Sayed, Hatem Al-Kordy A Amin

Conclusions

The 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.

Material and methods

One 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).

Methods

One 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).

Results

PDE5inhs 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. Conclusions: The 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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