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  • Title: Comparative relaxing effects of sildenafil, vardenafil, and tadalafil in human corpus cavernosum: contribution of endogenous nitric oxide release.
    Author: Toque HA, Priviero FB, Teixeira CE, Claudino MA, Baracat JS, Fregonesi A, De Nucci G, Antunes E.
    Journal: Urology; 2009 Jul; 74(1):216-21. PubMed ID: 19371941.
    Abstract:
    OBJECTIVES: To compare the direct relaxant activity of sildenafil, vardenafil, and tadalafil in the human corpus cavernosum (HCC) and to investigate their modulatory effects on nitric oxide (NO)-mediated responses. Phosphodiesterase (PDE)-5 inhibitors cause cavernosal smooth muscle relaxation and penile erection. METHODS: HCC strips were mounted in 10-mL organ baths containing Krebs solution and connected to force-displacement transducers. The changes in isometric force were recorded using the Powerlab 400 data acquisition system. Corporeal smooth muscle was precontracted submaximally with phenylephrine (10 micromol/L). RESULTS: All PDE-5 inhibitors tested (0.001-10 micromol/L) relaxed phenylephrine-precontracted HCC with similar values of potency in a concentration-dependent manner. However, the maximal relaxations induced by tadalafil (83% +/- 4%) were significantly lower compared with sildenafil (107% +/- 5%) and vardenafil (111% +/- 3%). The NO synthesis inhibitor N-nitro-l-arginine methyl ester (100 micromol/L) caused significant rightward shifts in the concentration-response curves for sildenafil (4.0-fold), vardenafil (4.6-fold), and tadalafil (3.2-fold) in HCC tissue. The guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 micromol/L) also produced similar rightward shifts for these PDE-5 inhibitors. The cavernosal relaxations evoked by either acetylcholine or the NO donor glyceryl trinitrate were markedly potentiated by sildenafil, vardenafil, and tadalafil (0.1 micromol/L each). All PDE-5 inhibitors significantly increased the duration of electrical field stimulation-induced relaxations (8 Hz). CONCLUSIONS: Our findings have shown that sildenafil, vardenafil, and tadalafil relax HCC tissues in a concentration-dependent manner, but the maximal relaxation obtained with tadalafil was significantly lower than that obtained with sildenafil and vardenafil. Moreover, the PDE-5 inhibitors interacted with endogenous and exogenous NO, amplifying its HCC relaxation.
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