Comparative Relaxing Effects of Sildenafil, Vardenafil, and Tadalafil in Human Corpus Cavernosum: Contribution of Endogenous Nitric Oxide Release

ObjectivesTo 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.MethodsHCC 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 μmol/L).ResultsAll PDE-5 inhibitors tested (0.001-10 μmol/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 μmol/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 μmol/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 μmol/L each). All PDE-5 inhibitors significantly increased the duration of electrical field stimulation-induced relaxations (8 Hz).ConclusionsOur 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.