Basic and Translational ScienceComparative Relaxing Effects of Sildenafil, Vardenafil, and Tadalafil in Human Corpus Cavernosum: Contribution of Endogenous Nitric Oxide Release
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Material and Methods
HCC tissue from 16 individuals (14-65 years old) obtained from patients who had undergone penile prosthesis implantation or multiple organ donation was used after informed consent was obtained from the appropriate person. The University Hospital Ethics Committee approved the protocol.
Relaxant Response Elicited by PDE-5 Inhibitors in HCC
PE (10 μmol/L) caused submaximal HCC contractions of 56.4 ± 8.2 mN (n = 78). Figure 1 shows that the cumulative addition of sildenafil, vardenafil, and tadalafil (0.001-10 μmol/L; n = 4 each) to the bathing medium produced long-lasting and concentration-dependent relaxations in PE-precontracted tissues, with a negative logarithm of the median effective concentration (pEC50) value of 6.67 ± 0.14, 6.71 ± 0.11, and 6.78 ± 0.12 for sildenafil, vardenafil, and tadalafil, respectively. The maximal
Comment
The results of the present study have shown that sildenafil, vardenafil, and tadalafil relax HCC strips in a concentration-dependent manner, but the maximal relaxing response for tadalafil was significantly lower than that with the 2 other PDE-5 inhibitors. In addition, all PDE-5 inhibitors potentiated both endogenous and exogenous NO-mediated HCC relaxation.
The PDE-5 isoform is abundantly expressed in the corpora cavernosal of the penis, where it is thought to be responsible for penile
Conclusions
Our results have shown that sildenafil, vardenafil, and tadalafil potently relax HCC tissues in vitro, and interact with endogenous and exogenous NO, amplifying their relaxing effects. The maximal HCC relaxation obtained with tadalafil was significantly lower than those obtained with sildenafil and vardenafil. However, considering that vardenafil presents with a lower bioavailability and larger volume of distribution compared with tadalafil, our data suggest that the functional differences
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