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Effect of Chronic Tadalafil Administration on Penile Hypoxia Induced by Cavernous Neurotomy in the Rat
Abstract
Background: Numerous men develop postprostatectomy erectile dysfunction (PPED), due to surgery-related nervous damage. PPED is often refractory to phosphodiesterase type 5 (PDE5) inhibitors therapy. Aim: To verify whether chronic tadalafil (CT) preserves bilateral cavernous neurotomy (BCN)-induced penile damage and hypo-oxygenation. Methods: In a rat model of BCN we evaluated in vitro and ex vivo effect of CT treatment (2 mg/kg, daily for 3 months). Results: Bilateral cavernous neurotomy induced massive hypoxia and decreased muscle/fiber ratio, completely restored by CT. Hypersensitivity of hypoxic tissues to the relaxant effect of the endothelin type B receptor (ETB) agonist IRL-1620 was observed, along with ETB mRNA and protein overexpression. CT restored sensitivity to IRL-1620, and normalized ETB expression. Hypoxic penis showed increased sensitivity to the relaxant effect of the nitric oxide donor sodium nitroprusside (SNP), while acute tadalafil (100 nM) did not amplify the SNP effect. Accordingly, PDE5 mRNA and protein were reduced in BCN penile tissues. By restoring PDE5, CT decreased SNP-induced relaxation and rescued sensitivity to acute tadalafil. However, in hypoxic penis, CT normalizes neither acetylcholine hyporesponsiveness nor neuronal nitric oxide synthase-endothelial nitric oxide synthase expression. Conclusion: Chronic tadalafil restores some of the investigated BCN-induced alterations, including PDE5 and tadalafil efficacy.
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“Similarly, Vignozzi et al also found that once-daily tadalafil given to rats that have undergone bilateral cavernosal nerve resection reversed the decline in cavernosal smooth muscle to collagen ratio (Vignozzi et al 2006).”
From Tadalafil in the treatment of erectile dysfunction (2008) · cites this paper as Vignozzi et al 2006
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Cited by
Guidelines on male sexual dysfunction: erectile dysfunction and premature ejaculation
Hatzimouratidis, K., Amar, E., Eardley, I., Giuliano, F., Hatzichristou, D., Montorsi, F., Vardi, Y., & Wespes, E. (2010) · European Urology · doi:10.1016/j.eururo.2010.02.020 · Cited by 1,223
Tadalafil in the treatment of erectile dysfunction
Coward, R., & Carson, C. (2008) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s3336 · Cited by 138
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Penile rehabilitation after radical prostatectomy: does it work?
(2015) · PubMed Central · doi:10.3978/j.issn.2223-4683.2015.02.01 · Cited by 40
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Metadata
- Authors
- Vignozzi, L., Filippi, S., Morelli, A., Ambrosini, S., Luconi, M., Vannelli, G. B., Donati, S., Crescioli, C., Zhang, X.-H., Mirone, V., Forti, G., & Maggi, M.
- Affiliations
- Andrology Unit Department of Clinical Physiopathology Center of Research Transfer and High Education , Florence , Italy
- Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction Departments of Pharmacology and Clinical Physiopathology , Florence , Italy
- Department of Anatomy Histology and Forensic Medicine University of Florence , Florence , Italy
- Department of Urology University of Medicine , Naples , Italy
- Venue
- The Journal of Sexual Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-05-01
- Volume
- 3
- Issue
- 3
- Pages
- 419-431
- ISSN
- 1743-6109
- 1743-6095
- Cited by
- 108
- References
- 1
- Language
- en
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- Vignozzi, L., Filippi, S., Morelli, A., Ambrosini, S., Luconi, M., Vannelli, G. B., Donati, S., Crescioli, C., Zhang, X.-H., Mirone, V., Forti, G., & Maggi, M. (2006). Effect of Chronic Tadalafil Administration on Penile Hypoxia Induced by Cavernous Neurotomy in the Rat. The Journal of Sexual Medicine. https://doi.org/10.1111/j.1743-6109.2006.00208.x
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