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Chronic Sildenafil Improves Erectile Functionand Endothelium-dependent Cavernosal Relaxations in Rats: Lack of Tachyphylaxis

Behr-Roussela D, Gornya D, Mevela K, Caiseya S, Bernabe´a J, Burgessb G, Waymanb C, Alexandrea L, Francois Giulianoac F; European Urology 47 (2005) 87-91

KEY WORDS: Erectile dysfunction; Sildenafil; PDE-5; Tachyphylaxis; Chronic administration; Corpus cavernosum; Endothelium

Penile erection, occurring in response to the activation of pro-erectile autonomic pathways, is greatly dependent on adequate inflow of blood to the erectile tissue and requires coordinated arterial endothelium-dependent vasodilatation and sinusoidal endothelium-dependent cavernosal smooth muscle relaxation. Sildenafil was the first orally active drug to treat patients with erectile dysfunction (ED) and has become the standard treatment for ED in more than 110 countries. Chronic treatment with sildenafil could help patients with ED.

• The effects of an 8-week long treatment with sildenafil (60 mg/kg/d sc) in male Sprague Dawley rats were evaluated on electrically-elicited erectile responses in vivo before and after an acute injection of sildenafil (0.3 mg/ kg iv). In addition, endothelium-dependent and -independent relaxations of strips of corpus cavernosum in vitro were examined.
• Endothelium-dependent relaxations of cavernosal strips to acetylcholine were enhanced after chronic treatment with sildenafil while relaxations to A23187 or sodium nitroprusside were unchanged. Frequency dependent erectile responses elicited by cavernous nerve stimulation were significantly improved. Moreover, the erectile responses to acute sildenafil were greater in chronically-treated rats with sildenafil.
• This is the first report providing experimental support for chronic dosing with sildenafil which could be of use for patients that are poor responders to on-demand treatment. Chronic sildenafil may regulate the transduction pathway leading to the activation of eNOS but has no effect on NO bioavailability or on the cGMP pathway, thereby eliminating a possible concern for tachyphylaxis.

See the abstract

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15582254&dopt=Citation