title: Effect of avanafil on rat and human corpus cavernosum.
abstract: We compared the activity of a new phosphodiesterase-5 inhibitor (PDE5i) avanafil with sildenafil and tadalafil in human and rat corpus cavernosum (CC) tissues. The effect of avanafil with several inhibitors and electrical field stimulation (EFS) was evaluated on CC after pre-contraction with phenylephrine. With the PDE5i, sildenafil and tadalafil, concentration-response curves were obtained and cyclic guanosine monophosphate (cGMP) levels were measured in tissues. Avanafil induced relaxation with maximum response of 74 ± 5% in human CC. This response was attenuated by NOS inhibitor and soluble guanylate cyclase (sGC) inhibitor. Avanafil potentiated relaxation responses to acetylcholine and EFS in human CC and enhanced SNP-induced relaxation and showed 3-fold increase in cGMP levels. When compared with sildenafil, avanafil and tadalafil were effective at lower concentrations in human CC. In addition, Sprague-Dawley rats underwent in vivo intracavernosal pressure (ICP) and mean arterial pressure (MAP) measurements. Avanafil increased ICP/MAP that was enhanced by SNP and cavernous nerve (CN) stimulation in rat CC tissues. Also avanafil showed maximum relaxation response of 83 ± 7% in rat CC with 3-fold increase in cGMP concentration. Taken together, these results of our in vivo and in vitro studies in human and rat suggest that avanafil promotes the CC relaxation and penile erection via NO-cGMP pathway.
authors.affiliation: Department of Urology, Tulane University Health Sciences Center, New Orleans, LA, USA.|Department of Pharmacology, School of Pharmacy, Ankara University, Ankara, Turkey.
authors.forename: S
authors.initials: S
authors.lastname: Gur
authors.affiliation: Department of Urology, Tulane University Health Sciences Center, New Orleans, LA, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Sikka
authors.affiliation: Department of Pharmacology, Tulane University Health Sciences Center, New Orleans, LA, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Pankey
authors.affiliation: Department of Pharmacology, Tulane University Health Sciences Center, New Orleans, LA, USA.
authors.forename: G F
authors.initials: GF
authors.lastname: Lasker
authors.affiliation: Department of Urology, Tulane University Health Sciences Center, New Orleans, LA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Chandra
authors.affiliation: Department of Pharmacology, Tulane University Health Sciences Center, New Orleans, LA, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Kadowitz
authors.affiliation: Department of Urology, Tulane University Health Sciences Center, New Orleans, LA, USA.
authors.forename: W J G
authors.initials: WJ
authors.lastname: Hellstrom
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D010413:Penis / Q000098:blood supply / Q000737:chemistry / Q000187:drug effects*; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate / Q000494:pharmacology; D000068581:Tadalafil / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D011743:Pyrimidines; D000068581:Tadalafil; D000068677:Sildenafil Citrate; C553414:avanafil; D006152:Cyclic GMP
keywords: Avanafil; cGMP-electrical field stimulation; human and rat corpus cavernosum; nitric oxide; relaxation