title: Effect of a single treatment with tadalafil on blood flow in lower urinary tract tissues in rat models of bladder overdistension/emptying and abdominal aorta clamping/release.
abstract: Impaired blood flow in lower urinary tract (LUT) tissues is a pathophysiological cause of LUT symptoms. We investigated the effects of the phosphodiesterase 5 (PDE5) inhibitor tadalafil on the sustained decrease in bladder blood flow (BBF) and time-dependent changes in BBF and prostate blood flow (PBF) resulting from ischemia/reperfusion in two rat models. In a rat model of bladder overdistension/emptying (O/E), the bladder was overdistended by saline infusion and emptied after 2h. Tadalafil was administered intraduodenally immediately after emptying. In a rat model of clamping/release (C/R), the abdominal aorta was clamped for 2h after a single oral dose of tadalafil and then the clamp was released. BBF in O/E and C/R rats and PBF in C/R rats were measured by laser Doppler flow imaging. BBF decreased on overdistension and partially recovered after emptying. A progressive decrease in BBF was observed after O/E, and this was prevented by tadalafil treatment. Both BBF and PBF decreased during clamping of the abdominal aorta and partially recovered after clamp removal. Oral pretreatment with tadalafil partially or completely prevented the decreases in BBF and PBF not only after clamp removal but also during clamping. PDE5 mRNA was highly expressed in the bladder and the supporting vasculature. Tadalafil inhibited the O/E-induced decrease in BBF and the C/R-induced time-dependent decreases in BBF and PBF. PDE5 inhibition by tadalafil may improve both BBF and PBF.
authors.affiliation: Research Laboratories, Nippon Shinyaku Co., Ltd., 14, Nishinosho-monguchi-cho, Kisshoin, Minami-ku, Kyoto 601-8550, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Yoshinaga
authors.affiliation: Research Laboratories, Nippon Shinyaku Co., Ltd., 14, Nishinosho-monguchi-cho, Kisshoin, Minami-ku, Kyoto 601-8550, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawai
authors.affiliation: Research Laboratories, Nippon Shinyaku Co., Ltd., 14, Nishinosho-monguchi-cho, Kisshoin, Minami-ku, Kyoto 601-8550, Japan. Electronic address: m.oka@po.nippon-shinyaku.co.jp.
authors.forename: Michiko
authors.initials: M
authors.lastname: Oka
authors.affiliation: Research Laboratories, Nippon Shinyaku Co., Ltd., 14, Nishinosho-monguchi-cho, Kisshoin, Minami-ku, Kyoto 601-8550, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Fuchikami
authors.affiliation: Research Laboratories, Nippon Shinyaku Co., Ltd., 14, Nishinosho-monguchi-cho, Kisshoin, Minami-ku, Kyoto 601-8550, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Oyama
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000601:surgery; D003250:Constriction; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007083:Iliac Artery / Q000378:metabolism; D059411:Lower Urinary Tract Symptoms / Q000188:drug therapy*; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D011467:Prostate / Q000098:blood supply / Q000187:drug effects; D051381:Rats; D012669:Seminal Vesicles / Q000378:metabolism; D000068581:Tadalafil / Q000494:pharmacology* / Q000627:therapeutic use*; D001743:Urinary Bladder / Q000098:blood supply / Q000187:drug effects; D014551:Urinary Tract / Q000098:blood supply* / Q000187:drug effects*
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D000068581:Tadalafil; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5
keywords: Benign prostatic hyperplasia; Bladder; Blood flow; Prostate; Tadalafil