title: Protective effects of the selective alpha1A-adrenoceptor antagonist silodosin against cyclophosphamide-induced cystitis in rats.
abstract: We investigated the protective effects of a selective α1A-adrenoceptor antagonist, silodosin (Silod) on urinary bladder function in cyclophosphamide (CYP)-induced cystitis rats, with and without desensitization of the capsaicin (CAP)-sensitive afferent nerve pathway. Male Wistar rats (310-400 g) were pretreated with Silod (0, 100, or 300 μg/kg/day, p.o.) for 1 week before cystometry, and were administered either CYP (150 mg/kg, i.p.) or saline 2 days before the experiment. In another experiment, the rats were treated with CAP (125 mg/kg, s.c.) 4 days before the cystometry. The rat bladders were harvested, weighed, and evaluated histologically. The cystometric evaluation showed significant reductions in the intercontraction interval (ICI), single voided volume (SVV), and bladder compliance in CYP-treated rats compared to those in the vehicle-treated rats. High-dose Silod or CAP treatment significantly increased the ICI and SVV in the CYP rats. However, high-dose Silod treatment did not increase the ICI and SVV in CAP-treated CYP rats. Treatment with Silod did not improve the bladder weight, edema, and leukocyte infiltration resulting from the CYP-induced bladder inflammation. These data suggest that blockade of α1-adrenoceptors by Silod inhibited the CAP-sensitive afferent pathway in rats with cystitis.
authors.affiliation: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors.forename: Nanxi
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Japan. Electronic address: shimizu-sh@kochi-u.ac.jp.
authors.forename: Shogo
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors.forename: Youichirou
authors.initials: Y
authors.lastname: Higashi
authors.affiliation: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors.forename: Motoaki
authors.initials: M
authors.lastname: Saito
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003520:Cyclophosphamide; D003556:Cystitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D007211:Indoles; D015850:Interleukin-6; D020011:Protective Agents; D003520:Cyclophosphamide; C095285:silodosin; D009195:Peroxidase
keywords: Afferent nerve pathway; Alpha 1A-adrenoceptor antagonist; Cyclophosphamide-induced cystitis; Intercontraction interval; Silodosin