title: Effect of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid on the intraurethral pressure in a rat model of benign prostatic hyperplasia.
abstract: OBJECTIVE
  To investigate the effect of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid, a new benzofuroindole derivative, on the intraurethral pressure in a rat model of benign prostatic hyperplasia.
  
  
  METHODS
  Benign prostatic hyperplasia was induced by testosterone and 17β-estradiol, which were administered intramuscularly once a day for 12 weeks. The effects of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid and tamsulosin on the intraurethral pressure induced by the electrostimulation of hypogastric nerves after a single intravenous injection of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid (10 mg/kg) or tamsulosin (10 μg/kg) were evaluated in a benign prostatic hyperplasia model. The electrostimulation-induced intraurethral pressure was measured just before and after the injection of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid. Bodyweight and genitourinary organ weights were recorded, and serums and tissues were subjected to hormone assays and histopathology. In addition, the expression of α1-adrenoceptors in the prostate was measured by western blotting.
  
  
  RESULTS
  The benign prostatic hyperplasia groups showed increased prostatic index, increased concentrations of testosterone, free testosterone and estradiol in serum, and increased epithelial thickness of the prostate. An injection of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid or tamsulosin significantly inhibited the elevation of electrostimulation-induced intraurethral pressure. In addition, 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid did not cause a significant change in the blood pressure compared with tamsulosin. While the benign prostatic hyperplasia group showed increased the expression of α1-adrenoceptors, the 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid or tamsulosin injection into a rat model of benign prostatic hyperplasia decreased the expression of α1-adrenoceptors.
  
  
  CONCLUSIONS
  These findings show that 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid might be beneficial for lowering the intraurethral pressure associated with benign prostatic hyperplasia, and it could represent a therapeutic option for benign prostatic hyperplasia patients.
authors.affiliation: Department of Urology, Chonbuk National University and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University, Jeonju, Korea.
authors.forename: Bo Ram
authors.initials: BR
authors.lastname: Choi
authors.affiliation: Department of Urology, Chonbuk National University and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University, Jeonju, Korea.
authors.forename: Kiran Kumar
authors.initials: KK
authors.lastname: Soni
authors.affiliation: Department of Urology, Chonbuk National University and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University, Jeonju, Korea.
authors.forename: Li Tao
authors.initials: LT
authors.lastname: Zhang
authors.affiliation: Department of Urology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Insuk
authors.initials: I
authors.lastname: So
authors.affiliation: Department of Urology, Chonbuk National University and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University, Jeonju, Korea.
authors.forename: Hye Kyung
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Urology, Chonbuk National University and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University, Jeonju, Korea.
authors.forename: Jong Kwan
authors.initials: JK
authors.lastname: Park
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004958:Estradiol / Q000097:blood / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D011312:Pressure; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D000077409:Tamsulosin; D014521:Urethra / Q000187:drug effects*
chemical_list: C540673:4-chloro-7-trifluoromethyl-10H-benzo(4,5)furo(3,2-b)indole-1-carboxylic acid; D001572:Benzofurans; D007211:Indoles; D018340:Receptors, Adrenergic, alpha-1; D013449:Sulfonamides; D004958:Estradiol; D000077409:Tamsulosin
keywords: 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid; benign prostatic hyperplasia; electrostimulation; hypogastric nerve; intraurethral pressure