title: Effect of Silodosin, an Alpha1A-Adrenoceptor Antagonist, on Ventral Prostatic Hyperplasia in the Spontaneously Hypertensive Rat.
abstract: BACKGROUND
  A decreased prostatic blood flow could be one of the risk factors for benign prostatic hyperplasia/benign prostatic enlargement. The spontaneously hypertensive rat (SHR) shows a chronic prostatic ischemia and hyperplastic morphological abnormalities in the ventral prostate. The effect of silodosin, a selective alpha1A-adrenoceptor antagonist, was investigated in the SHR prostate as a prostatic hyperplasia model focusing on prostatic blood flow.
  
  
  METHODS
  Twelve-week-old male SHRs were administered perorally with silodosin (100 μg/kg/day) or vehicle once daily for 6 weeks. Wistar Kyoto (WKY) rats were used as normotensive controls and were treated with the vehicle. The effect of silodosin on blood pressure and prostatic blood flow were estimated and then the prostates were removed and weighed. The tissue levels of malondialdehyde (MDA), interleukin-6 (IL-6), chemokine (C-X-C motif) ligand 1/cytokine-induced neutrophil chemoattractant 1 (CXCL1/CINC1), tumor necrosis factor-alpha (TNF-α), transforming growth factor beta 1 (TGF-β1), basic fibroblast growth factor (bFGF) and alpha-smooth muscle actin (α-SMA) were measured. The histological evaluation was also performed by hematoxylin and eosin staining.
  
  
  RESULTS
  There was a significant increase in blood pressure, prostate weight, prostate body weight ratio (PBR), tissue levels of MDA, IL-6, CXCL1/CINC1, TNF-α, TGF-β1, bFGF and α-SMA in the SHR compared to the WKY rat. The ventral prostate in the SHR showed the morphological abnormalities compared to the WKY rat. Prostatic blood flow was decreased in the SHR. However, treatment with silodosin significantly restored the decreased prostatic blood flow in the SHR. Moreover, silodosin normalized tissue levels of MDA, IL-6, CXCL1/CINC1, TNF-α, TGF-β1, bFGF and α-SMA, and it ameliorated ventral prostatic hyperplasia in the SHR excluding blood pressure. Silodosin decreased PBR but not prostate weight in the SHR.
  
  
  CONCLUSIONS
  Silodosin can inhibit the progression of prostatic hyperplasia through a recovery of prostatic blood flow.
authors: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors: Shogo
authors: S
authors: Shimizu
authors: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors: Takahiro
authors: T
authors: Shimizu
authors: Department of Surgery, Division of Urology, Tottori University School of Medicine, Yonago, Japan.
authors: Panagiota
authors: P
authors: Tsounapi
authors: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors: Youichirou
authors: Y
authors: Higashi
authors: Department of Urology, Yale University School of Medicine, New Haven, CT, United States of America.
authors: Darryl T
authors: DT
authors: Martin
authors: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors: Kumiko
authors: K
authors: Nakamura
authors: Department of Surgery, Division of Urology, Tottori University School of Medicine, Yonago, Japan.
authors: Masashi
authors: M
authors: Honda
authors: Department of Urology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors: Keiji
authors: K
authors: Inoue
authors: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors: Motoaki
authors: M
authors: Saito
mesh_terms: D000199:Actins / Q000378:metabolism; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D054360:Chemokine CXCL1 / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011467:Prostate / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000199:Actins; D058668:Adrenergic alpha-1 Receptor Antagonists; D054360:Chemokine CXCL1; D016222:Fibroblast Growth Factor 2; D007211:Indoles; D015850:Interleukin-6; D008315:Malondialdehyde; D018340:Receptors, Adrenergic, alpha-1; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C513297:Cxcl1 protein, rat; C498862:Acta2 protein, rat; C095285:silodosin