Int Neurourol J.  2018 Mar;22(1):20-29. 10.5213/inj.1836064.032.

Add-on Therapy With the α-Blockers Tamsulosin and Naftopidil Improves Voiding Function by Enhancing Neuronal Activity in Prostatic Hyperplasia Rats

Affiliations
  • 1Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.
  • 2Department of Anesthesiology and Pain Medicine, Kyung Hee Medical Center, Kyung Hee University College of Medicine, Seoul, Korea.
  • 3Department of Internal Medicine, Kyung Hee University Hospital at Gandong, Kyung Hee University College of Medicine, Seoul, Korea.
  • 4Department of Urology, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea. cst326@paran.com

Abstract

PURPOSE
Benign prostatic hyperplasia (BPH) impacts quality of life in men by causing lower urinary tract symptoms. α1-Adrenoceptor (α1-AR) blockers improve lower urinary tract symptoms. We investigated the efficacy of add-on therapy with α1-AR blockers on BPH rats.
METHODS
Rats in the drug-treated groups were orally administered each drug once a day for 30 days after orchiectomy. To induce BPH, rats were castrated and testosterone (20 mg/kg) was injected subcutaneously once per day for 30 days. Cystometry was conducted to measure voiding contraction pressure and the interval contraction time, immunohistochemistry was performed to measure c-Fos and nerve growth factor (NGF) expression in the neuronal voiding centers, and nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry was used to measure nitric oxide synthase (NOS) expression.
RESULTS
Orchiectomy and testosterone injection decreased voiding contraction pressure and the interval contraction time, suggesting BPH symptoms. Voiding contraction pressure and the interval contraction time were greater in the group that received the combination treatment (tamsulosin with naftopidil) than in the tamsulosin monotherapy or naftopidil monotherapy groups. c-Fos, NGF, and NOS expression in the neuronal voiding centers was enhanced by BPH induction. c-Fos, NGF, and NOS expression was suppressed by the combination treatment (tamsulosin with naftopidil) to a greater extent than was the case for tamsulosin monotherapy or naftopidil monotherapy.
CONCLUSIONS
Combination therapy of tamsulosin and naftopidil showed greater efficacy for the treatment of BPH than tamsulosin monotherapy or naftopidil monotherapy; therefore, combination therapy can be considered as a novel therapeutic method for BPH.

Keyword

Prostatic hyperplasia; Combined therapy; Neuronal voiding center; c-fos; Nerve growth factor; Nitric oxide synthase

MeSH Terms

Animals
Humans
Immunohistochemistry
Lower Urinary Tract Symptoms
Male
Methods
NAD
Nerve Growth Factor
Neurons*
Nitric Oxide Synthase
Orchiectomy
Prostatic Hyperplasia*
Quality of Life
Rats*
Testosterone
NAD
Nerve Growth Factor
Nitric Oxide Synthase
Testosterone
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