Characterization of silodosin and naftopidil in the treatment of bladder dysfunction in the spontaneously hypertensive rat.
OBJECTIVE
As increasing evidence suggest that α(1)-blockers prevent benign prostatic hyperplasia related overactive bladder and nocturia in the human, we investigated the effects of silodosin and naftopidil on hypertension-related bladder dysfunction in the spontaneously hypertensive rat (SHR) model.


METHODS
Twelve-week-old male SHRs received no treatment or treatment with silodosin (100 µg/kg, p.o.) or naftopidil (10 or 30 mg/kg, p.o.) once daily for 6 weeks. Wistar rats were used as normotensive controls. After 6-week treatment, voiding functions were estimated by metabolic cages (dark- and light-cycle separately) and cystometric studies. Furthermore, the bladder blood flow (BBF) was measured employing the hydrogen clearance method.


RESULTS
SHRs showed significant increases in micturition frequency, and decreases in BBF and single voided volume in both metabolic cages and cystometrograms compared to the Wistar group. Treatment with silodosin normalized the decreased BBF, and treatment with naftopidil increased the BBF in a dose-dependent manner in the SHR group. Although treatment with silodosin and the high dose of naftopidil significantly inhibited micturition frequency in one day, only treatment with the high dose of naftopidil significantly inhibited micturition frequency and urine production in the light-cycle compared to the non-treated SHRs. Although treatment with silodosin and the high dose of naftopidil significantly increased single voided volume, only treatment with silodosin significantly inhibited non-voiding contractions in the cystometrgrams.


CONCLUSIONS
Our data suggest that both silodosin and naftopidil improve hypertension-related bladder dysfunction in the SHR, and naftopidil but not silodosin improves urinary frequency in the light-cycle due to inhibition of urine production.
Division of Molecular Pharmacology, Tottori University School of Medicine, Yonago, Japan. saitomo@med.tottori-u.ac.jp
Motoaki
M
Saito
Shogo
S
Shimizu
Fumiya
F
Ohmasa
Ryo
R
Oikawa
Panagiota
P
Tsounapi
Fotios
F
Dimitriadis
Yukako
Y
Kinoshita
Keisuke
K
Satoh
D058668:Adrenergic alpha-1 Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D002940:Circadian Rhythm; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009281:Naphthalenes / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D010879:Piperazines / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology; D001745:Urinary Bladder Diseases / Q000188:drug therapy*; D014554:Urination
D058668:Adrenergic alpha-1 Receptor Antagonists; D007211:Indoles; D009281:Naphthalenes; D010879:Piperazines; C095285:silodosin; C064357:naftopidil