title: Olmesartan ameliorates urinary dysfunction in the spontaneously hypertensive rat via recovering bladder blood flow and decreasing oxidative stress.
abstract: OBJECTIVE
  As hypertension (HT) is one of the risk factors for lower urinary tract symptoms, we investigated the effect of an angiotensin II type I receptor blocker, olmesartan, on bladder dysfunction in the spontaneously hypertensive rat (SHR).
  
  
  METHODS
  Twelve-week-old male SHRs were administered perorally with olmesartan (0, 1, or 3 mg/kg/day) or nifedipine (30 mg/kg/day) for 6 weeks. Wistar rats were used as normotensive controls. The effects of olmesartan or nifedipine on blood pressure (BP), bladder blood flow (BBF), urodynamic parameters, tissue levels of malondialdehyde (MDA), nuclear factor erythroid 2-related factor 2 (Nrf2), and nerve growth factor (NGF) were measured in the bladder. Localization of 4-hydroxy-2-nonenal (4-HNE), Nrf2, and NGF in the bladder was shown by immunohistochemistry.
  
  
  RESULTS
  The SHRs showed significant increase in BP, micturition frequency, and expression of MDA, 4-HNE, Nrf2, and NGF when compared to the control Wistar rats. Conversely, there was a decrease in BBF and single voided volume in SHRs when compared to Wistar rats. Treatment with olmesartan and nifedipine significantly improved BP. However, only olmesartan significantly ameliorated urodynamic parameters and oxidative damage compared to the non-treated SHR. The immunoreactivities of 4-HNE, Nrf2, and NGF in SHR urothelium and blood vessels were increased compared to the control. Treatment with a high dose of olmesartan decreased the expressions of 4-HNE, Nrf2, and NGF in the bladder.
  
  
  CONCLUSIONS
  Our data suggest that BP, BBF, and oxidative stress may be responsible for the functional changes in HT-related bladder dysfunction. Olmesartan significantly ameliorated this bladder dysfunction.
authors.affiliation: Division of Molecular Pharmacology, Tottori University School of Medicine, Yonago, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Shimizu
authors.forename: Motoaki
authors.initials: M
authors.lastname: Saito
authors.forename: Harunori
authors.initials: H
authors.lastname: Oiwa
authors.forename: Fumiya
authors.initials: F
authors.lastname: Ohmasa
authors.forename: Panagiota
authors.initials: P
authors.lastname: Tsounapi
authors.forename: Ryo
authors.initials: R
authors.lastname: Oikawa
authors.forename: Fotios
authors.initials: F
authors.lastname: Dimitriadis
authors.forename: Darryl T
authors.initials: DT
authors.lastname: Martin
authors.forename: Itaru
authors.initials: I
authors.lastname: Satoh
authors.forename: Yukako
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: Shuhei
authors.initials: S
authors.lastname: Tomita
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology*; D001743:Urinary Bladder / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001745:Urinary Bladder Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D014563:Urodynamics / Q000187:drug effects
chemical_list: D000447:Aldehydes; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D015415:Biomarkers; D007093:Imidazoles; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D013777:Tetrazoles; D008315:Malondialdehyde; C437965:olmesartan; D020932:Nerve Growth Factor; D009543:Nifedipine; C027576:4-hydroxy-2-nonenal
keywords: bladder blood flow; bladder dysfunction; olmesartan; spontaneously hypertensive rat