Karl-Erik Andersson led the peer-review process as the Associate Editor responsible for the paper.
Olmesartan ameliorates urinary dysfunction in the spontaneously hypertensive rat via recovering bladder blood flow and decreasing oxidative stress
Article first published online: 17 JUN 2013
© 2013 Wiley Periodicals, Inc.
Neurourology and Urodynamics
Volume 33, Issue 3, pages 350–357, March 2014
How to Cite
Shimizu, S., Saito, M., Oiwa, H., Ohmasa, F., Tsounapi, P., Oikawa, R., Dimitriadis, F., Martin, D. T., Satoh, I., Kinoshita, Y. and Tomita, S. (2014), Olmesartan ameliorates urinary dysfunction in the spontaneously hypertensive rat via recovering bladder blood flow and decreasing oxidative stress. Neurourol. Urodyn., 33: 350–357. doi: 10.1002/nau.22405
Conflict of interest: none.
Shogo Shimizu, Motoaki Saito, and Harunori Oiwa have equally contributed to this study.
- Issue published online: 15 MAR 2014
- Article first published online: 17 JUN 2013
- Manuscript Accepted: 8 MAR 2013
- Manuscript Received: 18 DEC 2012
- Ministry of Education, Science, and Culture of Japan. Grant Numbers: 20591880, 24592431
- bladder blood flow;
- bladder dysfunction;
- spontaneously hypertensive rat
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).
Materials and 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.
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.
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. Neurourol. Urodynam. 33:350–357, 2014. © 2013 Wiley Periodicals, Inc.