PURPOSE: Obstructive sleep apnea (OSA) has been associated with voiding symptoms in humans and animals, yet it's effects on the urinary tract are poorly understood.
We examined bladder structure and function, markers of oxidative damage, and the redox survival pathway in a rat model of OSA to identify changes.
MATERIALS AND METHODS: To model OSA, a rat oxycycler system was used to create cyclical interruption in breathing oxygen, thereby producing intermittent hypoxemia. Male Sprague-Dawley rats were divided into treatment (OSA, n=8), sham (n=8) and control (n=8) groups. After 8 weeks exposure to OSA conditions, the day and night voiding behavior of rats was assessed in metabolic cages then cystometrograms were obtained and bladder tissue processed for biochemical assays, ELISA and TEM.
RESULTS: Animals exposed to OSA conditions developed increased urinary frequency and increased total urine output. Cystometric changes included detrusor instability, bladder non-compliance, and increased spontaneous contractions. These changes were associated with bladder oxidative stress characterized by significant increases in tissue levels of malondialdehyde and advanced oxidation protein products. OSA activated cell survival signaling manifested by increased expression of PI3K and phosphorylated Akt1. TEM showed marked ultrastructural damage of the subcellular elements.
CONCLUSION: Intermittent hypoxia in OSA causes oxidative stress with ultrastructural and functional changes in the bladder. OSA-related nocturia/voiding symptoms could be the result of these direct changes. Untreated OSA has significant health consequences. Identifying urinary oxidative stress products in patients with nocturia may be useful as an economic noninvasive biomarker for the identification of undiagnosed OSA.
Written by:
Witthaus MW, Nipa F, Yang JH, Li Y, Lerner LB, Azadzoi KM. Are you the author?
Urology Fellow, Department of Urology, VA Boston Healthcare System and Boston University School of Medicine, Boston, Massachusetts; Research Associate, Department of Urology, VA Boston Healthcare System and Boston University School of Medicine, Boston, Massachusetts; Department of Urology, VA Boston Healthcare System and Boston University School of Medicine, Boston, Massachusetts; Department of Urology and Department of Pathology, VA Boston Healthcare System and Boston University School of Medicine, Boston, Massachusetts.
Reference: J Urol. 2014 Nov 15. pii: S0022-5347(14)04901-5.
doi: 10.1016/j.juro.2014.11.055
PubMed Abstract
PMID: 25463994