84,85 The authors suggested that internal iliac vessel remodeling induced by hypercholesterolemia and endothelial injuries play a role in the development of OAB. Furthermore, increased proinflammation cytokines and leukotrienes could
increase smooth muscle contraction and induce bladder hyperactivity. Selleck PF01367338 Hypertension, hyperinsulinemia and obesity are associated with autonomic hyperactivity. It is well-known that autonomic hyperactivity can induce bladder neck dysfunction and LUTS.86 Detrusor hypertrophy is another common phenomenon that can be observed in animal models of metabolic syndrome and diabetes.75,79,81 It has been shown that detrusor hypertrophy is concurrent with decreased functional bladder capacity and increase of urinary frequency in a fructose-fed rat model. Detrusor hypertrophy is ordinarily associated with poor compliance, high intravesical pressure as well as DO, which might reduce bladder blood flow significantly.87
It was followed by cyclic ischemia-reperfusion injuries, and increased reactive nitrogen species. Oxidative stress is induced by over- exercise of the detrusor in the course of repeat DO and urinary frequency.85,88 Mitochondrial apparatus could supply high-energy consumption in the early stages of bladder hyperactivity. In the long run, excessive energy demand and stimulation could exhaust the mitochondrial respiratory chain and impair its energy transduction system. Under such circumstances,
oxidatively strained mitochondria become deformed and turn to a source of reactive oxidative KU-57788 datasheet second stress, which initiates a self-destructing process in the mitochondrial respiratory apparatus, leading to protein damage, detrusor dysfunction, and ultimately atrophy. C-reactive protein (CRP) is produced and secreted by the liver in response to inflammatory processes occurring in the body. The association of elevated serum CRP with various lower urinary tract symptoms (LUTS) suggests a possible role of inflammation. Kupelian et al. analyzed data from 1898 men and 1854 women who participated in the Boston Area Community Health study and had complete data on CRP levels.89 They found the prevalence of OAB increased with CRP levels in both genders. Chuang et al. also showed that serum CRP level was significantly higher in OAB wet patients compared with control (2.96 ± 0.47 vs 0.93 ± 0.27 mg/L, P < 0.01) and OAB dry (2.96 ± 0.47 vs 1.06 ± 0.16 mg/L, P < 0.05).90 NGF plays a key role in the survival of sensory neurons during development and is necessary throughout adulthood for maintenance of the normal properties of small-sized afferent neurons with unmyelinated axons (i.e. C-fiber afferents). There is also growing evidence that NGF is a peripheral mediator of several types of inflammatory painful conditions.