ABSTRACT: Bladder stretch has been implicated in the development of the sensations associated with urgency in women with overactive bladder (OAB). It is well established that bladder stretch causes release of ATP from urothelial cells. Some investigators have hypothesized that ATP release may modulate initial afferent sensation in OAB patients whose main symptom is urinary urgency. Animal studies conducted in vitro showed that, in addition to stretch, urine acid was a potent stimulant of ATP release. Moreover, in a human study, women with detrusor overactivity had significantly lower urinary pH than a control. It is possible that increased urine acidity could contribute to urgency, possibly through release of ATP.
This study tested the hypothesis that ATP plays an important role in women with OAB characterized by symptoms of urgency and that low urine pH in these patients may be associated with symptoms of frequency and/or urgency. The correlation between ATP release, urine pH, and urodynamic parameters was investigated in women with OAB characterized by small bladder volumes at first desire to void (FDV) and maximal cystometric capacity (MCC). All subjects had symptoms of frequency/urgency (mild bladder pain syndrome). Routine cystometry was performed in a consecutive series of 246 women aged 28 to 87 years. Control subjects were 69 women with normal bladder function or with pure urodynamic stress incontinence without urge symptoms, voiding dysfunction, or urinary infection. A sample of the voided urodynamic fluid was collected and stored at 20°C. ATP was measured using bioluminescence. A catheter urine specimen was collected for measurement of pH. Linear regression analysis was used to test correlations between ATP and urine pH.
Patients with voiding dysfunction, urinary tract infection, and detrusor overactivity were excluded from the study. There was a strong inverse correlation between ATP concentration in voided urodynamic fluid and FDV (r2 = 0.25; P = 0.01) in OAB patients (n = 25). In contrast, no such correlation was seen for MCC or in control subjects. In women with OAB, but not control subjects, a significant inverse correlation (r2 = 0.16; P = 0.047) was found between ATP concentration in voided urodynamic fluid and urinary pH. However, no correlation between urine pH and MCC occurred in patients with OAB.
These data suggest that ATP is an important factor in patients with OAB for initial perception of need to urinate, which often produces the symptom of urgency/frequency. Increasing ATP concentration in patients with OAB (at FDV) was directly related to the increasing acidity of the urine.
Department of Urogynaecology, St George Hospital, University of New South Wales, Sydney (Y.C., W.A., K.H.M); Graduate School of Medicine, University of Wollongong, Wollongong (K.J.M.); and Department of Urology, Prince of Wales Hospital (R.J.M.), and Department of Pharmacology, School of Medical Sciences (E.B.), University of New South Wales, Sydney, New South Wales, Australia