Login to Access Video or Poster Abstract: MP26-20
Sources of Funding: None

Introduction

Decreased serum estrogen is known to cause lower urinary tract symptoms. Adenosine triphosphate (ATP) is considered to be a bioactive substance that modulates bladder function. The purpose of this study was to assess changes in purinergic regulation systems in the bladder wall, including ATP released from the urothelium, using an ovariectomy model.

Methods

Twenty female guinea pigs (weight: 450-550 g) were divided into an ovariectomy group (OVX; n=10), which received bilateral ovariectomy to induce surgical menopause, and a sham operation group (Sham; n=10). All animals were housed in metabolic cages for 24 hours at 4 weeks after the operation. An intact strip, which contains the whole bladder layer, was stimulated by purinergic agents (e.g., ATP, α,β-methylene ATP, ADP), carbachol (CCh; 10^-8 M to 10^-5 M), and by electrical field stimulation (EFS; 1-40 Hz, duration 0.5 msec). Mucosal strips including urothelium were prepared by dissection between the suburothelial and detrusor layers. The concentration of ATP perfusing through the strips was measured using a luciferine-luciferase assay.

Results

The serum β-estradiol level was significantly lower in the OVX group, and uterine weight was less in the OVX group (OVX 227.4, Sham 1475 mg, p<0.001). In the OVX group, 24-hour urination frequency increased, and the mean voided urine volume decreased. 10 mN of passive stretch of mucosal strips increased the ATP concentration in both groups, and the rate of increase was significantly higher in the OVX group (226.5%) than in the Sham group (127.6%). Since the response to CCh in intact strips was significantly smaller in the OVX group (pEC₅₀; 6.21) than in the Sham group (6.36), the contractile response to ATP was higher in the OVX group (10^-3 M: Sham 787.0, OVX 986.6 mN/g). Contractile responses to 10^-4 M ADP and 10^-5 M α,β-methylene ATP were also larger in the OVX group. Although the total contractile response to EFS was similar in both groups, atropine-resistant contraction was increased in the OVX group (24 Hz: Sham 39.2, OVX 58.7% normalized by Tmax). Moreover, the correlation coefficient between the tension of intact strips stimulated by EFS and ATP release from them was larger in the OVX group than in the Sham group (4 Hz: r²= Sham 0.342, OVX 0.578).

Conclusions

Detrusor contractility to CCh decreased in the OVX group, though the purinergic system for bladder contraction and ATP release were upregulated in the OVX group. It appeared that the purinergic system compensated for bladder contractility. Increasing ATP release from the mucosa may upregulate bladder sensation.

Funding

None