Abstract: PD70-12
Sources of Funding: none

Introduction

Cold stress produced by sudden change or continuous exposure to low temperature exacerbates lower urinary tract symptoms (LUTS), such as urinary urgency, frequency, and nocturia. Stimulation of C-fibers and TRPM8 channels have been reported as mechanisms of cold stress related LUTS. Menopause women are known to be sensitive to cold stress, but the mechanism is not clearly known. The aim of this study is to show that menopause causes impairment of micro blood flow in the bladder mucosa and dermis under the skin and up-regulates TRPM8 channels which induces cold stress related frequency in rats.

Methods

A total of 18 Spontaneously Hypertensive rats at postnatal week 10 were used in the experiments. The rats were randomly divided into 2 groups, including 9 with sham operation and 9 with bilateral ovariectomy. At 4 weeks after surgery, cystometography (CMG) was performed. CMG was first performed in room temperature (RT) for 20 minuets. Rats were then put into low temperature (LT) for 40 minutes. After LT, rats were put into RT for 20 minutes. After CMG, the whole bladder and dermis under the lumbar skin was harvested and real-time RT-PCR was performed. Immunohistochemistry was also performed and impairment of micro blood flow was evaluated by hypoxia-inducible factor-1 (HIF-1) staining.

Results

Results of the CMG are shown in Fig 1. Basal pressure and micturition pressure did not show a difference between control rats and ovariectomy rats, but change rate with cold stress in voiding interval and micturition volume showed a significant exacerbate. Results of real-time RT-PCR are shown in Fig 2. Up-regulation of TRPM8 in the dermis and TRPV1 in the bladder mucosa was seen in ovariectomy rats. Immunohistochemistry showed increase of HIF-1 in the bladder mucosa and dermis.

Conclusions

Ovariectomy causes impairment of micro blood flow in the bladder mucosa and dermis which induces cold stress frequency by up-regulating TRPM8 channels.

Funding

none