Functional roles of TRPV1 channels in lower urinary tract irritated by acetic acid: in vivo evaluations of the sex difference in decerebrate unanesthetized mice

Abstract

Sex-specific differences in activity of the lower urinary tract (LUT) responding to acid irritation in mice have been revealed. This study, using continuous infusion cystometry with acetic acid (AA; pH 3.0), was conducted to examine whether the transient receptor potential vanilloid type 1 (TRPV1) channels expressed in the mouse LUT are involved in the sex difference in functional responses of the bladder and urethra to irritation. No differences were found between effects of capsazepine (a TRPV1 blocker; 100 microM) and those of its vehicle on any of the cystometric changes by intravesical AA in either female or male mice. However, capsazepine eliminated the acid-induced sex differences in parameters associated with bladder contraction phase (i.e., maximal voiding pressure, closing peak pressure, 2nd-phase contraction, bladder contraction duration), whereas capsazepine did not affect those in parameters associated with bladder-filling period (i.e., intercontraction interval, actual collecting time). In males, capsazepine reduced the number of bladder contractions accompanying fluid dribbling at 2nd-phase contraction, which is indicative of the urethral response to irritation, whereas in females it increased the number. Together, these results suggest the possibilities that TRPV1 channels in the bladder and urethra are involved in the sex difference in the LUT response to acid irritation and that these participate, e.g., via "cross talk" between the bladder and urethra, in the fine-tuning of intravesical pressure (or bladder emptying) at the bladder contraction phase under irritated LUT conditions but not in sensing for bladder filling during the storage period, although the contribution of the mechanism may be small.