Sex differences in the role of urothelium in rat bladder contractile function

Bladder dysfunction is a prevalent condition associated with diabetes, aging, and cardiovascular disease. Despite sex differences in the risk factors, clinical findings and prevalence of diseases associated with bladder dysfunction, the role of sex differences in the physiological regulation of bladder function has been poorly investigated. We have previously observed that contractile responses to both carbachol (CCh) and electrical field stimulation (EFS) were greater in the male than the female rat bladder segments in both the presence and absence of urothelium. We hypothesized that sex differences in the role of urothelium in bladder contraction may underlie the sex differences observed clinically in bladder dysfunction. Female and male rat bladder contractile responses to CCh were measured in the presence and absence of the cyclooxygenase (COX) inhibitor indomethacin and the nitric oxide synthase (NOS) inhibitor L‐NAME, and in the presence and absence of urothelium. We observed that the presence of urothelium inhibited CCh‐induced contraction in the bladder, and this inhibitory effect was larger in the female than the male bladder (ΔEmax CCh[−Uro +Uro] (mN/mg) female=1.38±0.58, male=0.53±0.31). Incubation of bladder segments with indomethacin reverted the inhibitory effect of urothelium on CCh‐induced contraction in the male, but not the female bladder. Incubation of bladder segments with both indomethacin and L‐NAME reverted the inhibitory effect of urothelium on CCh‐induced contraction in bladder segments from both sexes. Our data suggest that there are sex differences in the physiological contractile function of the rat bladder in basal conditions, and that the contribution of COX to urothelium‐mediated contractile mechanisms is greater in the male than the female. Support or Funding Information NIDDK Diabetic Complications Consortium (DiaComp, www.diacomp.org ), grant DK076169.