Interstitial cells of Cajal (ICCs) have been identified as pacemaker cells in the upper urinary tract and urethra, but the role of ICCs in the bladder remains to be determined. We tested the hypotheses that ICCs express cyclooxygenase (COX), and that COX products (prostaglandins), are the cause of spontaneous rhythmic contraction (SRC) of isolated strips of rabbit bladder free of urothelium. SRC was abolished by 10 μM indomethacin and ibuprofen (non-selective COX inhibitors). SRC was concentration-dependently inhibited by selective COX-1 (SC-560 and FR-122047) and COX-2 inhibitors (NS-398 and LM-1685), and by SC-51089, a selective antagonist for the PGE-2 receptor (EP) and ICI-192,605 and SQ-29,548, selective antagonists for thromboxane receptors (TP). The partial agonist/antagonist of the PGF-2α receptor (FP), AL-8810, inhibited SRC by ∼50%. Maximum inhibition was ∼90% by SC-51089, ∼80–85% by the COX inhibitors and ∼70% by TP receptor antagonists. In the presence of ibuprofen to abolish SRC, PGE-2, sulprostone, misoprostol, PGF-2α and U-46619 (thromboxane mimetic) caused rhythmic contractions that mimicked SRC. Fluorescence immunohistochemistry coupled with confocal laser scanning microscopy revealed that c-Kit and vimentin co-localized to interstitial cells surrounding detrusor smooth muscle bundles, indicating the presence of extensive ICCs in rabbit bladder. Co-localization of COX-1 and vimentin, and COX-2 and vimentin by ICCs supports the hypothesis that ICCs were the predominant cell type in rabbit bladder expressing both COX isoforms. These data together suggest that ICCs appear to be an important source of prostaglandins that likely play a role in regulation of SRC. Additional studies on prostaglandin-dependent SRC may generate opportunities for the application of novel treatments for disorders leading to overactive bladder.

Study Type – Prognosis (cohort series)Level of Evidence 2bWhat's known on the subject? and What does the study add?Epidemiologic studies have shown that warmer climates are associated with increased incidence of nephrolithiasis. Many hypothesize that this is due to dehydration and lower urine volumes. The current study of stone formers reports that greater temperatures are associated with significant increases in urine calcium which may shed light on the mechanism underlying the increased stone incidence associated with increased ambient temperature.OBJECTIVE To understand the effects of temperature, humidity and season of year on 24‐h urine composition in patients with nephrolithiasis. PATIENTS AND METHOD A retrospective review was performed of patients evaluated at four metabolic stone clinics. Multivariate linear regression models examined the relationship between mean temperature, average humidity, season of year and 24‐h urine composition. Multivariate models adjusted for known risk factors for stone disease. Mean temperature and average humidity data were obtained from http://www.weatherunderground.com based on patient‐provided addresses. RESULTS A total of 599 patients were included in the study, comprising 239 women and 360 men with a mean age of 53.6 years (sd 15.0). Mean temperature was 16.9 °C (sd 4.8, range −21.1 to 38.3 °C) and average humidity was 58.1% (sd 23.5, range 11–100%). On multivariate linear regression, increasing temperature was associated with increasing urine calcium (β= 11.3, 95% CI 2.2–20.0), super‐saturation of calcium oxalate (β= 0.6, 95% CI 0.2–0.9), super‐saturation of calcium phosphate (β= 0.14, 95% CI 0.03–0.2), and decreasing urine sodium (β=−5.2, 95% CI −10.3 to −0.1). As seasons become warmer (i.e. from winter to autumn to spring to summer), changes were increased urine volume (β= 0.09, 95% CI 0.01–0.2) and decreased super‐saturation of calcium phosphate (β=−0.2, 95% CI −0.3 to −0.03). There were no associations between quintile of humidity and any 24‐h urine constituents. CONCLUSIONS Increasing temperature may increase stone risk by increasing urine excretion of calcium, and the super‐saturation of calcium oxalate and calcium phosphate. These findings were independent of humidity and of season of year. This appears to be related to a physiological impact of temperature itself, rather than to geographic location.

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Psychiatric comorbidities and sexual trauma are prevalent in female veterans presenting for evaluation of lower urinary tract symptoms and psychiatric comorbidities are associated with greater quality of life impact.

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