Does pig urothelium derived inhibitory factor (UDIF) inhibit rat aorta contractility?

Rebecca L. Cross1, Christopher R. Chapple2 and Russell Chess-Williams1. 1Department of Biomedical Science, University of Sheffield, 2Dept. of Urology, Royal Hallamshire Hospital, Sheffield.

The presence of urothelium inhibits maximal bladder contractions by approximately 50% in response to carbachol in pig and human isolated muscle strips (Hawthorn et al., 2000, Chaiyaprasithi et al., 2003). This inhibitory effect has been attributed to release of a diffusible urothelium derived inhibitory factor (UDIF). The aim of this study is to discover whether urothelium-intact detrusor strips from the pig bladder can inhibit rat aorta smooth muscle contractions to phenylephrine.

Circular aortic strips from female Wistar rats (250-300g), with the endothelium removed were set up under 1g tensions in gassed Krebs bicarbonate solution at 37°C. Cumulative phenylephrine concentration-response curves were obtained in the absence and presence of pig detrusor strips, (denuded and urothelium intact) and with or without 30µM carbachol present. Some experiments were performed in the presence of 5 µM indomethacin and 100 µM L-NNA. Results are expressed as the mean ± sem, with paired Student’s t-test used for statistical analysis.

The presence of urothelium-intact or denuded detrusor strips in the absence of 30 µM carbachol did not significantly inhibit aortic contractions, with maximum contractions of 93.8 ± 21.5%, (n=8) and 96.2 ± 12.7% (n=7) of their control, respectively (figure 1). 30 µM carbachol alone did not cause the inhibition of aortic contractions (maximal contraction is 105.2 ± 13% of control, n=5, figure 2), nor did it relax phenylephrine precontracted aorta strips (n=31).

However urothelium-intact detrusor strips in the presence of 30 µM carbachol significantly inhibited rat aorta maximal contractions to phenylephrine by 21.8 ± 8.2% (n=7, p=0.04, figure 3). Although denuded detrusor strips in the presence of 30 µM carbachol did not inhibit aortic contractions (maximal contraction is 108.7 ± 15% of control, n=5, figure 3). The inhibition caused by the intact detrusor strip in the presence of 30 µM carbachol was not blocked by 5 µM indomethacin and 100 µM L-NNA, (25.7 ± 10.5% inhibition, n=7, p=0.04, figure 4).

The release of a diffusible inhibitory factor from pig bladder urothelium attenuates maximal contractions of rat aorta strips to phenylephrine. The inhibition is dependent upon the presence of carbachol and is not due to the release of nitric oxide or a cyclo-oxygenase product.

Chaiyaprasithi B. et al (2003) J Urol., 170, 1897-1900.
Hawthorn M. et al. (2000) Br. J. Pharmacol., 129, 416-19.