Sa1362 Rectal Hyposensitivity and Slow Colonic Transit Are More Common in Patients With Outlet Obstruction by Balloon Expulsion Testing: A Retrospective Cohort Analysis

Abstract

G A A b st ra ct s along different steps of biosynthesis of these end products, and their antagonists on the basal IAS tone. These agents were given either individually or in certain combinations. Molecular mechanisms for the IAS tone via these pathways were tracked down by monitoring RhoA/ROCK signal transduction cascade. Activation of RhoA/ROCK was monitored using translocation of these molecular proteins in particulate fractions. Results: U46619, a stable analog of TXA2, PGF2α and Ang II produced concentration (10-9 to 10-5 M)-dependent increase in the IAS tone. Interestingly, maximal increase in the IAS tone by U46619 and PGF2α was 98.5 ± 1.5% and 65.0 ± 6.0% maximal respectively, while increase in the IAS tone by Ang II was limited to 19.1 ± 2.8%. These increases in IAS tone were significantly higher than those in the RSM (p < 0.05; n = 6 to 8). Data further showed characteristically higher expression of biosynthetic enzymatic machineries of RAS and AA pathways in the IAS as compared with the RSM. Additionally, specific inhibition of AA pathway caused ~80% decrease in the IAS tone, while that of RAS produced only ~20% decrease. Signal transduction studies revealed that the end products of both AA and RAS pathways cause increase in IAS tone via activation of RhoA/ROCK. Conclusion: Activation of arachidonic acid (AA) and renin-angiotensin system (RAS) pathways both increase basal tone in the internal anal sphincter (IAS). The AA pathway is more potent activator of the IAS tone than the RAS pathway. Both the RAS and AA pathways lead to synthesis and release the end products (TXA2, PGF2α, and Ang II, respectively), which in turn activate their respective G-protein-coupled receptors TPR, FPR, and AT1-R. This activation provides extracellular signals which activate RhoA/ROCK for the maintenance of the basal tone in human IAS. These studies were supported by the NIH grant (RO1DK035385).