Changes in murine anorectum signaling across the life course.

S Fidalgo,B A Patel,R N Ranson,M J Saffrey,M S Yeoman

doi:10.1111/nmo.13426

S Fidalgo, B A Patel + Show 3 more

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https://doi.org/10.1111/nmo.13426

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Abstract

BackgroundIncreasing age is associated with an increase in the incidence of chronic constipation and fecal impaction. The contribution of the natural aging process to these conditions is not fully understood. This study examined the effects of increasing age on the function of the murine anorectum.MethodsThe effects of increasing age on cholinergic, nitrergic, and purinergic signaling pathways in the murine anorectum were examined using classical organ bath assays to examine tissue function and electrochemical sensing to determine age‐related changes in nitric oxide and acetylcholine release.Key ResultsNitrergic relaxation increased between 3 and 6 months, peaked at 12 months and declined in the 18 and 24 months groups. These changes were in part explained by an age‐related decrease in nitric oxide (NO) release. Cholinergic signaling was maintained with age by an increase in acetylcholine (ACh) release and a compensatory decrease in cholinesterase activity. Age‐related changes in purinergic relaxation were qualitatively similar to nitrergic relaxation although the relaxations were much smaller. Increasing age did not alter the response of the anorectum smooth muscle to exogenously applied ACh, ATP, sodium nitroprusside or KCl. Similarly, there was no change in basal tension developed by the anorectum.Conclusions and InferencesThe decrease in nitrergic signaling with increasing age may contribute to the age‐related fecal impaction and constipation previously described in this model by partially obstructing defecation.

Highlights

The anorectum of the mouse consists of the internal anal sphincter (IAS) and distal most portion of the rectum.[1]
We examined whether the age-related changes in the L-NG-Nitroarginine; NG-nitro-L-Arginine (L-NNA)- sensitive component of the relaxation were due to changes in nitric oxide release or the sensitivity of the smooth muscle cells to sodium nitroprusside (SNP)
This study investigated the effects of increasing age on the basal tone and cholinergic, purinergic and nitrergic signaling in the mouse

Summary

| INTRODUCTION

The anorectum of the mouse consists of the internal anal sphincter (IAS) and distal most portion of the rectum.[1]. Contraction of the mouse IAS and anal pressure is maintained predominantly through the spontaneous contraction of the IAS circular muscle, and through the activity of excitatory cholinergic motor neurons.[9,10] Previous work has shown that the young murine IAS contracts following stimulation of excitatory cholinergic neurons, the release of acetylcholine (ACh) and activation of both M2. The study used a combination of classical organ bath assays and pharmacology to measure IAS function and sensors to detect the overflow of both NO and ACh from the IAS smooth muscle

| Ethical approval

Key Points

Findings

| DISCUSSION