Differences in contractile properties of anorectal smooth muscle and the effects of calcium channel blockade

Background: Pharmacological manipulation of the anal sphincter is hampered by a lack of specificity. This study aimed to determine differences in the role of intracellular and extracellular calcium in the development of tone and agonist-induced contractions between internal anal sphincter (IAS) and rectal circular muscle which might allow targeted manipulation. Methods: Smooth muscle strips from the IAS and-rectal circular muscle of 24 Large White pigs were mounted for isometric tension recording in a superfu sion organ bath in the presence of different perfusates. Results: IAS developed tone and spontaneous activity that were abolished by nifedipine, which also reduced contractions to noradrenaline to 72 per cen t of control values. Rectal smooth muscle developed spontaneous activity bu t no tone. Nifedipine abolished the activity and reduced contractions to ca rbachol to 17 per cent of control. Contractile activity was abolished in bo th tissues in calcium-free solution. Transient exposure to a high calcium c oncentration reloaded the stores, and the ability of agonists to release st ored calcium was tested after 3 min in calcium-free solution. In IAS, norad renaline contraction was 76 per cent of control and in rectal circular musc le carbachol contraction was 57 per cent of control. Store loading was prev ented by nifedipine in rectal smooth muscle but not IAS. Cyclopiazonic acid reduced store filling in both tissues. Conclusion: Agonist-induced contraction of IAS is largely due to release of stored calcium and L-type calcium channels are not needed for store fillin g. Rectal circular smooth muscle depends more on extracellular calcium and uses L-type calcium channels for agonist-induced contraction and store fill ing. These differences suggest that targeted manipulation may be possible i n patients with anorectal disorders.