Basal internal anal sphincter tone, inhibitory neurotransmission, and other factors contributing to the maintenance of high pressures in the anal canal

Abstract

Maintenance of the basal tone in the internal anal sphincter (IAS) is critical for rectoanal continence. Effective evacuation requires a fully functional rectoanal inhibitory reflex (RAIR)-mediated relaxation of the IAS via inhibitory neurotransmission (INT). Systematic studies examining the nature of the INT in different species have identified nitric oxide (NO) as the major inhibitory neurotransmitter. However, other mediators such as vasoactive intestinal polypeptide (VIP), ATP, and carbon monoxide (CO) may also play species-specific role under certain experimental conditions. Measurements of the intraluminal pressures in the IAS along with the force of the isolated IAS tissues are the mainstay in the basic studies for the molecular mechanisms underlying the basal tone and in the nature of the INT. The identification of NO as the inhibitory neurotransmitter has led to major advances in the diagnosis and treatment of a number of rectoanal motility disorders associated with the IAS dysfunction. Besides the IAS, the high pressures in the anal canal are affected by the external anal sphincter (EAS) function, and its malfunction may also lead to rectoanal incontinence. Different approaches including biofeedback have been attempted to improve the EAS function, with variable outcomes. There is a dire need for the innovative ways to improve the week high pressures zone in the anal canal. This viewpoint focuses on two studies that extend the above concept of multiplicity of inhibitory neurotransmitters1, and that high pressures in the anal canal can be improved by the EAS plication.2

C-type atriuretic peptide causes relaxation of the internal anal sphincter through natriuretic peptide receptor B

“…The IAS tone is altered by neural and humoral signals through various membrane receptors [20,29]. The present study showed that NPR-B mediated relaxation in the IAS, which plays an important role in maintaining continence.…”

Main Manometric Findings and Potential for Anorectal Physical Therapy in the Treatment of Patients With Evacuation Disorders

“…The real effect of aBF on HPZ needs further investigation, however, striated muscle fibers such as those seen in the external anal sphincter, levator ani and puborectalis may contribute to the pressures found in HPZ. Therefore, the benefit of aBF observed in individuals with FI can, in part, be explained by the stimulation of these muscle groups and the consequent tonus improvement in the high-pressure zone (18) .…”

Differential expression of multidrug resistance protein 5 and phosphodiesterase 5 and regulation of cGMP levels in phasic and tonic smooth muscle

“…In both phasic and tonic muscle, phosphorylation of MLC 20 is a prerequisite for contraction; the levels of MLC 20 phosphorylation are determined by the opposing activities of MLCK and MLC phosphatase, and both of these enzymes' activities are well regulated in smooth muscle. Although MLCK-mediated contraction is strictly dependent on intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ), agonist-induced MLC 20 phosphorylation and contraction can be maintained even after [Ca 2ϩ ] i returns to basal levels via two ways: MLC 20 phosphorylation by Ca 2ϩ -independent MLCKs and regulated inhibition of MLC phosphatase (12,30,38,43).…”

“…The underlying features of phasic muscles (e.g., distal stomach and intestine) are the ability to generate rhythmic contractions and relaxations, whereas tonic muscles (e.g., sphincters and proximal stomach) have sustained tone and relax transiently in response to relaxant transmitters (4,23,30,38). In both phasic and tonic muscle, phosphorylation of MLC 20 is a prerequisite for contraction; the levels of MLC 20 phosphorylation are determined by the opposing activities of MLCK and MLC phosphatase, and both of these enzymes' activities are well regulated in smooth muscle.…”