The neuromuscular control of human internal anal sphincter smooth muscle: The role of nitric oxide

The internal anal sphincter is a smooth muscle collar which encircles the anal canal. It plays a crucial role in continence and augmenting its activity by pharmacological means could diminish faecal leakage in patients suffering from anorectal incontinence. Such advances however, are only likely if we understand its behaviour, particularly the mechanisms which sub serve contraction and relaxation. The experiments described here examine the role of nitric oxide, a novel neurotransmitter, in human internal anal sphincter smooth muscle relaxation. Isometric tension recording of isolated strips of internal anal sphincter smooth muscle in vitro, reveals that nitric oxide is involved in neurogenic relaxation in this tissue because such relaxations are (i) mimicked by application of exogenous nitric oxide; (ii) inhibited by antagonists of nitric oxide synthase, the enzyme which catalyses the synthesis of nitric oxide and; (Hi) inhibited by oxyhaemoglobin, which scavenges extracellular nitric oxide. A neuronal source for nitric oxide within the hum an internal anal sphincter is suggested by the presence in this tissue of nerves which contain nitric oxide synthase. It is likely that these play a key role in anorectal function because their distribution and morphology is consistent with them mediating the rectoanal inhibitory reflex. They descend from cell bodies which lie within rectal myenteric ganglia and their appearance suggests that they are inhibitory motor neurones within the gut. Such nerves are absent in Hirschsprung's disease, a condition in which the reflex can not be demonstrated. The importance of nitric oxide in human internal anal sphincter smooth muscle activity is further emphasised by the demonstration that in vitro, it mediates relaxation of this tissue in response to muscarinic cholinoceptor stimulation. These results indicate that nitric oxide is an important mediator in the control of hum an internal anal sphincter smooth muscle