Inducible and neuronal nitric oxide synthase involvement in lipopolysaccharide-induced sphincteric dysfunction

Abstract

We examined the effect of endotoxin lipopolysaccharide (LPS) on the basal tone and on the effects of different stimuli and agonists and transcriptional and translational expression of nitric oxide (NO) synthase (NOS) isozymes in the lower esophageal sphincter (LES), pyloric sphincter (PS), and internal anal sphincter (IAS). NO release was also examined before and after LPS. LPS caused a dose-dependent fall in the basal tone and augmentation of the relaxation caused by nonadrenergic, noncholinergic (NANC) nerve stimulation in the LES and IAS. In the PS, LPS had no significant effect on the basal tone and caused an attenuation of the NANC relaxation and an augmentation of the contractile response of muscarinic agonist. Interestingly, the smooth muscle relaxation by atrial natriuretic factor was suppressed in the LES and IAS but not in the PS. These changes in the sphincteric function following LPS may be associated with increase in the inducible NOS (iNOS) expression since they were blocked by iNOS inhibitor L-canavanine. Augmentation of NANC relaxation in the LES and IAS smooth muscle by LPS may be due to the increased activity of neuronal NOS and NO production.

Chronic Alcohol Consumption Affects Gastrointestinal Motility and Reduces the Proportion of Neuronal NOS‐Immunoreactive Myenteric Neurons in the Murine Jejunum

“…The authors concluded that exogenous NO has a prejunctional inhibitory effect on the nitrergic component of the NANC response, resulting from a down-regulation of nNOS (De Man et al, 1995). Studies of the effect of the endotoxin lipopolysaccharide on the GI tract have associated delay in gastric emptying and intestinal transit with increased expression of inducible NOS (iNOS) (Takakura et al, 1997;Fan et al, 2001;De Winter et al, 2002). The substantial concentrations of NO which can be generated by iNOS are known to autoinhibit the constitutive forms of NOS (cNOS), which may result in a condition in which iNOS is overexpressed, while cNOS is concurrently inhibited (Schwartz et al, 1997).…”

Lipopolysaccharide Induces Cell Death in Cultured Porcine Myenteric Neurons

“…Experimental studies have shown that LPS causes delayed gastric emptying (6,7), intestinal dysmotility (7,8) and sphincteric dysfunction (9), thus unravelling its interaction with enteric nerves. The precise mechanisms behind these acute LPS-induced motor effects are, however, as yet largely unknown.…”

Nitric oxide-mediated injury of interstitial cells of Cajal and intestinal dysmotility under endotoxemia of mice

“…Gastrointestinal dysmotility under septic conditions accompanies other forms of morbidity, and results in prolonged hospitalization, increased medical costs, and an increase in mortality rate. Although several pathogenic mechanisms including local inflammation, cytokines, such as tumor necrosis factor (TNF) or interleukin-1 (IL-1), and an increase in nitric oxide (NO), have been proposed for motility disorders under sepsis (4,5,18,30), the central mechanisms of gastrointestinal dysmotility under these conditions have not been elucidated. Interstitial cells of Cajal (ICCs), which mediate input from the enteric motor nervous system to smooth muscle, are the pacemaker cells in the gastrointestinal tract (9).…”