Nitric oxide: Relation to integrity, injury, and healing of the gastric mucosa

Abstract

Nitric oxide (NO) plays a multifaceted role in mucosal integrity. The numerous functions of NO and the double-edged role played by NO in most of them provide a great complexity to the NO action. The three enzymatic sources of NO, neuronal NO-synthase (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS), have been characterised in the gastrointestinal tract. The protective properties of the NO derived from constitutive NO-synthases (eNOS and nNOS) have already been well established. Less clear is the role assigned to iNOS. The simplistic initial view of low levels of NO synthesised by constitutive NOS being protective while exaggerated NO levels after iNOS induction leading irremediably to cytotoxicity is being questioned by new evidence. As initially reported for constitutive NOS, iNOS activity may be associated to reduced leukocyte-endothelium interaction and platelet aggregation as well as protection of mucosal microcirculation. Moreover, iNOS activity may be important to resolve inflammation by increasing apoptosis in inflammatory cells. It is entirely possible that a low level of expression of iNOS will reflect a positive host-defense response to challenge, but that exaggerated or uncontrolled expression of iNOS itself becomes detrimental. There is no doubt about the protective role of NO in physiological conditions. However, when the mucosa is threatened, the role of NO becomes multiple and the final effect will probably depend on the nature of the insult, the environment involved, and the interaction with other mediators.

Effect of Oral TGF-Α Formulations on ASA Induced Duadenal Ulcer and The Role of Lipid Peroxidation in The Healing Process

“…The ability of endogenous NO to protect the mucosa is effective against a wide variety of damaging agents. Moreover, NO acts as the endogenous mediator for the gastroprotective actions of different antiulcer agents, several hormones and modulators of neural activity [14]. In the present study NOx levels increased significantly in the ME containing TGF-α treated groups (Figure 4) while the ulcer areas decreasing.…”

“…Cooperation between NO and prostaglandins in gastroprotection was reported previously [13]. In particular, NO interacts with neuropeptides and prostaglandins to maintain mucosal integrity in basal conditions [14]. The release of NO in the ulcerated mucosa contributes to tissue repair as demonstrated by the fact that treatment with NOS inhibitors delays such a process [15].…”

“…The release of NO in the ulcerated mucosa contributes to tissue repair as demonstrated by the fact that treatment with NOS inhibitors delays such a process [15]. In basal conditions, nitric oxide (NO) plays an important regulatory role in maintaining gastric mucosal integrity via interacting with neuropeptides and prostaglandins [14]. The release of NO in the ulcerated mucosa contributes to tissue repair as demonstrated by the fact that treatment with NOS inhibitors delays such a process [15].…”

Protective effect of Acer mono Max. sap on water immersion restraint stress-induced gastric ulceration

“…Previous studies have revealed that WIRE stress-induced gastric mucosal damage involves increased gastric juice secretion, gastric peristalsis, gastrocirculation disturbances in mucosal tissues, reduced prostaglandin levels, low turnover of gastric mucosa and NO-induced changes in gastric mucus cells (23)(24)(25). Among these patterns, NO-mediated regulation is particularly important as it is associated with host defense and inflammatory responses (26) and also plays a pivotal role in gastric mucosal protection against damage induced by ethanol, stress, endotoxins and drugs (27). NOS activity is particularly high in gastric tissues (28), where NO helps maintain gastric tissue integrity (29), controls gastromucosal-derived blood flow (30) and increases gastric mucus synthesis and secretion (28).…”

Gastrodia elata Blume protects against stress-induced gastric mucosal lesions in mice

“…Previous studies have shown that WIR-induced gastric mucosal lesions are associated with increased gastric acid production, accelerated gastric peristalsis, microcirculation disturbances in the gastric mucosa, decreased prostaglandin levels, low turnover of gastric mucous cells, and NO-mediated changes in the homeostatic functions of the gastric mucosa (20)(21)(22). Of these mechanisms, NO-mediated regulation is particularly important, as it is involved in host defense and inflammatory responses (23), and also plays a critical role in gastric mucosal protection against injury induced by pressure, ethanol, stress and/or endotoxins (24). NOS activity is particularly high in gastric tissue (25), where NO helps maintain the integrity of the gastric epithelium (26), regulates gastric mucosal blood flow (27), and stimulates gastric mucus secretion and synthesis (25).…”