Regulation of gastric mucosal integrity by endogenous nitric oxide: interactions with prostanoids and sensory neuropeptides in the rat

Abstract

The interactions between nitric oxide (NO), prostacyclin and sensory neuropeptides in the maintenance of gastric mucosal integrity have been investigated in the anaesthetized rat. Administration of either NG‐monomethyl‐l‐arginine (l‐NMMA) to inhibit endothelium‐derived NO formation, indomethacin to inhibit prostanoid biosynthesis or chronic capsaicin pretreatment to deplete sensory neuropeptides, did not induce acute mucosal injury. In capsaicin‐pretreated rats, however, l‐NMMA (12.5–100 mg kg−1 i.v.) dose‐dependently induced acute mucosal damage, characterized as vasocongestion and haemorrhagic necrosis. The enatiomer d‐NMMA (100 mg kg−1 i.v.) did not induce any detectable mucosal damage. This mucosal injury induced by l‐NMMA was inhibited by concurrent administration of l‐arginine (300 mg kg‐1 i.v.). In indomethacin (5 mg kg−1 i.v.)‐pretreated rats, l‐NMMA also induced mucosal damage. Furthermore, following indomethacin administration in capsaicin‐pretreated rats, l‐NMMA induced widespread, severe haemorrhagic necrotic damage. These findings suggest a role for endogenous NO formed from l‐arginine, acting in concert with prostacyclin and sensory neuropeptides, in the modulation of gastric mucosal integrity.

Gastroprotective effects of Stachys Lavandulifolia extract on experimental gastric ulcer

“…Several studies have demonstrated the importance of endogenous NO in the protection of gastric mucosa (Kim and Kim, 1998;Tanaka et al, 2001;Whittle et al, 1990). Also endothelial NO plays an important role in the modulation of gastric mucosal integrity by interacting with sensory neuropeptides (Whittle et al, 1990;Tepperman and Whittle, 1992), reducing neutrophil adhesion and increasing gastric blood flow and mucus secretion (Souza et al, 2004). In the present study, alcohol significantly reduced gastric mucosal NO level with increase mucosal injury compared to control group.…”

“…These findings suggest that endogenous NO may participate in the regulation of gastric secretion via an intracellular signaling molecule (Dijkstra et al, 2004). Several studies have demonstrated the importance of endogenous NO in the protection of gastric mucosa (Kim and Kim, 1998;Tanaka et al, 2001;Whittle et al, 1990). Also endothelial NO plays an important role in the modulation of gastric mucosal integrity by interacting with sensory neuropeptides (Whittle et al, 1990;Tepperman and Whittle, 1992), reducing neutrophil adhesion and increasing gastric blood flow and mucus secretion (Souza et al, 2004).…”

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

“…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). L-arginine, a NOS substrate, has been shown to facilitate gastric ulcer healing by increasing cell regeneration in stomach tissues (31).…”

Investigation on the mechanisms involved in the central protective effect of amylin on gastric ulcers in rats

“…There is evidence that the NO system beside playing a role in the regulation of the gastric mucosal blood¯ow which contributes to protection against injurious agents (Sorbye & Svanes, 1994), cooperates with the prostaglandin system in the maintenance of gastric mucosal integrity (Whittle et al, 1990). Furthermore these two mediators can regulate the synthesis of one another as NO has been shown to stimulate cyclooxygenase activity (Salvemini et al, 1993).…”