Effects of endotoxin on gastric injury from luminal irritants in rats: potential roles of nitric oxide

Abstract

The expression and function of inducible nitric oxide synthase (iNOS) in the stomach is unclear. This study assessed the effects of endotoxin on rat gastric iNOS expression and its role in gastric injury from luminal irritants. In conscious rats, a 5-h treatment with intraperitoneal lipopolysaccharide (LPS; 1–20 mg/kg) dose dependently increased gastric mucosal iNOS immunoreactivity and increased gastric luminal nitrate and nitrite accumulation (Griess reaction). LPS also increased gastric luminal fluid accumulation and reduced macroscopic gastric injury from orogastric acidified ethanol. Aminoguanidine (45 mg/kg) did not prevent LPS-induced gastroprotection or gastric fluid accumulation. N G-nitro-l-arginine methyl ester increased gastric luminal fluid and caused macroscopic gastric injury when given with LPS. Using an anesthetized preparation followed by removal of luminal fluid, LPS reduced gastric mucosal blood flow and exacerbated gastric injury from either acidified ethanol or acidified taurocholate, an effect that was negated by aminoguanidine. These data indicate that in conscious rats, the gastroprotective effect of endotoxin is dependent on constitutive NOS but not iNOS activity. However, the inducible isoform participates in the ability of endotoxin to exacerbate gastric injury from luminal irritants in the anesthetized rat.

Fasting Exacerbates and Feeding Diminishes LPS-Induced Liver Injury in the Rat

“…We confirmed previous findings that LPS elicits production of both pro-and antiinflammatory cytokines that favors a pro-inflammatory response as measured by the serum IL-6/IL-10 ratio [18]. We also confirmed that this inflammatory response is accompanied by elevated levels of serum hepatocellular enzymes which we have previously shown to correlate with liver injury according to histological assessment and F-actin analysis [19,20,31,32]. In these previous studies, we also reported that LPS-induced hepatic injury was mediated, at least in part, by upregulation of hepatic COX2 and iNOS, as selective inhibition of these two proteins diminished hepatic injury from LPS [19,20,[33][34][35].…”

Gastric Mucosal Protection via Enhancement of MUC5AC and MUC6 by Geranylgeranylacetone

“…The mechanism of this protection is attributed primarily to its potent vasodilatory action, which leads to the improvement of mucosal circulation; however, excessive nitric oxide production can be toxic to gastric mucosa (53,54). The expression of iNOS was not affected by GGA itself or by ethanol-induced mucosal damage, but the expression of nNOS increased in the experimental rats at 5 hours after GGA administration, suggesting that nNOS contributes to the delayed protection afforded by GGA.…”

Geranylgeranylacetone stimulates mucin synthesis in cultured guinea pig gastric pit cells by inducing a neuronal nitric oxide synthase

“…28,29 On the other hand, the excessive production of NO can be toxic to the gastric mucosa. 30,31 NO is known to play an important role in the regulation of the synthesis and secretion of gastric mucin. [20][21][22][23] The present experiments were designed to confirm that NO stimulates mucin synthesis in gastric pit cells.…”