The actions of nitric oxide donors in the prevention or induction of injury to the rat gastric mucosa

Abstract

The protective or damaging actions on the gastric mucosa, of locally infused nitrovasodilators that donate nitric oxide (NO), have been investigated in the pentobarbitone‐anaesthetized rat. Local intra‐arterial infusion of endothelin‐1 (ET‐1; 5 pmol kg−1 min−1 for 10 min) induced extensive, macroscopically apparent, haemorrhagic injury to the rat gastric mucosa. This damage was dose‐dependently reduced by concurrent local intra‐arterial infusion of glyceryl trinitrate (GTN; 10–40 μg kg−1 min−1) which liberates NO on metabolic transformation, or the nitrosothiol, S‐nitroso‐N‐acetyl‐penicillamine (SNAP, 2.5–10 μg kg−1 min−1) which spontaneously liberates NO. Local infusion of higher doses of SNAP (20 and 40 μg kg−1 min−1, i.a.) did not, however, significantly protect against mucosal injury induced by ET‐1. Furthermore, local infusion alone of these higher doses of SNAP, as well as sodium nitroprusside (10–40 μg kg−1 min−1, i.a.) which also spontaneously liberates NO, induced significant mucosal injury, as assessed macroscopically and confirmed by histology. Local infusion of these higher doses of SNAP and nitroprusside reduced systemic arterial blood pressure (BP), but this was not correlated with the extent of mucosal injury. Furthermore, local infusion of GTN (10–40 μg kg−1 min−1, i.a.) alone, which also reduced BP, failed to induce gastric mucosal damage. These findings suggest that exogenous NO can protect the rat gastric mucosa from damage induced by the vasoconstrictor peptide ET‐1, which may reflect local microcirculatory interactions. However, the unregulated release of high levels of NO within the microvasculature induces mucosal injury.

The effect of simvastatin pretreatment on stress-induced gastric ulcer in rats

“…NO is one of the most efficient mediators of gastric defense mechanism. Previous studies have shown that gastric lesions induced by various chemical agents are attenuated by administration of NO donors or augmented by suppression of the NO pathway [35]. However, in our study, the nonselective NOS inhibitor L-NAME given alone or prior to SIM to animals with cold-restraint ulcer did not show a statistically significant effect on the severity of the gastric lesions, gastric GSH content and gastric CL levels.…”

Helicobacter pylori infection and gastric mucosal epithelial cell apoptosis

“…Another molecule -nitric oxide (NO)-has been seen to play a role in the protection of the gastric mucosa by increasing blood flow and inhibiting leukocyte adhesion to the endothelium (126). The normal gastric mucosa contains no inducible NO synthase (iNOS) enzyme, but its expression increases in patients with H. pylori-related gastritis (116).…”

Factors Associated with Nitric Oxide-mediated β2 Integrin Inhibition of Neutrophils

“…Administration of ⅐ NO donors has been shown to have benefit in abrogating ␤ 2 integrin function and neutrophil adhesion after ischemia reperfusion (6 -10). Dose response is difficult to predict, however, and ⅐ NO administration can have the opposite effect under some conditions, thus exacerbating inflammatory injuries (5,(11)(12)(13)(14)(15).…”