The actions of nitric oxide donors in the prevention or induction of injury to the rat gastric mucosa
1993
1
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.
2
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.
3
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.
4
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.
5
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.
6
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.
7
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.
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