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. 1993 Jan;108(1):73–78. doi: 10.1111/j.1476-5381.1993.tb13442.x

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

J Lopez-Belmonte 1, B J Whittle 1, S Moncada 1
PMCID: PMC1907717  PMID: 8428217

Abstract

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 micrograms kg-1 min-1) which liberates NO on metabolic transformation, or the nitrosothiol, S-nitroso-N-acetyl-penicillamine (SNAP, 2.5-10 micrograms kg-1 min-1) which spontaneously liberates NO. 3. Local infusion of higher doses of SNAP (20 and 40 micrograms 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 micrograms 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 micrograms 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.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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