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

• Published in: British journal of pharmacology 1993-01, Vol.108 (1), p.73-78
• Main Authors: Lopez‐Belmonte, J., Whittle, B.J.R., Moncada, S.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood Pressure - drug effects; Digestive system; Endothelins - administration & dosage; Endothelins - toxicity; endothelin‐1; gastric damage; Gastric Mucosa - drug effects; glyceryl tritnitrate; Infusions, Intra-Arterial; Male; Medical sciences; Nitric oxide; Nitric Oxide - metabolism; Nitroglycerin - pharmacology; nitroprusside; Nitroprusside - pharmacology; nitrosothiols; nitrovasodilators; NO‐donors; Penicillamine - analogs & derivatives; Penicillamine - pharmacology; Pharmacology. Drug treatments; Rats; Rats, Wistar; S-Nitroso-N-Acetylpenicillamine; S‐nitroso‐N‐acetyl‐penicillamine; Vasodilator Agents - pharmacology
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1993.tb13442.x

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.