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Role of neutrophils and mucosal blood flow in gastric adaptation to aspirin.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 1994 Feb 21; Vol. 253 (1-2), pp. 107-14. - Publication Year :
- 1994
-
Abstract
- Gastric mucosa adapts to ulcerogenic action of aspirin but the mechanism of this phenomenon is unknown. In this study, acute gastric lesions were produced by single or repeated oral administration of acidified aspirin in rats with intact or deactivated (by capsaicin) sensory nerves and with intact or suppressed synthase of nitric oxide (NO). Single oral dose of aspirin produced a dose-dependent increase in the area of gastric lesions accompanied by a significant increase in blood neutrophils, neutrophil infiltration into the mucosa, leukotriene B4 formation and almost complete suppression of prostaglandin synthesis. After repeated administration of aspirin, the mucosal damage progressively declined and this was accompanied by a significant augmentation in gastric blood flow. In addition, a reduction in blood neutrophil count, mucosal neutrophil infiltration and leukotriene B4 release was observed during this adaptation of the stomach to repeated aspirin insults. Capsaicin denervation of sensory nerves aggravated the damage induced by the first exposure of the stomach to aspirin and caused a significant reduction in gastric blood flow, but with repeated aspirin administration, gastric adaptation to this agent and a rise in gastric blood flow were observed. Pretreatment NG-nitro-L-arginine with (L-NNA), a specific inhibitor of nitric oxide synthase, eliminated the hyperemic response to repeated aspirin insults but failed to affect the adaptation to aspirin. We conclude that the rat stomach adapts readily to repeated aspirin insults despite sustained inhibition of prostaglandin biosynthesis and this adaptation appears to be mediated by a significant increase in gastric blood flow and a reduction in neutrophil activation and leukotriene B4 release.
- Subjects :
- Adaptation, Physiological
Administration, Oral
Amino Acid Oxidoreductases antagonists & inhibitors
Animals
Arginine analogs & derivatives
Arginine pharmacology
Aspirin administration & dosage
Capsaicin pharmacology
Denervation
Female
Gastric Acid metabolism
Gastric Mucosa blood supply
Gastric Mucosa innervation
Gastric Mucosa physiology
Leukotriene B4 biosynthesis
Neurons, Afferent drug effects
Neutrophils drug effects
Nitric Oxide Synthase
Nitroarginine
Prostaglandins biosynthesis
Rats
Rats, Wistar
Regional Blood Flow
Aspirin toxicity
Gastric Mucosa drug effects
Neutrophils physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 253
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 7516882
- Full Text :
- https://doi.org/10.1016/0014-2999(94)90764-1