Role of neutrophils and mucosal blood flow in gastric adaptation to aspirin.
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.
Konturek
S J
SJ
Institute of Physiology, University Medical School, Krakow, Poland.
Brzozowski
T
T
Stachura
J
J
Majka
J
J
D000222:Adaptation, Physiological; D000284:Administration, Oral; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage / Q000633:toxicity*; D002211:Capsaicin / Q000494:pharmacology; D003714:Denervation; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D007975:Leukotriene B4 / Q000096:biosynthesis; D009475:Neurons, Afferent / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow
D011453:Prostaglandins; D007975:Leukotriene B4; D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D001241:Aspirin; D002211:Capsaicin