Expression of endothelial cell-derived nitric oxide synthase (eNOS) is increased during gastric adaptation to chronic aspirin intake in humans.
BACKGROUND
Gastric adaptation to aspirin is well-documented. However, the mechanisms underlying the reduction of aspirin-induced mucosal damage despite continued ingestion of the drug remain poorly understood.


METHODS
Eight healthy volunteers who received aspirin 1 g b.d. for 14 days were compared with eight placebo-dosed controls. Gastroscopy with mucosal biopsy was performed, and gastric mucosal blood flow was measured before and following 3, 7 and 14 days of aspirin treatment. At the same time points, tissue concentration and the content of prostaglandin E2 in the gastric juice were determined and expression of endothelial cell-derived nitric oxide synthase (eNOS) in mucosal biopsies was measured using Western blot analysis.


RESULTS
Aspirin-induced mucosal damage that reached a maximum on day 3, declining significantly by day 14. Concomitantly, mucosal blood flow significantly increased on day 3 and returned to initial values on day 14. Aspirin intake led to a significant decrease in prostaglandin E2 concentration in the gastric mucosa and in gastric juice during the whole period of aspirin consumption. eNOS expression started to increase on day 7 in oxyntic mucosa and on day 3 in antral mucosa, reaching its highest values at the end of the consumption of aspirin.


CONCLUSIONS
The human gastric mucosa adapts to prolonged aspirin intake, and this is accompanied by an increase in mucosal blood flow and reduced prostaglandin synthesis. Increase of mucosal eNOS expression might compensate for reduced prostaglandin synthesis and be responsible for gastric adaptation to chronic aspirin intake in humans.
Fischer
H
H
Medizinische Klinik und Poliklinik B, Westfälische Wilhelms-Universität Münster, Münster, Germany.
Becker
J C
JC
Boknik
P
P
Huber
V
V
Lüss
H
H
Neumann
J
J
Schmitz
W
W
Domschke
W
W
Konturek
J W
JW
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004724:Endoscopy; D004727:Endothelium / Q000201:enzymology; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D012039:Regional Blood Flow; D013270:Stomach / Q000187:drug effects* / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019001:Nitric Oxide Synthase; D015232:Dinoprostone; D001241:Aspirin