Indomethacin, but not Helicobacter pylori, inhibits adaptive relaxation in isolated guinea-pig stomach.
Nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (H. pylori) are major factors in gastritis and peptic ulcer However, the role of NSAIDs and H. pylori infection in dyspepsia remains unclear. Gastric adaptive relaxation may be related to the pathogenesis of functional dyspepsia because the response is often disturbed in dyspeptic patients. In this study, we investigated the effects of indomethacin or H. pylori water extracts on gastric adaptive relaxation. This experiment was performed using the modified method of Desai et al. Isolated guinea-pig stomach in an organ bath was monitored for intragastric pressure and volume. Adaptive relaxation was induced by gastric luminal distention. The effects of indomethacin and H. pylori on gastric relaxation were tested in this system. Indomethacin (> 1 x 10(-5) M) significantly inhibited adaptive relaxation. Indomethacin (> 3 x 10(-6) M) induced gastric relaxation in a dose-dependent fashion. However, aspirin at a concentration sufficient for cyclooxygenase (COX)-1 inhibition did not induce gastric relaxation. Preincubation with N-nitro-L-arginine methyl ester, a nitric oxide (NO)-synthase inhibitor, inhibited indomethacin-induced gastric relaxation. Adaptive relaxation was not affected by H. pylori water extracts. In conclusion, indomethacin inhibited adaptive relaxation via prior gastric relaxation. NO production, but not COX-1 inhibition, may be involved in this effect of indomethacin. H. pylori water extracts may not have direct effects on adaptive relaxation. Inhibition of adaptive relaxation may be one of the major mechanisms underlying NSAID-induced dyspepsia.
Higuchi
K
K
Department of Gastroenterology, Graduate School of Medicine, Osaka City University, Osaka, Japan. khiguchi@med.osaka-cu.ac.jp
Tominaga
K
K
Watanabe
T
T
Uno
H
H
Shiba
M
M
Sasaki
E
E
Tanigawa
T
T
Takashima
T
T
Hamaguchi
M
M
Oshitani
N
N
Matsumoto
T
T
Iwanaga
Y
Y
Fukuda
T
T
Fujiwara
Y
Y
Arakawa
T
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D016480:Helicobacter pylori / Q000302:isolation & purification; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D013270:Stomach / Q000187:drug effects* / Q000382:microbiology* / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007213:Indomethacin