Gastric prostacyclin (PGI2) prevents stress-induced gastric mucosal injury in rats primarily by inhibiting leukocyte activation.
We investigated whether, in rats, gastric prostacyclin (PGI2) prevented gastric mucosal injury that was induced by water-immersion restraint stress by inhibiting leukocyte activation. Gastric levels of 6-keto-PGF1alpha, a stable metabolite of PGI2, increased transiently 30 min after stress, followed by a decrease to below the baseline 6-8 h after stress. Gastric mucosal blood flow decreased to approximately 40% of the baseline level 8 h after stress. Myeloperoxidase activity was significantly increased 8 h after stress. Treatment with indomethacin before stress inhibited the increase in 6-keto-PGF1alpha levels and markedly reduced mucosal blood flow. It also markedly increased leukocyte accumulation and mucosal lesion formation. Iloprost, a stable PGI2 analog, inhibited the indomethacin-induced decrease in mucosal blood flow, mucosal lesion exacerbation, and increase in leukocyte accumulation. Nitrogen mustard-induced leukocytopenia inhibited the indomethacin-associated lesion exacerbation and the increase in leukocyte accumulation, but not the decreases in mucosal blood flow. These observations indicate that gastric PGI2 decreases gastric mucosal lesion formation primarily by inhibiting leukocyte accumulation.
Harada
N
N
Department of Laboratory Medicine, Kumamoto University School of Medicine, Honjo, Japan.
Okajima
K
K
Murakami
K
K
Isobe
H
H
Liu
W
W
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D011464:Epoprostenol / Q000378:metabolism*; D005753:Gastric Mucosa / Q000098:blood supply / Q000293:injuries / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007962:Leukocytes / Q000378:metabolism*; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008466:Mechlorethamine / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013312:Stress, Physiological / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008466:Mechlorethamine; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D009195:Peroxidase; D007213:Indomethacin