Repeated administration of
indomethacin delays the healing of
acetic acid-induced
gastric ulcers in rats, but the underlying mechanism remains unclear. We examined the effect of
indomethacin on the contraction of the connective tissue isolated from the base of 1-week-old
ulcers. The tissue samples, suspended in an organ bath, were contracted by
serotonin,
bradykinin and
carbachol and also slightly contracted by
prostaglandin (PG) F1 alpha. The effect of
serotonin was the most potent. However,
6-keto-PGF1 alpha,
PGE2 and
histamine had little or no contraction inducing effect. The contractile response to
serotonin of the tissue in the
indomethacin-treated group was significantly less than that in the control group (without
indomethacin treatment). After a 2-week treatment with
indomethacin, a histological study of the
ulcers showed that the length of rupturing of the muscularis mucosa was significantly greater than that observed in the control group. However,
indomethacin had no effect on the length of the regenerated mucosa and the thickness of the
ulcer base. We conclude that the connective tissue at the
ulcer base has the ability to contract and that the prevention of the contraction of the tissue by
indomethacin might be involved in the mechanism underlying delayed
ulcer healing.