Inhibition of prostaglandin synthesis and contractility in the rabbit and rat uterus by ibuprofen

Abstract

Sixty uterine strips were excised from 8 pregnant and 7 post partum rabbits and stimulated electrically in vitro until they developed maximum isometric tension. The non-steroidal anti-inflammatory agent, Ibuprofen, at concentrations of 125, 250 and 500 microng/ml, significantly reduced tension of the 55 experimental uteri (P less than 0.001) within 7.5 minutes, in comparison with the pretreatment value. Tension in 15 solvent-treated controls remained stable during the same observation period. The reduction in tension was greater in the post partum than the pregnant uteri (P greater than 0.05). Sixteen additional uterine strips, excised from 4 pregnant and 4 post partum rabbits were treated either with 500 microng Ibuprofen or solvent for 7.5 minutes. Radioimmunoassay showed that Ibuprofen significantly reduced the uterine levels of PGF (P less than 0.001) and PGE (P less than 0.001 post partum; P less than 0.05 pregnant) and again the effect was greater in the post partum uteri. These findings suggest that the suppression of uterine function by Ibuprofen is mediated by inhibition of PG-synthesis. In a subsequent study, 36 rats were treated with Ibuprofen on days 20 and 21 of pregnancy, at the ineffective dose level of 4 mg/day and the effective levels of 12, 20 and 30 mg/day. In comparison with the first group, spontaneous labor was significantly delayed in the other three groups (P less than 0.05, P less than 0.01 and P less than 0.001, respectively). In addition, 7 rats were treated with 30 mg/day Ibuprofen and 7 with solvent on days 19 and 20 of pregnancy. On day 21, the Ibuprofen-treated rats showed a significant (P less than 0.001) reduction in the uterine PGF and PGE concentrations, indicating that the prolongation of pregnancy is mediated by an inhibition of uterine PG-synthesis.