A comparison of anti-inflammatory and other compounds on the spontaneously contracting pregnant rat uterus

Abstract

The use of tissue from the 17 to 21 day pregnant rat uterus was based on earlier experiments showing that locally produced prostaglandins are the mediators of the spontaneous contractions in the pregnant rat uterus. The isolated uterine tissue provides a simpler method for screening compounds for inhibition of prostaglandin synthetase activity than the biochemical assays or the rat-paw-edema technique. This preparation was studied as a screening method for new antiinflammatory compounds. A 4-5 cm length of tissue from the uterus of 17-21 day pregnant Fullinsdorf rats was suspended in Kreb's bicarbonate solution and gassed with 5% carbon dioxide in oxygen. After 30 minutes to equilibrate, regular spontaneous contractions were recorded up to 8 hours. The sensitivity of this preparation to antiinflammatory agents was 10-100 times lower than reported by some others. Substances tested included papaverine, ketamine, isoprenaline, chloropromazine, desipramine, diazepam, and procaine. Only chlorpromazine had antiinflammatory activity as indicated by the ability to prevent carageenan-induced edema of the rat paw. Low concentrations of papaverine, ketamine, and isoprenaline initially reduced the force but increased the rate of contractions while chlorpromazine, desipramine, and diazepam decreased the force without affecting the rate of contraction. The known potent antiinflammatory agents, iodomethacin, phenylbutazone, acetylsalicyclic acid, and flufenamic acid reduced both rate and force of contractions of the preparation. Contractions of the preparations were completely inhibited by high doses of all these compounds. Results suggest that although isolated pregnant rat uterine tissue is a simple technique for detecting compounds that inhibit prostaglandin synthetase activity, there is lack of specificity of the preparation. Some compounds, e.g., indomethacin, have other independent effects on smooth muscle tissue.