Effect of E-type prostaglandins on bradykinin-induced plasma extravasation in the knee joint of the rat

Abstract

We studied the effect of different E-type prostaglandins on an experimental model of inflammation in the rat. Plasma extravasation was induced in the knee joint of the rat by continuous perfusion of two potent inflammatory mediators, bradykinin (160 nM) or platelet activating factor. Both prostaglandin E 1 and prostaglandin E 2 (0.5–500 ng ml −1), when perfused with bradykinin, produced a similar dose-dependent enhancement of plasma extravasation. Prostaglandin E 2 (0.5–500 ng ml −1) also dose dependently enhanced plasma extravasation induced by platelet activating factor, while prostaglandin E 1 significantly enhanced platelet activating factor-induced plasma extravasation only at concentrations above 5 ng ml −1. In contrast, co-perfusion of bradykinin or platelet activating factor with the prostaglandin E 1 analogues, enisoprost and misoprostol (0.5–500 ng ml −1) did not enhance plasma extravasation. In fact, misoprostol attenuated plasma extravasation induced by bradykinin. These results demonstrate that in the rat knee joint, misoprostol and enisoprost have different pharmacological actions compared to their parent compound, prostaglandin E 1 and to prostaglandin E 2.