Release of prostaglandins from intact fetal lamb ductus arteriosus.

Abstract

Intact rings and slices of ductus arteriosus from fetal lambs near term (130–143 days gestation) were incubated with [14C]arachidonic acid and the fate of the label in the incubation fluid and tissue was followed by thin-layer radiochromatography (TLC). Prostaglandins formed from endogenous stores of arachidonic acid were assayed by capillary gas chromatography with electron-capture detection. In additional experiments, the prelabelled tissue was incubated with various drugs (e.g., angiotensin II, bradykinin, and calcium ionophore) to determine their effects on the release of 14C-labelled prostaglandins. Results indicate that the ductus arteriosus is oriented towards forming prostaglandin (PG) I2, with PGE2 being formed to a minor extent in all studies. While radiochromatographic studies (TLC) suggested a considerable complexity mostly because of overlapping products (PGs and metabolites), this was resolved using gas chromatography where a complete resolution of PGs from these metabolites was observed. In the tissue-labelling experiments most of the radioactivity remained in the incubation fluid and was recovered as unchanged arachidonic acid, although a small but significant proportion of label was observed in a mixture of prostaglandins (4.2 ± 0.6%, n = 16) with 6-keto PGF1α being the major product. The ductus tissue incorporated a small amount of label (3.4 ± 0.4%, n = 19) of which 49.7 ± 4.9% (n = 13) was found in the tissue phospholipids. Hydrolysis of tissue-bound [14C]arachidonic acid, which appeared in the perfusing medium together with 14C-labelled prostaglandins, was in the range of 28.0 ± 2.7% (n = 9) of total tissue radioactivity per experiment. Although 42.2 ± 2.5% (n = 18) of the radioactivity released by each of the drugs represented a mixture of prostaglandins and their metabolites (the rest recovered as arachidonic acid), no appreciable selectivity by any of the drugs was found for either the stimulation of phospholipase activity in this tissue or for the rerouting of the prostaglandin synthetic system to form prostaglandin E2 instead of I2. We conclude that prostaglandin I2 rather than E2 is probably of physiological importance in this unique fetal blood vessel.