The role of the kidney in the metabolism of prostacyclin by the 15-hydroxyprostaglandin dehydrogenase pathway in vivo

Abstract

Five different vascular beds of the cat were tested for their ability to metabolize tritium-labeled or unlabeled prostacyclin by 15-hydroxyprostaglandin dehydrogenase in vivo. Thin-layer radiochromatography with two different solvent systems was used to characterize the radioactive metabolites formed. Following the infusion of unlabeled prostacyclin, plasma levels of 6-ketoprostaglandin F 1α and 6,15-diketo-13,14-dihydroprostaglandin F 1α immunoreactivities were monitored using previously described radioimmunoassays. No important metabolism was found in the head and the hindlimb. Plasma extracts from the vascular bed of the lung (and the heart) contained only small amounts of 6,15-diketo-13,14-dihydroprostaglandin F 1α-like material. Prostacyclin was extensively metabolized in the liver (probably by β- and ω-oxidation), but no material similar to 6,15-diketo-13,14-dihydroprostaglandin F 1α was found. In renal venous blood the predominating material showed properties similar to those of 6,15-diketo-13,14-dihydroprostaglandin F 1α with both analytical methods. In other experiments aortic blood was collected during and after infusions of tritium-labeled prostacyclin into the postcava. Two consistent peaks were demonstrated in plasma extracts of this blood, one co-chromatographing with 6-ketoprostaglandin F 1α and the other one with 6,15-diketo-13,14-dihydroprostaglandin F 1α. In nephrectomized animals the formation of the 6,15-diketo-13,14-dihydroprostaglandin F 1α-like material was not significantly impaired. Similarly, no significant differences in the formation and elimination of 6,15-diketo-13,14-dihydroprostaglandin F 1α immunoreactivity and 6-ketoprostaglandin F 1α immunoreactivity were found after nephrectomy. It is concluded that, although the kidneys have a considerable capacity to metabolize prostacyclin by 15-hydroxyprostaglandin dehydrogenase, they seem to be of little importance for the overall conversion of prostacyclin via this pathway in the total circulation.