Formation and elimination of prostacyclin metabolites in the cat in vivo as determined by radioimmunoassay of unextracted plasma

Abstract

Using newly developed radioimmunoassays for 6-keto-prostaglandin F1α and 6,15-diketo-13,14-dihydro-prostaglandin F1α, the plasma concentrations of these two prostacyclin derivatives were measured in anaesthetized cats. After the administration of angiotensin II, which releases prostacyclin into the circulation, concentrations of both derivatives rose simultaneously, the major immunoreactivity being 6,15-diketo-13,14-dihydro-prostaglandin F1α. Angiotensin II-induced prostacyclin release was not caused by vasoconstriction alone, since comparable vasopressor responses to noradrenaline and vasopressin were not accompanied by increases in prostacyclin plasma levels. Injection of exogenous prostacyclin resulted in a shortlasting peak of 6-keto-prostaglandin F1α, which rapidly declined (t 1 2: 1.29-1.52 min). 6,15-diketo-13,14-dihydro-prostaglandin F1α appeared with a t 1 2 of 0.48-1.38 min and was eliminated with a t 1 2 of 8.0-9.0 min. Due to its longer half-life in the circulation 6,15-diketo-13,14-dihydro-prostaglandin F1α again was the predominant derivative after 3 min. These data suggest that in vivo prostacyclin is mainly inactivated by the 15-hydroxy-PG-dehydrogenase-, Δ13-reductase-pathway, rather than by hydrolysis. Therefore, 6,15-diketo-13,14-dihydro-prostaglandin F1α seems to be a better indicator or prostacyclin plasma levels than 6-keto-prostaglandin F1α, although under certain conditions the additional determination of this product of hydrolysis can be valuable. © 1981.