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

Using newly develop radioimmunoassay for 6-keto-prostaglandin F1 alpha and 6,15-diketo-13,14-dihydro-prostaglandin F1 alpha, 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 F1 alpha. 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 F 1 alpha, which rapidly declined (t 1/2: 1.29-1.52 min). 6,15-diketo-13,14-dihydro-prostaglandin F1 alpha appeared with an 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 F 1 alpha again was the predominant derivative after 3 min. These data suggest that in vivo prostacyclin is mainly inactivated by the 15-hydroxy-PG-dehydrogenase-, delta 13-reductase-pathway, rather than by hydrolysis. Therefore, 6,15-diketo-13,14-dihydro-prostaglandin F1 alpha seems to be a better indicator of prostacyclin plasma levels than 6-keto-prostaglandin F1 alpha, although under certain conditions the additional determinations of this product of hydrolysis can be valuable.