Elimination from the circulation of cats of 6-keto-prostaglandin E1 compared with prostaglandins E2 and I2

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Abstract
6-keto-PGE1, when injected intravenously (i.v.) or into the aortic arch of cats, produced similar dose-dependent decreases in mean arterial blood pressure. The hypotensive effect of PGI2 was slightly less pronounced compared with that of 6-keto-PGE1, but was equally potent after i.v. and intra-arterial administration. PGE2 had a more potent depressor effect than the two other compounds when injected into the aortic arch, but was much less effective after i.v. injection. Plasma concentrations of 6-keto-PGE1, 6-keto-PGF1α and PGE2 were measured by radioimmunoassay after bolus injections of 6-keto-PGE1, PGI2 and PGE2. The half-life (t 1/2) of the initial rapid decrease in immunoreactivity, indicating the rate of elimination, was found to be 1˙04-2˙19 min for 6-keto-PGE1, 1˙16-2˙01 min for PGI2 and 0˙29-1˙08 min for PGE2. We have confirmed in the cat that 6-keto-PGE1, like PGI2 but unlike PGE2, is not substantially inactivated by the lungs and thus could act as a circulating hormone. However, despite its higher chemical stability, the t 1/2 of 6-keto-PGE1 in the circulation is similar to that of PGI2. PGE2 has a shorter t 1/2, probably due to its extensive pulmonary inactivation. Thus 6-keto-PGE1 seems to be removed from circulation as quickly as PGI2 by organs other than the lung and is unlikely to mediate prolonged effects of PGI2 in the systemic circulation.