Elimination from the circulation of cats of 6-keto-prostaglandin E1 compared with prostaglandins E2 and I2.
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-PGF1 alpha and PGE2 were measured by radioimmunoassay after bolus injections of 6-keto-PGE1, PGI2 and PGE2. The half-life (t1/2) 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 t1/2 of 6-keto-PGE1 in the circulation is similar to that of PGI2. PGE2 has a shorter t1/2, 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.
D000527:Alprostadil / Q000031:analogs & derivatives*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D015232:Dinoprostone; D011464:Epoprostenol / Q000097:blood* / Q000494:pharmacology; D005260:Female; D008297:Male; D011458:Prostaglandins E / Q000097:blood* / Q000494:pharmacology; D011863:Radioimmunoassay; D013997:Time Factors
D011458:Prostaglandins E; C022950:6-ketoprostaglandin E1; D011464:Epoprostenol; D000527:Alprostadil; D015232:Dinoprostone