Antibodies to 5,6-dihydroprostaglandin I2 trap endogenously produced prostaglandin I2 in the rat circulation.

Rabbit immunoglobulins raised against 5,6-dihydroprostaglandin I2 which crossreact with prostaglandin I2 were infused intravenously into Inactin-anaesthetised male adult rats. Clearance of intravenously administered [3H]prostaglandin I2 from the blood, which is normally rapid (t 1/2 approx. 45 s), was delayed strikingly in the presence of antibody (t 1/2 approx. 60 min). The antibodies also sequestered the endogeneously synthesized prostaglandin I2 and inhibited its metabolism. The rate of appearance of endogenous prostaglandin I2 in the circulation of the rat was measured in the following way: arterial blood samples (0.5 ml) were withdrawn before, during and at various time intervals (up to 180 min) after infusion of antibodies had terminated; the prostaglandins were extracted from the blood with ethanol, and the extracts were assayed by radioimmunoassay (before and after separation by high-pressure liquid chromatography) for the following prostaglandins: 6-keto-F1 alpha, E2, F2 alpha and 13,14-dihydro-15-keto-metabolites of E2 and F2 alpha. Rapid and specific time-related increments of prostaglandin I2 (detected serologically as 6-keto-F1 alpha) were observed. At 180 min these increases ranged from 1500- to 2500-fold over preinfusion levels. No significant increases were observed in the other prostaglandins measured; nor were there increases in 6-keto-F1 alpha when saline or immunoglobulins from non-immune plasma were infused into rats. When measured by these procedures, no appreciable differences in 6-keto-F1 alpha production were found between Japanese normotensive and spontaneously hypertensive rats.