A comparison of the effects of prostacyclin and 6-keto-prostaglandin E1 on renin release in the isolated rat and rabbit kidney.
A direct comparison of the relative potencies of the prostaglandins PGI2 and 6-keto-PGE1 to induce renin release was made in the isolated rat kidney, which was perfused with a synthetic medium at constant perfusion pressure. Both prostaglandins stimulated renin release in a dose-dependent manner (0.01 to 1 microM) and with equal potency. Also in the isolated rabbit kidney, PGI2 and 6-keto-PGE1 had the same potency to induce renin release at 1 microM final concentration. Following infusion of 6-keto-PGE1 a small increase of vascular resistance in the rat kidney was observed, whereas in the rabbit kidney no constrictor effect was seen. When perfusates of PGI2 or 6-keto-PGE1-infused rat kidneys were tested for antiaggregatory activity in the ADP induced aggregation of human platelets and compared with authentic standards, the results showed 6-keto-PGE1 passes the kidney essentially unchanged, whereas only 25-40% of the infused PGI2 appear in the venous perfusates, as judged from the recovery of antiaggregatory activity. Analysis of venous perfusates from 3H-PGI2 infused kidneys by high performance liquid chromatography indicates that about 25% of the infused PGI2 remains intact, a major portion of the perfused radioactivity was identified as 6-keto-PGF1 alpha by combined gas chromatography-mass-spectrometry (19). We conclude that the renin-stimulating effect of PGI2 is not secondary to its metabolism to 6-keto-PGE1, as has been suggested in the literature (8).
D000527:Alprostadil / Q000031:analogs & derivatives*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D011453:Prostaglandins / Q000494:pharmacology*; D011458:Prostaglandins E / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000378:metabolism*
D011453:Prostaglandins; D011458:Prostaglandins E; C022950:6-ketoprostaglandin E1; D011464:Epoprostenol; D012083:Renin; D000527:Alprostadil