The role of renal metabolism of PGE2 in determining its activity as a renal vasodilator in the dog.
Since the mammalian renal cortex avidly metabolizes prostaglandin E2 (PGE2), we examined the importance of renal metabolism of PGE2 in determining its renal vascular activity in the dog. We used 13, 14 dihydro PGE2 (DHPGE2) as a model compound to study this because DHPGE2 retains similar activity to the parent prostaglandin, PGE2, but is a poorer substrate than PGE2 for both the metabolism and the cellular uptake of the prostaglandins. Using dog renal cortical slices, we found that under similar experimental conditions, PGE2 was metabolized several-fold faster than DHPGE2. Both prostaglandins were metabolized to the 15 keto 13, 14 dihydro PGE2, which was positively identified using GC-MS. In vivo, we infused increasing concentrations of DHPGE2 into the renal artery of dogs and measured renal hemodynamic changes using radioactive microspheres. DHPGE2 was a potent renal vasodilator beginning at an infusion rate of 10(-9)g/kg/min. When compared to PGE2, DHPGE2 was about 10 times more potent in affecting renal vasodilation. The intrarenal redistribution of blood flow towards the inner cortex seen with DHPGE2 was identical to that seen with PGE2. We conclude that renal catabolism of PGE2 is very important in limiting the in vivo biological activity of PGE2, but regional differences in metabolism of PGE2 within the cortex are an unlikely determinant of the pattern of redistribution of renal blood flow.
D000818:Animals; D004285:Dogs; D007261:Infusions, Intra-Arterial; D007672:Kidney Cortex / Q000098:blood supply / Q000378:metabolism*; D013058:Mass Spectrometry; D011458:Prostaglandins E / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D014563:Urodynamics / Q000187:drug effects; D014665:Vasodilator Agents
D011458:Prostaglandins E; D014665:Vasodilator Agents