Cyclosporin A and renal prostaglandin biosynthesis.
The effect of cyclosporin A (CyA) treatment of rats on prostaglandin synthesis in the renal cortex was studied. Renal cortical slices were prepared from control and CyA-treated rats and the release of prostaglandins into the medium during incubation at 37 degrees was measured. Rats killed 4 hours after receiving 100 mg/kg CyA orally showed no changes in renal slice release of PGE2, PGF2 alpha, 6-keto-PGF1 alpha or thromboxane B2. The slice release of 6-keto-PGF1 alpha was tested after 5 days of CyA treatment and again there was no difference from control rats. The effect of CyA added to slice incubations in vitro was examined: CyA had no effect on PGE2 or 6-keto-PGF1 alpha release in the presence or absence of angiotensin II. Under all of these experimental conditions there was evidence of CyA-induced stimulation of the renin-angiotensin system. Indomethacin treatment did not inhibit CyA-mediated accumulation of renin in the renal cortex. The results suggest that renal prostaglandins do not play a role in CyA-stimulated renin storage or release, or in CyA nephrotoxicity.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology*; D015232:Dinoprostone; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D050356:Lipid Metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000378:metabolism; D051381:Rats; D011920:Rats, Inbred WF; D012083:Renin / Q000378:metabolism
D003524:Cyclosporins; D011453:Prostaglandins; D011458:Prostaglandins E; D015121:6-Ketoprostaglandin F1 alpha; D012083:Renin; D015232:Dinoprostone; D007213:Indomethacin