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.