PMID: 2499734Jun 1, 1989Paper

Cyclosporine inhibits endothelial cell prostacyclin production

The Journal of Surgical Research
R A RosenthalK U Kahng

Abstract

Cyclosporine (CsA)-induced alterations in endothelial production of prostacyclin (PGI2) may be a contributing factor to the decreased renal blood flow and glomerular thromboses associated with CsA nephrotoxicity. This study was performed to determine the effects of clinically relevant doses of CsA on arachidonic acid-stimulated production of PGI2 by cultured human vein endothelial cells (HUVEC). Confluent monolayers of HUVEC were incubated at 37 degrees C under 5% CO2/95% air for 15 min in Hanks'/Hepes buffer containing 0.01-5.0 microM CsA in 0.01% absolute alcohol. PGI2 production was then stimulated by the addition of 20 microM arachidonic acid and further incubation for 15 min. Supernatants were assayed for 6-keto-PGF1 alpha by radioimmunoassay. The results of this experiment indicate that CsA had a dose-dependent effect on arachidonic acid-stimulated PGI2 production by HUVEC which varied linearly with the log of the dose (r = -0.48, P = 0.003). Concentrations of 0.01, 0.05, and 0.1 microM were stimulatory and 0.5, 1.0, and 5.0 microM were inhibitory. Separate experiments demonstrated that 0.1-5.0 microM CsA had no effect on cell viability (trypan blue exclusion) or growth. These results indicate that CsA inhibits arachidoni...Continue Reading

References

Sep 15, 1987·Biochemical and Biophysical Research Communications·A KurtzK M Koch
Jun 1, 1987·Canadian Journal of Physiology and Pharmacology·L GirouxP Daloze
Dec 1, 1987·Kidney International·A A GraceP Dandona
Nov 15, 1983·Thrombosis Research·G H NeildD G Williams

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Citations

Sep 1, 1990·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·J Mason
Nov 12, 2003·Pharmacology & Therapeutics·Farzad Moien-AfshariIsmail Laher
Jun 24, 1998·Transplantation Proceedings·S MilliardP Daloze
Feb 6, 2009·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Bente JespersenBoye L Jensen
Jan 1, 2010·Mediterranean Journal of Hematology and Infectious Diseases·Evi Stavrou, Hillard M Lazarus
Oct 1, 1990·The Journal of Surgical Research·R A Rosenthal, V H Ocasio
Apr 20, 2010·JACC. Cardiovascular Interventions·Raymond J Zimmer, Michael S Lee
Dec 20, 2014·Biomarkers in Medicine·Mangalee FernandoZoltan H Endre
Nov 20, 2002·Bone Marrow Transplantation·A S DalyJ H Lipton

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