Chronic cyclosporine A treatment reduces prostaglandin E2 formation in isolated glomeruli and papilla of rat kidneys.

Abstract

Immunoreactive prostaglandin E2 (PGE2) formation of rat renal papilla and isolated glomeruli was determined following chronic cyclosporine A treatment (25 and 50 mg/kg BW/daily for up to 6 weeks). Additionally, the in vitro production of PGE2 and the release of C14-labelled arachidonic acid (AA) products were evaluated in the presence of increasing doses of cyclosporine A (CyA). Renal papillary slices and glomeruli were incubated in Krebs-Ringer-Buffer (KRB) at 37 degrees C under air conditions. PGE2 and C14-labelled AA-metabolites were determined in the incubation medium. Chronic in vivo CyA treatment reduced in vitro renal papillary PGE2 formation significantly. Furthermore, the conversion of AA to PGE2 by isolated glomeruli was significantly lower in rats pretreated with CyA over three weeks. In addition, the stimulatory effect of furosemide on PGE2 formation by isolated glomeruli was impaired following an in vivo CyA treatment for three weeks. In vitro incubation of CyA with renal papilla had no effect on in vitro PGE2 formation or the release of C14-labelled AA-metabolites. The data demonstrate that chronic in vivo treatment with CyA can reduce renal PGE2 formation. This effect might influence PG mediated renal functions.