ACUTE CYCLOSPORINE-INDUCED RENAL VASOCONSTRICTION IS MEDIATED BY ENDOTHELIN-1

Background Cyclosporine causes intrarenal vasoconstriction, which may account for its nephrotoxic side effects. Plasma levels of the vasocon strictor peptide endothelin-1 are increased after cyclosporine adminis tration, and endothelin-1 has been shown to cause renal vasoconstricti on. In this study we used in vivo microscopy to investigate the role o f endothelin-1 in cyclosporine-induced vasoconstriction. Methods. Hydr onephrotic kidneys in decerebrate rats were suspended in an environmen tally controlled tissue bath with neurovascular supply intact. Interlo bular, afferent, and efferent arteriolar diameters and flow were measu red by videomicroscopy and Doppler velocimetry. Cyclosporine was added to the tissue bath, and measurements were repeated for 60 minutes. In study groups endogenous endothelin-1 was blocked by infusion of eithe r specific endothelin antiserum or an endothelin-1 receptor antagonist . Results. Cyclosporine caused constriction of the interlobular artery by 20% +/- 2% and a corresponding decrease in blood flow by 66% +/- 4 %. The afferent and efferent arterioles constricted to a similar degre e. This vasoconstriction was entirely prevented by infusion of either the endothelin antiserum or the receptor antagonist. The antagonist re agents alone had no effect on hemodynamic parameters or renal microves sel diameters. Conclusions. The acute renal vasoconstriction induced b y cyclosporine is mediated by endothelin-1. Endogenous endothelin-1 ha s little role in maintaining basal vascular tone.