Prevention and complete reversal of cyclosporine A-induced renal vasoconstriction and nephrotoxicity in the rat by fenoldopam.

The primary mechanism of cyclosporine A-induced nephrotoxicity involves renal vasoconstriction. In the present study, we have tested the effects of fenoldopam, a dopamine DA1, receptor agonist with renal vasodilator properties, on the changes in renal function induced by acute and subacute administration of cyclosporine A. In inactin-anesthetized rats, acute administration of cyclosporine A (100 mg/kg i.p.) significantly decreased paraaminohippuric acid (PAH) and inulin clearances. Fenoldopam, at a dose (10 micrograms/kg.min) which alone significantly increased PAH and inulin clearances, completely prevented the cyclosporine A-induced reductions in renal function. Similarly, subacute administration of cyclosporine A (20 mg/kg.day for 3 days) resulted in significant reductions in base-line PAH and inulin clearances which were normalized by administration of fenoldopam. These data indicate that administration of fenoldopam can both prevent and completely reverse cyclosporine A-induced renal vasoconstriction and nephrotoxicity.