Dexamethasone increases eNOS gene expression and prevents renal vasoconstriction induced by cyclosporin

Cyclosporin A (CsA)-induced renal vasoconstriction (RV) is attributed to an imbalance in vasoactive factors release. Dexamethasone (Dex) exerts a rena l vasodilatory effect by a mechanism not yet characterized. This study eval uates whether the effect of Dex is mediated by NO and whether it prevents C sA-induced RV. Micropuncture studies were performed in six groups of uninep hrectomized rats treated for 7 days with the following: vehicle (Veh); Veh + 4 mg/kg dexamethasone (Veh + Dex); 30 mg/kg CsA; CsA + Dex; vehicle + 10 mg/kg nitro-L-arginine methyl ester (Veh + L-NAME); and Veh + Dex + L-NAME. NO synthase (NOS) isoform mRNA levels were evaluated in renal cortex and m edulla by semiquantitative RT-PCR analysis in the first four groups. Dex pr oduced renal vasodilation, which was blocked by concomitant L-NAME administ ration, and the effect of Dex was associated with higher cortical and medul lary endothelial NOS (eNOS) and cortical inducible NOS (iNOS) mRNA levels. In the CsA group, Dex prevented RV, restoring glomerular hemodynamics to co ntrol values. These changes were associated with further enhancement of eNO S and restoration of medullary iNOS and neuronal NOS (nNOS) expression. We conclude that Dex prevents CsA-induced RV, and its vasodilator effect could be mediated by increased intrarenal generation of NO, secondary to enhance d expression of eNOS and iNOS.